Role of MMP-2 and MMP-9 in the Relationship between Inflammation, Fibrosis, and Apoptosis during Progression of Non-Alcoholic Fatty Liver Disease and Diagnostic Significance of Plasma Levels of Their Active Forms.

MMP-2 and MMP-9 play an important role in pathogenesis of chronic liver diseases, participating in the processes of inflammation and fibrosis. Their role in progression of non-alcoholic fatty liver disease (NAFLD) is poorly understood. Analysis of MMP-2, -9 levels in the blood plasma of patients with different forms of NAFLD [liver steatosis (LS) and non-alcoholic steatohepatitis (NASH) of weak (-WA), moderate (MA), high (-HA) activity without pronounced fibrosis] was performed.

Blood Level of Nitric Oxide Metabolites and Expression of Genes Regulating NO Synthesis in Early Forms of Non-Alcoholic Fatty Liver Disease.

The levels of NO metabolites in the plasma and mRNA of the NOS3, ATG9B, and NOS2 genes in peripheral blood leukocytes of healthy people and patients with early forms of non-alcoholic fatty liver disease (steatosis and weak activity non-alcoholic steatohepatitis) were studied. In patients with steatohepatitis, the concentration of NO metabolites in the blood and the level of mRNA of the NOS2 gene were higher than in patients with steatosis and healthy people. These differences can be of diagnostic value for distinguishing between steatosis and weak activity steatohepatitis in non-alcoholic fatty liver disease.

The Role of the Soluble Interleukin-6 Receptor in the Progression of Nonalcoholic Fatty Liver Disease.

The blood level of soluble IL-6 receptor was measured in patients with different clinical and morphological forms of nonalcoholic fatty liver disease and healthy donors. The relationship of the soluble IL-6 receptor with the content of IL-6, the level of the IL6 gene mRNA, and a number of markers of hepatocyte and peripheral blood leukocyte apoptosis was assessed. It has been established for the first time that progression of nonalcoholic fatty liver disease is associated with changes in the level of soluble IL-6 receptor in the blood.

Hepatocytic Apoptosis and Immune Dysfunction in Decompensation of Alcoholic Liver Cirrhosis with Different Grades of Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) of varying grades was assessed in 110 patients with alcoholic liver cirrhosis using the on-line CLIF-C ACLF Calculator ( www.efclif.com/scientific-activity/score-calculators/clif-c-aclf ); fragments of cytokeratin-18, TNFα, IL-1β, IL-4, IL-6, and IL-8 were also assayed.

Role of Bacterial Infection in the Development of Acute Liver Failure in Patients with Decompensated Alcoholic Liver Cirrhosis.

We examined 74 patients with acute decompensation of alcoholic liver cirrhosis: 34 (45.9%) with bacterial infection (group 1) and 40 (54.1%) without bacterial infection (group 2).

[Hepatocellular damage and inflammation in various forms of alcoholic liver disease].

Aim: The aim of the study was to evaluate hepatocellular damage and immune inflammation in various forms of alcoholic liver disease (ALD).

Materials And Methods: 104 patients with ALD were examined: 15 (14.4%) with liver steatosis (LS), 19 (18.

The relationship of the carriership of allelic variations in rs2228145 (A > C) of the IL6R gene with the levels of VCAM1 and ICAM1 gene transcripts in patients with essential hypertension.

The levels of plasma interleukin 6 and its soluble receptors were found to be elevated in subjects with cardiovascular diseases, which points to amplification of the IL-6-mediated trans-signaling pathway in cells and the development of chronic inflammation. The allelic variation in the rs2228145 IL6R gene is associated with a change in the contents of the soluble and membrane-bound receptor forms mediating the biological activity of IL-6. Cytokine IL-6 is involved in the development of endothelial dysfunction by regulating the expression of the VCAM1 and ICAM1 genes, encoding intercellular adhesion molecules.

Biochemical and molecular-genetic indicators of inflammation and apoptosis in liver cirrhosis as an outcome of the progression of non-alcoholic steatohepatitis.

Aim: A comparative analysis of the complex of clinical and laboratory indicators (including the content of cytokines in blood plasma and the level of expression of TNF and IL6 genes in peripheral leukocytes, as well as the level of biochemical and molecular-genetic indicators of apoptosis, such as the content of tissue polypeptide-specific antigen (TPS) in the blood, the activity of caspases 3, 8 and 9 and the expression level of the encoding genes in peripheral blood leukocytes) in patients with non-alcoholic fatty liver disease (NAFLD) with non-alcoholic steatohepatitis (NASH) of different activity, liver cirrhosis (LC) classes A and B and in the donors of control group.

Materials And Methods: 158 patients with NAFLD were examined: 116 patients with NASH diagnosed for the first time (NASH of weak, moderate and high activity) and 42 patients with the NAFLD at the stage of liver cirrhosis diagnosed for the first time (classes A and B according to the Child-Pugh classification). The control group consisted of 54 healthy donors.

The clinical significance of insulin resistance in non-diabetic patients with early forms of non-alcoholic fatty liver disease.

Aim: To assess the presence of insulin resistance (IR) in non-diabetic patients with early forms of non-alcoholic fatty liver disease (NAFLD) - liver steatosis (LS) and steatohepatitis (SH) of mild activity and the influence of IR on the clinical course of these diseases.

Materials And Methods: 134 patients with NAFLD were examined: 54 with LS and 80 with SH. The control group consisted of 37 healthy donors.

Analysis of the Association of TNF -238G>A Gene Polymorphism with the Risk of Rheumatoid Arthritis Development in Russian Population in the Republic of Karelia.

We studied association of the TNF gene -238G>A polymorphism (rs361525) with the risk of rheumatoid arthritis development in the Russian population living in the Republic of Karelia. The influence of rs361525 on the development of rheumatoid arthritis was revealed: genetic predisposition to this disease is associated with the presence of GG genotype. The effect of the genotype on the polymorphic locus of -238G>A on TNF mRNA content was revealed.

IL6R Gene Polymorphic Variant rs2228145(C >A) as a Marker of Genetic Liability to Nonalcoholic Steatohepatitis in the Russian Population of Karelia.

Association of IL6R gene polymorphic variant rs2228145(C>A) with the development of nonalcoholic steatohepatitis in Karelia residents is detected. The risk of nonalcoholic steatohepatitis is more than 2-fold higher in carriers of CC genotype by rs2228145 polymorphic marker than in carriers of other genotypes. Plasma levels of IL-6 and the content of IL6R gene transcripts in the peripheral blood leukocytes are higher in patients with nonalcoholic steatohepatitis than in normal subjects.

[Association of FOXP3 gene -3279 C>A polymorphism with the risk of pulmonary sarcoidosis].

Aim: To investigate the association of the polymorphic marker -3279 C>A of the FOXP3 gene with the risk of pulmonary sarcoidosis (PS) and to estimate the transcription level of this gene in the carriers of different genotypes of this polymorphic marker.

Subjects And Methods: The investigation included 99 patients of Russian ethnicity (mean age, 45.41±1.

Gene TNF Polymorphism -308G>A (rs1800629) and Its Relationship with the Efficiency of Ursodeoxycholic Acid Therapy in Patients with Nonalcoholic Stetohepatitis.

Association of TNF gene polymorphism -308G>A with the development of nonalcoholic steatohepatitis in the Russian population was revealed. Carriers of allele A of the TNF gene marker -308G>A have significantly higher risk of nonalcoholic steatohepatitis development: OR=1.69 (1.

[Circadian CLOCK Gene Variants, Parameters of Arterial Stiffness and Blood Pressure Levels in Subjects Without Arterial Hypertension].

CLOCK gene polymorphic variants, parameters of arterial stiffness and blood pressure (BP) variability were studied in 115 normotensive Russian patients without cardiovascular diseases (62 men, 53 women; mean age 36.4+/-1.01 years).

[Features of a necrotic and inflammatory process in different forms of nonalcoholic fatty liver disease].

Aim: To identify the features of development of a necrotic and inflammatory process in different forms of nonalcoholic fatty liver disease (NAFLD), by comparatively analyzing a full set of clinical and laboratory parameters, including the cytokine status and the expression level of enzyme genes controlling the apoptosis of peripheral leukocytes.

Subjects And Methods: 86 patients with NAFLD, including 8 (9.3%) with hepatic steatosis (HS), 70 (81.

Caspase 3, 6, 8, and 9 Gene Expression in Peripheral Blood Leukocytes and Plasma Concentrations of IL-6 and TNF-α in Carriers of Different Polymorphic Marker -174G>C Genotypes of IL6 Gene Associated with the Risk of Nonalcoholic Steatohepatitis.

We revealed an association of IL6 gene -174G>C polymorphism with the development of nonalcoholic steatohepatitis in the Russian population. The risk is significantly higher in carriers of C allele: OR=1.77 (1.

The level of cytokines and expression of caspase genes in rheumatoid arthritis.

The level of TNFα and IL6 in the blood plasma of patients with rheumatoid arthritis (RA) who received antiinflammatory therapy with methotrexate (MT) was significantly lower than in the patients without MT treatment. The level of caspase 6 and 9 gene transcripts in peripheral blood lymphocytes in patients with rheumatoid arthritic diagnosed for the first time and in patients with MT treatment were not significantly different. At the same time, the level of caspase 3 mRNA expression was significantly higher in the cells of the RA patients with MT therapy compared to the patients without MT therapy.

[EFFICIENCY OF URSODEOXYCHOLIC ACID APPLICATION IN NONALCOCHOLIC STEATOHEPATITIS].

Aim: to estimate the efficiency of ursodeoxycholic acid (UDHC) in nonalcocholic steatohepatitis (NASH) by analysis of conventional clinical datas, apoptosis and liver perfusion parameters.

Materials And Methods: UDHC was used as monotherapy in treatment of 92 NASH patients in daily dose 10-15 mg/kg. We have observed 44 (47.

[Energy and mass exchange and the productivity of the main ecosystems of Siberia (from eddy covariance measurements). 1. Heat balance structure in the vegetation season].

Direct measurements of heat balance (turbulent heat transfer and evaporation heat consumption) by the method of turbulent pulsations in 1998-2000 and 2002-2004 were used to obtain information on the daily, seasonal, and annual dynamics of energy fluxes and mass transfer between the atmosphere and the typical ecosystems of Siberia (middle-taiga pine forest and raised bog, true four-grass steppe, with the use of data for typical tundra) along the Yenisei meridian (90 degrees E).

Expression of circadian rhythm genes CLOCK, BMAL1, and PER1 in buccal epithelial cells of patients with essential arterial hypertension in dependence on polymorphic variants of CLOCK and BMAL1 genes.

The transcript levels of circadian rhythm genes CLOCK, BMAL1, and PER1 in buccal epithelial cells of the patients with essential arterial hypertension was analyzed in relation to polymorphic variants of CLOCK and BMAL1 genes. These levels were assessed with realtime PCR method at daily hours 9, 13, and 17. The significant differences were revealed in transcript levels of the examined genes in patients with various genotypes at the polymorphic markers 3111TC and 257TG regulatory regions of CLOCK gene.

Toll-like receptor-mediated down-regulation of the deubiquitinase cylindromatosis (CYLD) protects macrophages from necroptosis in wild-derived mice.

Pathogen recognition by the innate immune system initiates the production of proinflammatory cytokines but can also lead to programmed host cell death. Necroptosis, a caspase-independent cell death pathway, can contribute to the host defense against pathogens or cause damage to host tissues. Receptor-interacting protein (RIP1) is a serine/threonine kinase that integrates inflammatory and necroptotic responses.

[Energy and mass transfer and the productivity of the main ecosystems of Siberia (according to the results of measurements by the method of turbulent pulsations). 2. Carbon exchange and productivity].

Using direct measurements of CO2 fluxes by the method of turbulent pulsations, it was shown that the studied middle-taiga pine forest, raised bog, true steppe, and southern tundra along the Yenisei meridian (approximately 90 degrees E) are stocks of carbon of different capacity in the annual output. The tundra starts to function as a stock of carbon from June; the forest and bog, from May; and the steppe, from the end of April. In the transitional seasons and winter, the ecosystems are a weak source of carbon: the tundra already in September; the forest and bog, from October; and the steppe, from November.

[Tourism, imported parasitic diseases, and their prevention].

The paper gives the results of observations of 1558 patients before and after tourist travels to tropical countries and 368 individuals visiting the north areas of the Russian Federation. Different conditions (malaria, amebiasis, leishmaniasis, intestinal and tissue helminthiasis, insect bites, venomous fish pricks, medusa burn, tick bites, etc.) were found in 402 persons.

[The possibility of antibiotic therapy in leishmaniasis].

The authors describe cases of leishmaniasis for which claforan (cefotaxime) has been used, showing an obvious improvement in visceral leishmaniasis in children and a full recovery in cutaneous leishmaniasis in adults.