A5034481559- Liver Disease Diagnosis and Treatment
- Liver physiology and pathology
- Pediatric Hepatobiliary Diseases and Treatments
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Liver Diseases and Immunity
- Pancreatic function and diabetes
- Organ Transplantation Techniques and Outcomes
- Liver Disease and Transplantation
- Pancreatic and Hepatic Oncology Research
- Tissue Engineering and Regenerative Medicine
- Pancreatitis Pathology and Treatment
- Diet, Metabolism, and Disease
- Diet and metabolism studies
- Peptidase Inhibition and Analysis
- Gallbladder and Bile Duct Disorders
- MicroRNA in disease regulation
- Bone and Dental Protein Studies
- Endoplasmic Reticulum Stress and Disease
- 3D Printing in Biomedical Research
- Diabetes and associated disorders
- Diabetes Management and Research
- Hedgehog Signaling Pathway Studies
- Pluripotent Stem Cells Research
- Lipid metabolism and disorders
- Drug Transport and Resistance Mechanisms
Sapienza University of Rome
2015-2024
Azienda Ospedaliera G.Rummo
2015
Background and Aims Lipopolysaccharides (LPS) is increased in nonalcoholic fatty liver disease (NAFLD), but its relationship with inflammation not defined. Approach Results We studied Escherichia coli LPS patients biopsy‐proven NAFLD, 25 simple steatosis (nonalcoholic liver) steatohepatitis (NASH), mice diet‐induced NASH. NASH had higher serum hepatocytes localization than controls, which was correlated zonulin phosphorylated nuclear factor‐κB expression. Toll‐like receptor 4 positive (TLR4...
Background There are no licensed treatments for non alcoholic fatty liver disease (NAFLD) in adults or children. In NAFLD, several studies have shown a benefit of omega-3 acid treatment on lipid profile, insulin-sensitivity and hepatic steatosis it has also been suggested that Vitamin D potential antifibrotic properties disease. Trial Design To date, however, there tested the combination Docosahexanoic (DHA) vitamin which may whole spectrum NAFLD. Our aim therefore, was to test effect daily...
Peribiliary glands (PBG) are a source of stem/progenitor cells organized in cellular network encircling large bile ducts. Severe cholangiopathy with loss luminal biliary epithelium has been proposed to activate PBG, resulting cell proliferation and differentiation restore epithelial integrity. However, formal evidence for this concept human livers is lacking. We therefore developed an ex vivo model using precision‐cut slices extrahepatic ducts obtained from discarded donor livers, providing...
Abstract Pathogenesis of non-alcoholic fatty liver disease (NAFLD) is influenced by predisposing genetic variations, dysmetabolism, systemic oxidative stress, and local cellular molecular cross-talks. Patatin-like phospholipase domain containing 3 (PNPLA3) gene I148M variant a known determinant NAFLD. Aims were to evaluate whether PNPLA3 was associated with specific histological pattern, hepatic stem/progenitor cell (HpSC) niche activation serum stress markers. Liver biopsies obtained from...
Primary sclerosing cholangitis (PSC) is a chronic inflammatory cholangiopathy frequently complicated by cholangiocarcinoma (CCA). Massive proliferation of biliary tree stem/progenitor cells (BTSCs), expansion peribiliary glands (PBGs), and dysplasia were observed in PSC. The aims the present study to evaluate involvement PBGs BTSCs CCA which emerged PSC patients. Specimens from normal liver (n = 5), 20), PSC‐associated 20) included. Samples processed for histology, immunohistochemistry,...
Cholangiocarcinoma (CCA) is an aggressive cancer with high resistance to chemotherapeutics. CCA enriched in stem cells, which correlate aggressiveness and prognosis. FXR, a member of the metabolic nuclear receptor family, markedly down-regulated human CCA. Our aim was evaluate, primary cultures intrahepatic (iCCA), effects FXR agonist obeticholic acid (OCA), semisynthetic bile derivative, on their cancerogenic potential. Primary iCCA cell were prepared from surgical specimens mucinous or...
Mechanisms underlying the repair of extrahepatic biliary tree (EHBT) after injury have been scarcely explored. The aims this study were to evaluate, by using a lineage tracing approach, contribution peribiliary gland (PBG) niche in regeneration EHBT damage and vivo vitro, signaling pathways involved.Bile duct was induced administration 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet for 14 days Krt19Cre TdTomatoLSL mice. Human stem/progenitor cells (BTSC) within PBGs isolated from...
Background and Aims Liver fibrosis holds a relevant prognostic meaning in primary biliary cholangitis (PBC). Noninvasive evaluation using vibration‐controlled transient elastography (VCTE) is routinely performed. However, there limited evidence on its accuracy at diagnosis PBC. We aimed to estimate the diagnostic of VCTE assessing advanced (AF) disease presentation Approach Results collected data from 167 consecutive treatment‐naïve PBC patients who underwent liver biopsy (LB) six Italian...
Gut-dysbiosis-induced lipopolysaccharides (LPS) translocation into systemic circulation has been suggested to be implicated in nonalcoholic fatty liver disease (NAFLD) pathogenesis. This study aimed assess if oleuropein (OLE), a component of extra virgin olive oil, lowers high-fat-diet (HFD)-induced endotoxemia and, eventually, steatosis. An immunohistochemistry analysis the intestine and was performed (i) control mice (CTR; n = 15), (ii) fed (HFD) (HFD; 16), (iii) HFD treated with 6 µg/day...
Abstract Pancreatic duct glands ( PDG s) are tubule‐alveolar associated with the pancreatic system and can be considered anatomical counterpart of peribiliary PBG found within biliary tree. Recently, we demonstrated that endodermal precursor niches exist fetally postnatally composed functionally stem cells progenitors s committed s. Here have characterized more extensively anatomy human as novel containing multiple phenotypes progenitors. Human pancreata n = 15) were obtained from cadaveric...
Intrahepatic cholangiocarcinoma (iCCA) is a malignancy that arises from the intrahepatic biliary tree, showing high mortality rates due to its late clinical presentation and limited treatment options. iCCA characterized by dense, reactive desmoplastic stroma marked dramatic accumulation of extracellular matrix (ECM). Although recent results strongly suggest relationship between increasing enhanced malignant behaviour iCCA, importance ECM proteins in pathogenesis still have be addressed.iCCA...
Cholangiocarcinoma (CCA) is a very aggressive cancer showing the presence of high stem cells (CSCs). Doublecortin-like kinase1 (DCLK1) has been demonstrated as CSC marker in different gastroenterological solid tumors. Our aim was to evaluate vitro expression and biological function DCLK1 intrahepatic CCA (iCCA) perihilar (pCCA).Specimens surgically resected human were enzymatically digested, submitted immunosorting for specific markers (LGR5 [leucine-rich repeat-containing G protein-coupled...
Abstract Many pivotal biological cell processes are affected by gravity. The aim of our study was to evaluate and functional effects, differentiation potential exo-metabolome profile simulated microgravity (SMG) on human hepatic line (HepG2) biliary tree stem/progenitor cells (hBTSCs). Both hBTSCs HepG2 were cultured in a weightless protected environment SGM produced the Rotary Cell Culture System (Synthecon) control condition normal gravity (NG). Self-replication toward mature determined...
Objective Cytotoxic agents are the cornerstone of treatment for patients with advanced intrahepatic cholangiocarcinoma (iCCA), despite heterogeneous benefit. We hypothesised that pretreatment molecular profiles diagnostic biopsies can predict patient benefit from chemotherapy and define bases innate chemoresistance. Design identified a cohort iCCA comparable baseline characteristics who diverged as extreme outliers on (survival <6 m in rapid progressors, RP; survival >23 long...
The term cholangiocarcinoma (CCA) defines a class of epithelial malignancies originating from bile ducts. Although it has been demonstrated that CCA patients with perineural invasion (PNI) have worse prognosis, the biological features this phenomenon are yet unclear. Our data show in human intrahepatic specimens documented PNI, nerve-infiltrating cells display positivity marker cytokeratin 7, lower respect to rest tumor mass. In an vitro 3D model, move towards peripheral nerve explant...
Abstract Intrahepatic cholangiocarcinoma (iCCA) represents a heterogeneous group of malignancies emerging from the biliary tree, often in context chronic bile ducts inflammation. The immunological features iCCA cells and their capability to control lymphocytes response have not yet been investigated. aims present study were evaluate interaction between human peripheral blood mononuclear (PBMCs) role Fas/FasL modulating T-cells NK-cells after direct co-culture. express high levels Fas FasL...
Abstract Background and Aims Nonanastomotic biliary strictures (NAS) are a major cause of morbidity after orthotopic liver transplantation (OLT). Although ischemic injury peribiliary glands (PBGs) vascular plexus during OLT has been associated with the later development NAS, exact underlying mechanisms remain unclear. We hypothesized that bile ducts patients NAS suffer from ongoing hypoxia lack regeneration PBG stem/progenitor cells. Approach Results Forty‐two patients, requiring...
Abstract Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer with marked resistance to chemotherapeutics without therapies. The tumour microenvironment of iCCA enriched Cancer-Stem-Cells expressing Epithelial-to-Mesenchymal Transition (EMT) traits, being these features associated aggressiveness and drug resistance. Treatment the anti-diabetic Metformin, has been recently reduced incidence iCCA. We aimed evaluate anti-cancerogenic effects Metformin in vitro vivo on primary...