Serial changes in expression of functionally clustered genes in progression of liver fibrosis in hepatitis C patients

AIM: To investigate the relationship of changes in expression of marker genes in functional categories or molecular networks comprising one functional category or multiple categories in progression of hepatic fibrosis in hepatitis C (HCV) patients. METHODS: Marker genes were initially identified using DNA microarray data from a rat liver fibrosis model. The expression level of each fibrosis associated marker gene was analyzed using reverse transcription-polymerase chain reaction (RT-PCR) in clinical biopsy specimens from HCV-positive patients (n = 61). Analysis of changes in expression patterns and interactions of marker genes in functional categories was used to assess the biological mechanism of fibrosis. RESULTS: The profile data showed several biological changes associated with progression of hepatic fibrosis. Clustered genes in functional categories showed sequential changes in expression. Several sets of clustered genes, including those related to the extracellular matrix (ECM), inflammation, lipid metabolism, steroid metabolism, and some transcription factors important for hepatic biology showed expression changes in the immediate early phase (F1/F2) of fibrosis. Genes associated with aromatic amino acid (AA) metabolism, sulfur-containing AA metabolism and insulin/ Wnt signaling showed expression changes in the middle phase (F2/F3), and some genes related to glucose metabolism showed altered expression in the late phase of fibrosis (F3/F4). Therefore, molecular networks showing serial changes in gene expression are present in liver fibrosis progression in hepatitis C patients. CONCLUSION: Analysis of gene expression profiles from a perspective of functional categories or molecular networks provides an understanding of disease and suggests new diagnostic methods. Selected marker genes have potential utility for biological identification of advanced fibrosis.

Gene expression profiles of hepatic cell-type specific marker genes in progression of liver fibrosis

AIM: To determine the gene expression profile data for the whole liver during development of dimethylni-trosamine (DMN)-induced hepatic fibrosis.METHODS: Marker genes were identified for different types of hepatic cells, including hepatic stellate cells (HSCs), Kupffer cells (including other inflammatory cells), and hepatocytes, using independent temporal DNA microarray data obtained from isolated hepatic cells. RESULTS: The cell-type analysis of gene expression gave several key results and led to formation of three hypotheses: (1) changes in the expression of HSC-specific marker genes during fibrosis were similar to gene expression data in in vitro cultured HSCs, suggesting a major role of the self-activating characteristics of HSCs in formation of fibrosis; (2) expression of mast cell-specific marker genes reached a peak during liver fibrosis, suggesting a possible role of mast cells in formation of fibrosis; and (3) abnormal expression of hepatocyte-specific marker genes was found across several metabolic pathways during fibrosis, including sulfur-containing amino acid metabolism, fatty acid metabolism, and drug metabolism, suggesting a mechanistic relationship between these abnormalities and symptoms of liver fibrosis. CONCLUSION: Analysis of marker genes for specific hepatic cell types can identify the key aspects of fibro-genesis. Sequential activation of inflammatory cells and the self-supporting properties of HSCs play an important role in development of fibrosis.

Feral Cats: Parasitic Reservoirs in Our Zoos?

Up until the recent past, zoos served limited function, primarily existing for entertainment value. Today’s zoos, however, are serving many roles, chief among them: species conservation of captive animals. The biggest zoo in Brazil, S?o Paulo Zoological Park Foundation, has among its 2000 animals and many species of wild cats. The presence of domestic cats living freely in zoos is common and can be a source of spreading disease. The aim of this study was to verify the variety and prevalence of parasites found in the feces of felids (feral and wild) living in the S?o Paulo Zoo. The results of this parasitological analysis have been obtained from the laboratory of clinical analysis and correspond to the 4-year period beginning January/2009 and ending December/2012. Eight species of parasites were identified in the feces of captive wild cats and three in the feces of feral cats. For those captives, Toxocara cati (7.95%) had the highest prevalence, followed by Toxascaris leonina (7.58%), Isospora sp. (2.03%), Hymenolepis nana (0.92%), Eimeria sp., Giardia sp. and Blastocystis sp. (0.37% each) and Ascaris sp. (0.18%). Among the feral cats, we found Toxocara cati (59.26%), Giardia sp. (22.22%) and Isospora sp. (11.11%). For the captive group, we also distinguished natives from exotic species, finding native species to be more frequently parasitized than the exotic ones. Key to our findings, though, was the fact that a few parasite species were found among all groups of felids, specifically (Toxocara cati, Giardia sp. and Isospora sp). Further research is needed, however, to confirm that transmission of these parasites is occurring between and among these groups.