Art. 1.1475/ringraziamenti

CONCLUSIONS: Anterior mandible has the highest mean bone density and posterior maxilla has the lowest mean bone density It is, therefore, proposed that an objective classification which confirms the importance of a site-specific bone tissue evaluation prior to implant installation

Cholesterol cholelithiasis in pregnant women: pathogenesis, prevention and treatment

Epidemiological and clinical studies have found that gallstone prevalence is twice as high in women as in men at all ages in every population studied. Hormonal changes occurring during pregnancy put women at higher risk. The incidence rates of biliary sludge (a precursor to gallstones) and gallstones are up to 30 and 12%, respectively, during pregnancy and postpartum, and 1-3% of pregnant women undergo cholecystectomy due to clinical symptoms or complications within the first year postpartum. Increased estrogen levels during pregnancy induce significant metabolic changes in the hepatobiliary system, including the formation of cholesterol-supersaturated bile and sluggish gallbladder motility, two factors enhancing cholelithogenesis. The therapeutic approaches are conservative during pregnancy because of the controversial frequency of biliary disorders. In the majority of pregnant women, biliary sludge and gallstones tend to dissolve spontaneously after parturition. In some situations, however, the conditions persist and require costly therapeutic interventions. When necessary, invasive procedures such as laparoscopic cholecystectomy are relatively well tolerated, preferably during the second trimester of pregnancy or postpartum. Although laparoscopic operation is recommended for its safety, the use of drugs such as ursodeoxycholic acid (UDCA) and the novel lipid-lowering compound, ezetimibe would also be considered. In this paper, we systematically review the incidence and natural history of pregnancy-related biliary sludge and gallstone formation and carefully discuss the molecular mechanisms underlying the lithogenic effect of estrogen on gallstone formation during pregnancy. We also summarize recent progress in the necessary strategies recommended for the prevention and the treatment of gallstones in pregnant women

Structural Model Reveals Key Interactions in the Assembly of the Pregnane X Receptor/Corepressor Complex Running Title: Molecular Dynamics of PXR-SMRT Interactions

Abstract The human pregnane X receptor (PXR), also known as steroid and xenobiotic receptor (SXR), is a member of the orphan nuclear receptors and mediates the mammalian xenobiotic response with broad specificity and implications for drug clearance. The mouse pregnane X receptor is highly similar to the human ortholog in structure but with subtle species differentiation in the ligand binding domain (LBD). The C-terminal helix named α AF or AF-2 helix in other nuclear receptors is responsible for transcription activation by recruiting co-activators through conformational change. In the absence of ligands, PXR can also repress gene expression by interacting with transcriptional corepressors such as the silencing mediator for retinoid and thyroid hormone receptor (SMRT). We first constructed homology models of completed LBD with two SMRT nuclear receptor (NR)-interacting domains (ID1 and ID2) respectively. We then performed energy minimization and molecular dynamics simulations on these systems to study the specific interactions between the interacting domains and LBD. Further experimental results supported and validated the observed preference of SMRT toward ID2 over ID1. Our modeling results revealed the key interactions that account for the binding preference. Here, we propose structural models of the PXR-LBD/SMRT-ID1 and PXR-LBD/SMRT-ID2 complexes to understand their molecular interactions and potential inhibitory mechanism

Structural Model Reveals Key Interactions in the Assembly of the Pregnane X Receptor/Corepressor Complex Running Title: Molecular Dynamics of PXR-SMRT Interactions

Abstract The human pregnane X receptor (PXR), also known as steroid and xenobiotic receptor (SXR), is a member of the orphan nuclear receptors and mediates the mammalian xenobiotic response with broad specificity and implications for drug clearance. The mouse pregnane X receptor is highly similar to the human ortholog in structure but with subtle species differentiation in the ligand binding domain (LBD). The C-terminal helix named α AF or AF-2 helix in other nuclear receptors is responsible for transcription activation by recruiting co-activators through conformational change. In the absence of ligands, PXR can also repress gene expression by interacting with transcriptional corepressors such as the silencing mediator for retinoid and thyroid hormone receptor (SMRT). We first constructed homology models of completed LBD with two SMRT nuclear receptor (NR)-interacting domains (ID1 and ID2) respectively. We then performed energy minimization and molecular dynamics simulations on these systems to study the specific interactions between the interacting domains and LBD. Further experimental results supported and validated the observed preference of SMRT toward ID2 over ID1. Our modeling results revealed the key interactions that account for the binding preference. Here, we propose structural models of the PXR-LBD/SMRT-ID1 and PXR-LBD/SMRT-ID2 complexes to understand their molecular interactions and potential inhibitory mechanism