@article {10747, title = {Activation of hepatic stem cells compartment during hepatocarcinogenesis in a HBsAg HBV-transgenic mouse model.}, journal = {Sci Rep}, volume = {8}, year = {2018}, month = {2018 Sep 03}, pages = {13168}, abstract = {

Chronic infection of Hepatitis B Virus (HBV) is one of the highest risk factors of hepatocellular carcinoma (HCC). The accumulation of HBV surface antigen (HBsAg) into hepatocytes induces inflammation and oxidative stress, impairing their replicative ability and allowing the activation of the hepatic stem cells (SC) compartment. This study aimed to understand the involvement of SC during hepatocarcinogenesis in HBsAg-related liver damage, from early injury until HCC. HBsAg-transgenic (TG) and wild type (WT) mouse were followed at several stages of the liver damage: inflammation, early hepatocytes damage, dysplasia, and HCC. Serum transaminases, liver histology, and diagnostic data were collected. The expressions of SC and cancer stem cells (CSC) markers was analyzed by RT-qPCR, immunohistochemistry and Western blot. Starting from 3 months, TG animals showed a progressive liver damage characterized by transaminases increase. The up-regulations of SCs markers Cd34 and Sca-1 started from the beginning of the inflammatory stage while progressive increase of Krt19 and Sox9 and CSCs markers Epcam and Cd133 from early hepatic injury. The expressions of Cd133, Cd34, and Afp were significantly higher in HCC compared to paired non-HCC tissue, in contrast to Epcam and Krt19. Western blot and IHC confirmed the positivity of Cd34 and Cd133 in small cells subpopulation.

}, issn = {2045-2322}, doi = {10.1038/s41598-018-31406-5}, author = {Anfuso, Beatrice and El-Khobar, Korri E and Ie, Susan I and Avellini, Claudio and Radillo, Oriano and Raseni, Alan and Tiribelli, Claudio and Sukowati, Caecilia H C} } @article {8499, title = {An Animal Model for the Juvenile Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis.}, journal = {PLoS One}, volume = {11}, year = {2016}, month = {2016}, pages = {e0158817}, abstract = {

Non Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) are the hepatic manifestations of the metabolic syndrome; worrisome is the booming increase in pediatric age. To recreate the full spectrum of juvenile liver pathology and investigate the gender impact, male and female C57Bl/6 mice were fed with high fat diet plus fructose in the drinking water (HFHC) immediately after weaning (equal to 3-years old human), and disease progression followed for 16 weeks, until adults (equal to 30-years old human). 100\% of subjects of both genders on HFHC diet developed steatosis in 4weeks, and some degree of fibrosis in 8weeks, with the 86\% of males and 15\% of females presenting a stage 2 fibrosis at 16weeks. Despite a similar final liver damage both groups, a sex difference in the pathology progression was observed. Alterations in glucose homeostasis, dyslipidemia, hepatomegaly and obese phenotype were evident from the very beginning in males with an increased hepatic inflammatory activity. Conversely, such alterations were present in females only at the end of the HFHC diet (with the exception of insulin resistance and the hepatic inflammatory state). Interestingly, only females showed an altered hepatic redox state. This juvenile model appears a good platform to unravel the underlying gender dependent mechanisms in the progression from NAFLD to NASH, and to characterize novel therapeutic approaches.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0158817}, author = {Marin, Veronica and Rosso, Natalia and Dal Ben, Matteo and Raseni, Alan and Boschelle, Manuela and Degrassi, Cristina and Nemeckova, Ivana and Nachtigal, Petr and Avellini, Claudio and Tiribelli, Claudio and Gazzin, Silvia} }