Metabolite Multiprobiotic Formulas for Microbial Health

On example of Lactobacillus and Bifidobacterium strains, approaches in creation of human multistrain probiotic metabolite mixtures for different goals were proposed. Human probiotic lectin systems (LS) (mucosal, others) reveal functions needed for organism. Advanced features of such systems include capability to recognize synthetic polymeric polyvalent glycoconjugates (GC)—imitators of natural ones (modified polysaccharides, glycoantigens of medical significance). Probiotic lectin systems function as imitators of multipro-/sym-/synbiotics in their resulting actions. They serve as carriers of the biotope glycoconjugate décor including glycoprebiotics, glycometabiotics, glycodrugs, and agents supporting décor organization and resistance. Probiotic lectin systems represent new perspective system agents to improve the health of mucosal microbiocenoses (MB) organized as communicative bodies to be corrected according to the principle “there is body—there are diseases.” They act as metabolomebiotics according to the principle “the network in the network.” They deepen biotope resistance allowing quicker return to balance. They support prophylactic and therapeutic procedures directed to prolong aging and improve quality of life. Multistrain metabolite constructions can predict perspective cellular formulas of multipro-/synbiotics for prophylaxis, supporting and accompanying therapy. Approaches developed are universal. They are useful in the study of any Gram-positive and eukaryotic (yeasts and yeast-like fungi) mono- and mixed cultures. The methodological principles proposed and described are of value for extended fields of clinical microbiology and medical bio-/nanotechnology

Interrelation between the system of complement, Tolllike receptors, CD antigens and cytokines in normal and pathological condition. Review

The overview of publications of the last five years is devoted to currently described communicative relationships between complement system, antigens of CD class, Toll-like receptors, other pattern recognition receptors and recognition molecules (interleukins, other cytokines, lectins). Studied aspects of innate immunity system actions include cooperation and synergism; adaptive strategies of microbial and viral pathogens; using probiotic microorganisms; initiation, switching, amplification and termination of key pathways in host antipathogen strategies; approaches to creation of address mechanisms of treatments of diseases at the level of metabolome network communications; prospects for constructing combinative system preparations for medicine

FUNDAMENTAL ASPECTS AND PRACTICAL PRINCIPLES OF LECTIN SYSTEMS ON THE EXAMPLE OF SYMBIOTIC MICROBIOCENOSIS STRAINS AND CONSORTIA

Prospects of lectin systems of the human biotope symbiotic microorganisms are evaluated. Symbiotic lectins are described as metabolome-biotic imitators of probiotics, carriers, deliveries, depositors, and agents realizing glycoconju-gate metabiotics. Glycoconjugate metabiotics (adequate to symbiotic lectins) represent antagonistic factors against relatively pathogenic microorganisms. Such glycoconjugates include prebiotics, therapeutic agents, décor panels currently supporting normally functioning human cells, tissues and organs. Symbiotic lectins, interacting to synthetic glycoconjugate imitators of important substances for human interactome, serve as instruments for screening strains and their consortia possessing new potential for constructing multistrain pro- and symbiotics. Algorithms of such screening and constructing based on lectins-glycoconjugates interactions are developed. Proposed anaerobic (without oxidoreductase systems participating in oxidative stress) relatively high molecular mass synergistic symbiotic lectins (in contrast to low molecular mass acidic symbiotic effectors) are perspective as network multifunctional switching assistive recognition systems functioning in agreement to human protective systems (complement, lymphocytes, macrophages) in the absence of local availability of oxygen. Results support new technological prospects of the direct and indirect resulting protection involving human intestinal indigenous symbiotic (probiotic) lectin systems against surrounding pathogenic and/or relatively pathogenic exo- and endogenic microorganisms in biotopes of organism

LECTIN-DEPENDENT DIVERSITY OF NATURAL KILLER POPULATIONS AND COMMUNICATIONS AGAINST TUMORS AND VIRUSES

Response of human natural killer (NK) cell populations (NKP) against tumors in the presence of viruses was evaluated as a quite variable, early adapting for the pathological signals in organism, mobile and selective combination agents. NKP act as a result of co-functioning between the receptor lectins (RL) recognizing glycopatterns (RL as triggers, initiators and basic agents for coupled activities), and Ig-like, cytotoxic and other additional  communicative and effector receptors (superstructural, tuning for achievement of final effector-type NKP constructions required), and their ligands (modulators of final cell surface receptor mosaics). Such NKP created play important role in redistribution of NKP-induced antitumor/ antiviral cytokines in organism. Intercellular communicative potential of NKP also involves other innate and innate-like cells. Such extended communications of NKP provide a prospective and universal resource of human protection. NKP must be under consideration upon development of new maneuvre and relilable prophylactic and immunotherapeutic antitumor/ antiviral systems and vaccine strategies. The ways for the fine tuning (RL—KIR/ NCR/ CD/ their combinations) algorithms of RL-based creation of antitumor/ antiviral NKP are revealed. Key role is given to screening spectrum of patient NKP for development of communicative anticancer/ antiviral strategies. The status of NK compartment will characterize resistance of individuum/ contingent of individuums to viral infections of epidemiological significance, will play important role in anti-epidemic protection of regional population

VISUAL PATTERNS OF С4А AND C4B SUBISOTYPES OF C4 COMPONENT OF HUMAN COMPLEMENT SYSTEM IN THE DIAGNOSTICS OF AUTOIMMUNE AND INFECTIOUS DISEASES

Results on visual patterns of subisotypes of patient sera complement component C4 complexes separated by isoelectric focusing in polyacrylamide gel and eiectrobiotting are presented. Method of visual controlled desialylation of sera using iso types C4A and C4B as internal biomarkers is described. Method was applied to investigation C4 isotyping and subisotyping patient sera. Sera of patients were classified into groups differing in subisotyping. The number of established groups of system component C4 was higher compared to groups detecting by other methods (for example, detecting using microplate functional assay of isotypes C4A and С4В]. Results open new prospects in diagnostics of autoimmune and infectious diseases using detection of pathological blood biomarkers complexed to C4 isotypes

PREDICTING SURVIVAL AND DEATH OF MICROBIAL PATHOGEN ASSOCIATES IN THE PRESENCE OF LECTINS OF PROBIOTICS: SIGNIFICANCE FOR THERAPY

Developed by us conception of micropathogen associate acting like communicative organism was proposed. It allows predicting some pathogen responses to the presence of systemic localized lectins of probiotics. The rules of eukaryotic pathogen behavior in the presence of cascade probiotic lectins are formulated. New criteria of pathogenicity are described. The data will provide understanding the relationships of microbiota in biotopes as well as constructing directed space cascades of microbiocenose landscapes for medical biotechnology

DIVERSITY OF PROBIOTIC BACTERIAL LECTIN SYSTEMS

Lectin systems of industrial strains of probiotic bacteria of human origin were investigated. Lectin systems were observed as ceil surface and extracellular; solubilized in mild and firm conditions; solid phased fluorescent and chemiluminescent; anionic/acidic, neutral and cationic/alkaline; masked/biocked/encapsuiated with exopoiymeric substances of non-protein origin (localized together] and non-encapsuiated;genus/strain/consortia-specific and typing; specific to soluble artificial polymeric polyvalent glycoconjugates imitating exposed clusters of mucin-type glycans and possessing exposed multiple carbohydrate residues such asGalNAc-alpha- or Man-alpha- as side short branches of polyacrylamide linear chain). Results indicate prospects of glycoconjugates-binding lectin systems in glycobiology, molecularglyco- medicine and bio(nano)giycotechnoiogy

COFUNCTIONING OF PROTECTIVE SYSTEMS: MUCOSAL IMMUNITY AND HUMAN COMPLEMENT SYSTEM

Results on cofunctioning innate mucosal immunity (MI) and human complement system (HCS) pathways at steps of HCS initiation, amplification and termination were summarized. Receptor participants and pattern recognizing molecules (oligomeric lectins, multifunctional-site mucins and glycoproteins) of HCS and MI are taking into consideration. The ways of antipathogen cofunctioning MI and HCS are shown. The cases of viral, bacterial and fungal pathogens which use components, agent ingredients and reactions of HCS and Ml in pathogen strategies of invasion and survival in organism are represented. Prospects of cofunctioning MI and HCS, strategic directions of MI and HCS combinative using in development of medical aspects, constructing drugs and compositions of medical biotechnology significance are suggested and argued

Mucosal immunity to the pathogens and tumors involving system "lectins of probiotics - glycopolymers"

The overview of own works is devoted to the new insights to mucosal innate immunity functioning. We described multifunctional lectin systems of probiotic bacteria (LSPB) and their complexes which recognize a wide spectrum of selected glycoconjugates. LSPB (separately or in combinations with other antimicrobials and antipathogen factors) are important contributors to biotope distant protection against pathogens. Being metabolomebiotics, LSPB form reversible complexes to natural and artificial glycopolymers of mucin type that allows building on duty dynamic network of directed cascades of replies of mucosal innate immunity. Probiotic molecular-cellular network "LSPB - glycopolymers" serves as an important synergistic system participating in biotope microbiocenosis antipathogen resistance and in Cross-Talking communications with human protective cells and systems to support prolonged healthy status of mucosa. This network influences mucosa pores, affine texture, tropism and redistribution in biotope. Mucosal innate immunity strategies of LSPB and their complexes against microbial and viral pathogens, early tumor-like mucosal cells are proposed. Biological properties of artificial glycopolymers interacted in LS were compared

LECTINS IN ANTI-CANCER STRATEGIES

The published during last few years data concerning communicative role of lectins (proteins and their complexes which recognize  carbohydrates, glycoconjugates and their patterns) in on-duty  supporting and increasing anticancer status of human immunity are  analyzed. Examples of lectin-(glycoconjugate pattern) strategies,  approaches and tactic variants in study and development of  anticancer treatments, principle variants of therapy, possible  vaccines in 35 cases of blood connected tumors (leukemia,  lymphomas, others), solid tumors (carcinomas, sarcoma, cancers of vaginal biotopes, prostate, bladder, colon, other intestinal  compartments, pancreas, liver, kidneys, others) and cancer cell lines  are described and systemized. The list of mostly used communicative lectins (pattern recognition receptors, their soluble forms, other  soluble lectins possessing specificities of importance) involving in key intercellular cascades and pathway co-functioning is presented. The  regulation of resulting expression of distinct active lectins (available and hetero/di/oligomeric forms) and their interaction to  adequate glycoconjugate patterns as well as influence distribution of  co-functioning lectins and antigens CD between populations and  subpopulations of antigen-presented cells (dendritic cells cDC, mDC,  moDC, pDC; macrophages M2 and M1), mucosal M-cells, NK-cells  play key role for choice and development of anticancer complex  procedures increasing innate and innate-coupled immune responses.  Prospects of (receptor lectin)-dependent intercellular  communications and targeting glycoconjugate constructions into  innate immunity cells for therapy of cancer and development of anticancer vaccines are evaluated and discussed