No abstract

In the past 50 years there have been considerable efforts to identify the cellular receptor of hepatitis B virus (HBV). Recently, in vitro evidence from several groups has shown that the sodium-taurocholate cotransporting polypeptide (NTCP, which is encoded by SLC10A1 and transports bile acids into hepatic cells in enterohepatic recirculation) is a strong candidate. In particular, in vitro the p.Ser267Phe variation of SLC10A1 results in loss of HBV receptor function. We tested the role of NTCP as a receptor for HBV in chronic hepatitis B patients using a genetic association study. We selected SLC10A1 variants from 189 exomes. We used Sanger sequencing to follow up the association of the various SLC10A1 variants in a Han Chinese cohort of 1899 chronic hepatitis B patients and 1828 healthy controls. We further investigated the potential impact of the p.Ser267-Phe variant on NTCP function using structural analysis. The p.Ser267Phe variant was associated with healthy status (P 5 5.7 3 10 223 , odds ratio 5 0.36) irrespective of hepatitis B virus surface antibody status (P 5 6.2 3 10 221 and 1.5 3 10 210 , respectively, when the cases were compared with hepatitis B virus surface antibody-positive and -negative controls). The variation was also associated with a lower incidence of acute-on-chronic liver failure (P 5 0.007). The estimated heritability explained by this single variation was 3.2%. The population prevented fraction was around 13.0% among the southern Chinese. Our structural modeling showed that the p.Ser267Phe variant might interfere with ligand binding, thereby preventing HBV from cellular entry. Conclusion: The p.Ser267Phe NTCP variant is significantly associated with resistance to chronic hepatitis B and a lower incidence of acute-on-chronic liver failure. Our results support that NTCP is a cellular receptor for HBV in human infection. (HEPATOLOGY 2015;61:1251-1260 C hronic hepatitis B (CHB) affects approximately 240 million people worldwide and is responsible for about 780,000 deaths annually (http://www.who.int/mediacentre/factsheets/fs204/en/).Clinically, CHB holds the most significant medical consequences among hepatitis B virus (HBV)-infected individuals. Acute-on-chronic liver failure (ACLF) is the most urgent and lethal condition related to CHB.Abbreviations: ACLF, acute-on-chronic liver failure; AIM, ancestry-informative marker; ASBT, apical sodium-dependent bile acid transporter; CHB, chronic hepatitis B; HBV, hepatitis B virus; HBsAb, hepatitis B virus surface antibody; HBsAg, hepatitis B virus surface antigen; HDV, hepatitis D virus; NTCP, sodiumtaurocholate cotransporting polypeptide..From the

Near-infrared (NIR) hyperthermia agents are of current interest because they hold great promise as highly efficacious tools for cancer photothermal therapy. Although various agents have been reported, a practical NIR hyperthermia agent is yet unavailable. Here, we present the first demonstration that silicon nanomaterials-based NIR hyperthermia agent, that is, gold nanoparticles-decorated silicon nanowires (AuNPs@SiNWs), is capable of high-efficiency destruction of cancer cells. AuNPs@SiNWs are found to possess strong optical absorbance in the NIR spectral window, producing sufficient heat under NIR irradiation. AuNPs@SiNWs are explored as novel NIR hyperthermia agents for photothermal ablation of tumor cells. In particular, three different cancer cells treated with AuNPs@SiNWs were completely destructed within 3 min of NIR irradiation, demonstrating the exciting potential of AuNPs@SiNWs for NIR hyperthermia agents.