A5063803893- Neonatal Health and Biochemistry
- Heme Oxygenase-1 and Carbon Monoxide
- Liver physiology and pathology
- Methemoglobinemia and Tumor Lysis Syndrome
- Metabolism and Genetic Disorders
- Pancreatic function and diabetes
- Drug Transport and Resistance Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Erythrocyte Function and Pathophysiology
- Pediatric Hepatobiliary Diseases and Treatments
- Clinical Nutrition and Gastroenterology
- Biomedical Research and Pathophysiology
- Autophagy in Disease and Therapy
- Cancer-related gene regulation
- Hemoglobinopathies and Related Disorders
- Liver Disease Diagnosis and Treatment
- Neuroscience and Neuropharmacology Research
- Medical Imaging Techniques and Applications
- Mitochondrial Function and Pathology
- Hemoglobin structure and function
- Aldose Reductase and Taurine
- Organ Transplantation Techniques and Outcomes
- Advanced Radiotherapy Techniques
- Genetic and Kidney Cyst Diseases
- Radiopharmaceutical Chemistry and Applications
Fondazione Italiana Fegato
2013-2025
International Flame Research Foundation
2013-2025
AREA Science Park
2003-2022
University of Trieste
2003-2012
Null mutations in the UGT1A1 gene result Crigler–Najjar syndrome type I (CNSI), characterized by severe hyperbilirubinemia and constant risk of developing neurological damage. Phototherapy treatment lowers plasma bilirubin levels, but its efficacy is limited liver transplantation required. To find alternative therapies, we applied AAV liver-specific therapy to a lethal mouse model CNSI. We demonstrated that single neonatal hUGT1A1 transfer was successful therapeutic effect lasted up 17...
Crigler-Najjar type I (CNI) syndrome is a recessively inherited disorder characterized by severe unconjugated hyperbilirubinemia caused uridine diphosphoglucuronosyltransferase 1A1 (UGT1A1) deficiency. The disease lethal due to bilirubin-induced neurological damage unless phototherapy applied from birth. However, treatment becomes less effective during growth, and liver transplantation required. To investigate the pathophysiology of therapeutic approaches in mice, we generated mouse model...
<b><i>Background:</i></b> Severe neonatal hyperbilirubinemia, with consequent encephalopathy, remains a common cause of morbidity and death in many regions the world. Poor access to clinical laboratory resources screening programs measure plasma bilirubin levels is major contributor delayed treatment developing countries, cost existing point-of-care instruments precludes their dissemination. <b><i>Objectives:</i></b> We are evaluating accuracy...
Neonatal hyperbilirubinemia may result in long-lasting motor, auditory and learning impairments. The mechanisms responsible for the localization of unconjugated bilirubin (UCB) to specific brain areas as well those involved potentially permanent central nervous system (CNS) dysfunctions are far from being clear. One area investigation includes exploring how determines neuronal alterations predisposing neurodevelopmental disorders. We focused on hippocampus pyramidal cell dysregulation...
Introduction: Research of hepatic diseases needs a suitable model that mimics the function and structure liver. Organoids have special ability to self-organize in 3D recreates physiological conditions organ origin. can be derived from pluripotent stem cells or adult differentiated primary cells. Protocols obtain organoids recapitulate main stages embryonic liver development, while ones starting hepatocytes (Hep-Orgs) recreate environment occurring during partial hepatectomy, where are...
Background: Severe hyperbilirubinemia can cause permanent neurological damage in particular neonates, whereas mildly elevated serum bilirubin protects from various oxidative stress-mediated diseases. The present work aimed to establish the intracellular unconjugated concentrations (iUCB) thresholds differentiating between anti- and pro-oxidant effects. Methods: Hepatic (HepG2), heart endothelial (H5V), kidney tubular (HK2) neuronal (SH-SY5Y) cell lines were exposed increasing concentration...
We have previously reported that exposure of SH-SY5Y neuroblastoma cells to unconjugated bilirubin (UCB) resulted in a marked up-regulation the mRNA encoding for Na+ -independent cystine∶glutamate exchanger System Xc− (SLC7A11 and SLC3A2 genes). In this study we demonstrate treated with UCB showed higher cystine uptake due significant specific increase activity Xc−, without contribution others two transporters (XAG− GGT) neurons. The total intracellular glutathione content was 2 folds...
Abstract Unconjugated bilirubin (UCB) is a powerful antioxidant and modulator of cell growth through the interaction with several signal transduction pathways. Although newborns develop physiological jaundice, in case severe hyperbilirubinemia UCB may become neurotoxic causing long‐term neuronal damages, also known as encephalopathy. To investigate mechanisms UCB‐induced toxicity, we used human neuroblastoma line SH‐SY5Y an vitro model system. We verified that caused death, part due to...
Programmed cell death is characterized by posttranslational modifications of a limited and specific set nuclear proteins. We demonstrate that during apoptosis different types tumor cells there monomethylation the protein HMGA1a associated to its previously described hyperphosphorylation/dephosphorylation process. methylation strictly related execution programmed massive event involves large amounts protein. In some cells, already methylated an extent depends on type. The degree in any case...
Abstract Background The deposition of unconjugated bilirubin (UCB) in selected regions the brain results irreversible neuronal damage, or Bilirubin Encephalopathy (BE). Although UCB impairs a large number cellular functions other tissues, basic mechanisms neurotoxicity have not yet been fully clarified. While cells can accumulate by passive diffusion, cell protection may involve multiple including extrusion pigment as well pro-survival homeostatic responses that are still unknown. Results...
As in adults, obesity also plays a central role the development of metabolic syndrome (MS) children. Non-alcoholic fatty liver disease (NAFLD) is considered manifestation MS. Not only MS but NAFLD seem to be inversely associated with serum bilirubin concentrations, an important endogenous tissue protector when mild elevated. The aim study was evaluate association between levels and prevalence Italian obese children adolescents. A retrospective cross-sectional performed 1672 patients aged...
In vitro and in vivo studies have demonstrated that UCB (unconjugated bilirubin) is neurotoxic. Although previous suggested both MRP1 (multidrug resistance-associated protein 1) MDR1 resistance may protect cells against accumulation of UCB, direct comparison their role transport was never performed. To this end, we used an inducible siRNA (small interfering RNA) expression system to silence the human neuroblastoma SH-SY5Y cells. The effects exposure clinically-relevant levels unbound were...