“Vitamin D3 improves portal hypertension (PH) through the activation of vitamin D receptor (VDR) and calcium
sensing receptor (CaSR) in cirrhotic rats. Propranolol is a nonselective β–blocker that is recommended for the treatment of PH. The present study aims to investigate the detail systemic and hepatic mechanisms of vitamin D3 and propranolol, alone or in combination, in cirrhotic rats. Common bile duct-ligated (BDL) and thioacetamide (TAA) cirrhotic rats were treated with vehicle, propranolol (30mg.kg-1.day-1), vitamin D3 (0.5μg.100g-1.day-1, twice weekly), or propranolol+ selleck compound vitamin D3, separately. Significantly, propranolol and vitamin D3 produced a similar magnitude of reduction in portal venous pressure (PVP) in cirrhotic rats through different mechanisms: whereas propranolol decreased PVP by reducing splanchnic hyperemia and cardiac index, vitamin D3 decreased PVP by decreasing intrahepatic resistance (IHR). However, propranolol plus vitamin D3 did not further decrease PVP in cirrhotic rats. Notably, a marked decrease in hepatic VDR and CaSR expressions was noted in cirrhotic human/rat livers compared to non-cirrhotic human/rat livers. In cirrhotic rats, vitamin D3 administration decreasing IHR by inhibiting the renin-angiotensin system, hepatic oxidative stress, inflammation/fibrosis,
ANGII production, Venetoclax purchase CaSR-mediated angiotensin II (ANGII) hyper-responsiveness, ANGII-induced hepatic stellate cells contraction, and correcting hepatic endothelial dysfunction through up-regulation of hepatic VDR, CaSR and eNOS expressions. Chronic vitamin D3 treatment alone results in comparative
portal hypotensive effects as propranolol alone in cirrhotic rats with PH. Taken together, chronic vitamin D3 administration was an ideal alternative strategy to effectively improve PH without unwanted systemic side effects. “
“Chronic hepatitis B (CHB) is a major global health issue. The role of rare genetic variants in CHB has not been elucidated. We aimed to identify rare allelic variants predisposing to CHB. We performed exome sequencing in 50 CHB patients who had no identifiable risk factors for CHB selleck and 40 controls who were healthy and hepatitis B surface antibody-positive, but had never received hepatitis B vaccination. We selected six rare variant alleles and followed up their association with disease status by Sanger sequencing in a case-control study comprising 1,728 CHB patients and 1,636 healthy controls. The latter had either not been immunized with hepatitis B vaccine or had uncertain vaccination status. Our results showed that transmembrane protein 2 p.Ser1254Asn, interferon alpha 2 p.Ala120Thr, its regulator NLR family member X1 p.Arg707Cys, and complement component 2 p.Glu318Asp were associated with CHB, with P values of <1.0 × 10−7, 2.76 × 10−5, 5.08 × 10−5, 2.