[Clinical and metabolic features of nonalcoholic fatty liver disease in men and women]. / Klinicheskie i metabolicheskie osobennosti nealkogol'noi zhirovoi bolezni pecheni u muzhchin i zhenshchin.

AIM: To evaluate clinical features and metabolic disorders in men and women with non-alcoholic fatty liver disease (NAFLD).

NON-ALCOHOLIC FATTY LIVER DISEASE IN ELDERLY.

AIM: The study of the clinical course and metabolic disorders in patients nonalcoholic fatty liver disease (NAFLD) elderly. SUBJECTS AND METHODS: 153 patients with NAFLD was investigated, including 97 men and 56 women. In comparative terms we studied clinical manifestations of NAFLD. All patients NAFLD was verified for the first time. We studied the functional state of the liver function, lipid, carbohydrate and porphyrin metabolism, insulin resistance. RESULTS: Revealed comorbid pathology, which is predominantly observed in elderly patients. Disturbances in lipid metabolism and insulin resistance hyperinsulinemiya and proved to be more significant in young patients. Disorders of porphyrin metabolism observed in most patients. Disorders are variable. Do young people have dominated the initial disorder, on the other hand more often in elderly patients were observed faction (later) porphyrin metabolism disorders. CONCLUSION: Studies suggest that the main pathophysiologic and pathogenetic processes of formation of NAFLD (insulin resistance and dyslipidemia) significantly more pronounced in younger patients. This fact suggests that NAFLD is mainly formed at a young age. Elderly patients have comorbid pathology.

[ALLELES C282Y AND H63D HFE GENE, INSULIN RESISTANCE AND SUSCEPTIBILITY TO DISTURBANCE OF PORPHYRIN METABOLISM IN NON-ALCOHOLIC FATTY LIVER DISEASE].

THE PURPOSE OF THE STUDY: The aim of the present work was to study the frequency of genotypes and alleles of C282Y and H63D HFE gene that may be associated with impaired porphyrin metabolism, as well as possible reasons for the formation of dysmetabolism porphyrins with NAFLD. MATERIALS AND METHODS: The study involved 65 patients (52 men and 13 women) aged 21 to 69 years (mean age 48.5±1.5 years). Excretion uroporphyrin, coproporphyrin, 6-aminolevulinic acid of porphobilinogen in urine was determined by chromatography and spectrophotometry calculated total excretion of porphyrins. Allele frequencies C282Y and H63D were determined during the molecular genetic analysis of DNA using the polymerase chain reaction followed by analysis of length polymorphism restraktsionnyh fragments. Condition of carbohydrate metabolism was evaluated by the level of fasting blood glucose and standard glucose tolerance test. Diagnosis of insulin resistance was performed according to the criteria proposed by the European Group for the Study of insulin resistance (EGIR). RESULTS: Skill test for the C282Y mutation carriage and H63D in the HFE gene in 65 patients with non-alcoholic fatty liver disease. Disturbances in the metabolism of porphyrins were recorded in 43 (66.2%) patients. H63D and C282Y mutations were found in 18 (27.7%) patients, of whom 13 (72.2%) people with different options dismetabolism porphyrins and signs of insulin resistance. In 47 (72.3%) patients without mutations studied porphyrin metabolism disorders were detected in 30 (63.8 %), of which insulin resistance is registered only in 16 (34.0 %). CONCLUSION: Detection of mutations C282Y and H63D in the HFE gene in combination with disorders of porphyrin metabolism on the background of insulin resistance is likely to allow such patients considered as candidates for inclusion in the higher risk of formation of diabetes.

Atlas of Cancer Signalling Network: a systems biology resource for integrative analysis of cancer data with Google Maps.

Cancerogenesis is driven by mutations leading to aberrant functioning of a complex network of molecular interactions and simultaneously affecting multiple cellular functions. Therefore, the successful application of bioinformatics and systems biology methods for analysis of high-throughput data in cancer research heavily depends on availability of global and detailed reconstructions of signalling networks amenable for computational analysis. We present here the Atlas of Cancer Signalling Network (ACSN), an interactive and comprehensive map of molecular mechanisms implicated in cancer. The resource includes tools for map navigation, visualization and analysis of molecular data in the context of signalling network maps. Constructing and updating ACSN involves careful manual curation of molecular biology literature and participation of experts in the corresponding fields. The cancer-oriented content of ACSN is completely original and covers major mechanisms involved in cancer progression, including DNA repair, cell survival, apoptosis, cell cycle, EMT and cell motility. Cell signalling mechanisms are depicted in detail, together creating a seamless 'geographic-like' map of molecular interactions frequently deregulated in cancer. The map is browsable using NaviCell web interface using the Google Maps engine and semantic zooming principle. The associated web-blog provides a forum for commenting and curating the ACSN content. ACSN allows uploading heterogeneous omics data from users on top of the maps for visualization and performing functional analyses. We suggest several scenarios for ACSN application in cancer research, particularly for visualizing high-throughput data, starting from small interfering RNA-based screening results or mutation frequencies to innovative ways of exploring transcriptomes and phosphoproteomes. Integration and analysis of these data in the context of ACSN may help interpret their biological significance and formulate mechanistic hypotheses. ACSN may also support patient stratification, prediction of treatment response and resistance to cancer drugs, as well as design of novel treatment strategies.

[Porphyrin metabolism in women with metabolic syndrome].

A total of 47 women with metabolic syndrome (MS) were examined with the fractional determination of porphyrins in urine (uroporphyrin and coproporphyrin) and feces (coproporphyrin and protoporphyrin) as well as their precursors (5-aminolevulinic acid and porphobilinogen). Disorders of porphyrin metabolism were documented in 29 (61.7%) women All patients had elevated levels of porphyrin precursors. Five women exhibited qualitative changes in the form of abnormal ratios of different porphyrin fractions(coproporphyrin/uroporphyrin < 1--0.8 ± 0.1 vs normal ratio 3.6 ± 0.4). 21 patients suffered quantitative changes in porphyrin metabolism in the form of manifold increase of porphyrin levels in urine and/or feces and formation of biochemical syndromes of secondary coproporphyrinuiria, symptomatic rise in porphyrin content in feces, and chronic latent hepatic porfiria. Disorders of porphyrin metabolism were associated with insulin resistance. Changes of porphyrin metabolism in MS extend the spectrum of concomitant disturbances and can be regarded as an additional criterion.

[The porphyrin metabolism in liver cirrhosis].

AIM: To comparatively study porphyrin metabolic disturbances in liver cirrhosis (LC) of varying etiology and to estimate the diagnostic and prognostic value of the detected disorders. SUBJECTS AND METHODS: Seventy-one patients were examined; among them 34, 15, and 22 patients were diagnosed as having alcoholic, viral, and alcoholic-and-viral LC, respectively. Its predictors and porphyrin fractions were determined in their urine and feces. RESULTS: Porphyrin metabolic disturbances were recorded in 62 (87.3%) patients and found in the majority of patients with viral (86.7%), alcoholic (94.1%), and mixed (77.3%) LC. The detected abnormalities corresponded to 4 variants of porphyrin dysmetabolism: elevation of porphyrin predictors, biochemical syndromes of symptomatic elevation of fecal porphyrins, secondary coproporphyrinuria, and latent chronic hepatic porphyria (LCHP). Some patients were found to have comorbidities, suggesting the stepwise development of porphyrin dysmetabolism. The disturbances were identified in patients with LC irrespective of the Child-Pugh class. The prognostically less favorable biochemical syndrome LCHP was recorded only in the presence of progressive hepatocellular failure in Child's class C decompensated LC. This trend should be considered to be prognostically unfavorable, preceding or occurring in the presence of decompensated LC that is more often a cause of death in this contingent of patients. CONCLUSION: Porphyrin metabolism should be regarded as a highly sensitive indicator. The differential assessment of the porphyrin excretory profile may be referred to as additional diagnostic and prognostic criteria indicating the Child-Pugh class.

[Comparative characteristics of porphyrins metabolism in chronic viral diseases of the liver].

AIM: To study porphirin metabolism in chronic viral infections of the liver. MATERIAL AND METHODS: The examination of 101 patients with hepatic viral infections diagnosed chronic HCV-infection in 30 patients, chronic HBV infection in 25 patients and combined infection in 6patients. Patients with chronic alcohol intoxication were not included in the trial. Urinary uroporphirin and coproporphirin (CP), fecal protoporphirin and CP were estimated. Total porphirines were calculated. RESULTS: 29 patients with chronic viral hepatitis had no porphirin disbolism. The latter (elevation of porphirine fractions in the urine and/or feces) was detected in 11 (84.6%) of 13 patients with hepatic cirrhosis (HC). Biochemical syndromes of elevated fecal porphirines, secondary coproporphirinuria, chronic latent hepatic porphiria were developing. The above disorders progressed with aggravation of the disease severity. In manifest late skin porphiria chronic HCV infection was detected in 19 (32.2%) of 59 patients. CONCLUSION: In non-alcoholic patients with chronic diffuse diseases of the liver of viral etiology nonspecific disturbances of porphirine metabolism develop at the stage of arising HC and are registered more frequently in the presence of chronic HBV-infection. Frequent combination of chronic HCV-infection with manifest late skin porphiria suggests a trigger role of HCV initiating specific disbolism of porphirines in this disease.

[Novel structural tree for beta-proteins containing abcd-units].

A database of 528 beta-proteins and beta-domains containing abcd-units (among them 244 are nonhomologous) has been compiled from the Protein Data Bank (total 1511 PDB entries). A novel structural tree for this structural class of proteins that is composed of 153 possible polypeptide chain folds has been constructed. The structural classification of beta-proteins containing abcd-unit based on the structural tree has been developed. Both the database and the structural tree are accessible at the web-site (http://strees.protres.ru/).

Structural features of protein folding nuclei.

A crucial event of protein folding is the formation of a folding nucleus. We demonstrate the presence of a considerable coincidence between the location of folding nuclei and the location of so-called "root structural motifs", which have unique overall folds and handedness. In the case of proteins with a single root structural motif, the involvement in the formation of a folding nucleus is in average significantly higher for amino acids residues that are in root structural motifs, compared to residues in other parts of the protein. The tests carried out revealed that the observed difference is statistically reliable. Thus, a structural feature that corresponds to the protein folding nucleus is now found.

[A comparative analysis of interhelical polar interactions of various alpha-helix packings in proteins]. / Sravnitel'nyi analiz mezhspiral'nykh poliarnykh vzaimodeistvii v razlichnykh upakovkakh alpha-spiralei v belkakh.

One hundred twenty globular proteins and forty five "leucine zippers" representing all types of packing of long alpha-helices were studied in terms of revealing and comparing their interhelical hydrogen and salt bonds. Many previous studies of "leucine zippers" and their analogs showed that interhelical interactions between polar groups could impart specificity to packing of an alpha-helix. The current comparison demonstrated that basically, globular proteins and "leucine zippers" had similar interhelical polar interactions with presumably a similar structural role. However, depending on packing of alpha-helices, the networks of interhelical polar bonds were shown to be distinct and determined both by physicochemical properties of involved amino acid residues and by the relative positions of hydrophobic and hydrophilic residues on the surface of alpha-helices. The revealed distinction is probably crucial for selecting the unique packing of an alpha-helix.

[Systematic analysis of buried polar side chains and their interactions in alpha-helical proteins]. / Sistematicheskii analiz spriatannykh poliarnykh bokovykh tsepei i ikh vzaimodeistvii v alpha-spiral'nykh belkakh.

Examination of 80 alpha-helical proteins and domains demonstrates that they contain from 1 to more than 20 completely buried (water-inaccessible) polar side chains. As a rule the latter have partners for H-bonding but the resulting H-bond system is often not exhaustive. Basing on statistical analysis, we determined the optimal number of H-bonds for every type of polar side chain, and discuss the structural role of vacant donors and acceptors. About half of the H-bonds formed by buried side chains pertain to interhelix contacts of the (side chain)-(side chain) and (side chain)-(main chain) types. Such interactions appear to be a most important factor determining the mutual arrangement of alpha-helices in proteins. Analysis of the frequency of occurrence of various interacting pairs reveals that these interactions are selective.