Partners:- The Donetsk national medical university Department of Histology, Cytology and Embryology

Department of Internal Medicine Department of Medical Biophysics, Medical Equipment and Clinical Informatics

- Rheumatologic Clinic

- Institute of Urgent and Recovery Surgery Laboratory of Fundamental Research

GENETIC FACTORSGENETIC FACTORS

Aggressive factors :

microbes (H. pylori), acid, bile, enzymes, nicotine,

alcohol, drugs

Aggressive factors :

microbes (H. pylori), acid, bile, enzymes, nicotine,

alcohol, drugs

INTEGRATING MECHANISMS (Neuro-Endocrine reactivity)INTEGRATING MECHANISMS (Neuro-Endocrine reactivity)

Tissues reactivity (GF, BAS, local regulators)Tissues reactivity (GF, BAS, local regulators)

CHRONIC INFLAMMATORY DISEASES

Immunological reactivityImmunological reactivity

Persistent inflammationPersistent inflammation

INJURYINJURY

CHRONIC INFLAMMATORY DISEASES

Unclear points:

-What genes and organospecific factors are involved?

- What are the common mechanisms of association between inflammatory diseases of joints and digestive system? - What cells and molecules should be the targets for therapeutic action of pharmaceutical agents?

NEURONEUROTRANSMITTERSTRANSMITTERS

NEURONEUROTRANSMITTERSTRANSMITTERS

LOCAL LOCAL REGULATIONREGULATION

LOCAL LOCAL REGULATIONREGULATION

IMMUNE STATEIMMUNE STATE BLOOD CELLSBLOOD CELLSIMMUNE STATEIMMUNE STATE BLOOD CELLSBLOOD CELLS

Proposition

CHRONIC INFLAMMATIONCHRONIC INFLAMMATIONTISSUES DESTRUCTIONTISSUES DESTRUCTION

CHRONIC INFLAMMATIONCHRONIC INFLAMMATIONTISSUES DESTRUCTIONTISSUES DESTRUCTION

NUTRIENTS. TOXINS, NUTRIENTS. TOXINS, DRUGSDRUGS

NUTRIENTS. TOXINS, NUTRIENTS. TOXINS, DRUGSDRUGS

Changes of stem cells kineticsChanges of stem cells kineticsViolation of reparationViolation of reparation

Changes of stem cells kineticsChanges of stem cells kineticsViolation of reparationViolation of reparation

PATIENTS WITH: - CHRONIC GASTRITIES; PEPTIC ULCERS (~200 patients), - CHRONIC PANCREATITIS (~200 patients), IRRITABLE BOWEL DISEASE (~200 patients)

PROPOSED STUDY DESIGN

MOLECULAR GENETIC ANALYSIS

- RHEUMATOID ARTHRITIS, SYSTEMIC LUPUS ERYTHEMATOSUS, POLYMYOSITIS, SYSTEMIC SCLEROSIS, ANKYLOSING SPONDYLITIS (~400 patients)

I . CLINICAL

I I . X-RAYS

I I I . DENSITOMETRY

I V. ATOMIC SPECTROMETRY

V. IMMUNOENZYME ANALYSIS

METHODS:

Approach for analysis

Investigation of the EXPRESSION PATTERN AND FUNCTION OF miRNAs

Investigation of INTERACTIONS

BETWEEN BLOOD CELLS

Leukocytes:- NADPH-oxidase- L-arginine metabolism- Cytokine production-Phagocytosis

Platelets-aggregation

INDUCTION BY:INDUCTION BY:-NeurotransmittersNeurotransmitters

-HormonesHormones-CytokinesCytokines

INHIBITION WITHINHIBITION WITH-receptor blockersreceptor blockers

- Inhibitors of Inhibitors of enzymes and enzymes and transductorstransductors

INDUCTION BY:INDUCTION BY:-NeurotransmittersNeurotransmitters

-HormonesHormones-CytokinesCytokines

INHIBITION WITHINHIBITION WITH-receptor blockersreceptor blockers

- Inhibitors of Inhibitors of enzymes and enzymes and transductorstransductors

EXPEXTED RESULTS

1. Key factors of reactivity which are associated with chronic inflammatory diseases

2. Informative criteria for early diagnostics and prognosis of chronic inflammatory diseases

3. Understanding of mechanisms of immune response regulation - for development of ways of immunomodulation.

4. Estimation of expression and role of miRNA in the MSCs will certify or revoke their therapeutic use for the control of autoimmunity.

THANK YOU FOR ATTANTION THANK YOU FOR ATTANTION