Prediction of cccDNA dynamics in hepatitis B patients by a combination of serum surrogate markers.

Quantification of intrahepatic covalently closed circular DNA (cccDNA) is a key for evaluating an elimination of hepatitis B virus (HBV) in infected patients. However, quantifying cccDNA requires invasive methods such as a liver biopsy, which makes it impractical to access the dynamics of cccDNA in patients. Although HBV RNA and HBV core-related antigens (HBcrAg) have been proposed as surrogate markers for evaluating cccDNA activity, they do not necessarily estimate the amount of cccDNA.

Giant Sialolithiasis in Submandibular Gland Growing over Extended Period: A Case Report.

Sialolithiasis is a common disease of the salivary glands. This report describes a rare case of a submandibular gland sialolithiasis that grew over an extended period. The patient was a 72-year-old woman who presented with a mass in the right submandibular gland that had remained untreated for approximately 34 years.

Multiscale modeling of HBV infection integrating intra- and intercellular viral propagation to analyze extracellular viral markers.

Chronic infection with hepatitis B virus (HBV) is caused by the persistence of closed circular DNA (cccDNA) in the nucleus of infected hepatocytes. Despite available therapeutic anti-HBV agents, eliminating the cccDNA remains challenging. Thus, quantifying and understanding the dynamics of cccDNA are essential for developing effective treatment strategies and new drugs.

Selective inhibition of hepatitis B virus internalization by oxysterol derivatives.

Given that the current approved anti-hepatitis B virus (HBV) drugs suppress virus replication and improve hepatitis but cannot eliminate HBV from infected patients, new anti-HBV agents with different mode of action are urgently needed. In this study, we identified a semi-synthetic oxysterol, Oxy185, that can prevent HBV infection in a HepG2-based cell line and primary human hepatocytes. Mechanistically, Oxy185 inhibited the internalization of HBV into cells without affecting virus attachment or replication.

Multiscale modeling of HBV infection integrating intra- and intercellular viral propagation for analyzing extracellular viral markers.

Chronic infection of hepatitis B virus (HBV) is caused by the persistence of closed circular DNA (cccDNA) in the nucleus of infected hepatocytes. Despite available therapeutic anti-HBV agents, eliminating the cccDNA remains challenging. The quantifying and understanding dynamics of cccDNA are essential for developing effective treatment strategies and new drugs.

Second Primary Metachronous Malignancies Occurring in Oral Cavity of Young Adult-A Case Report.

The incidence of oral cancer in Japan is increasing. Interestingly, the number of young patients with oral cancer is also rising. A 19-year-old man with no history of smoking or drinking alcohol presented with a 20×15-mm elastic, hard, protruding mass with a white surface on the right-hand margin of the tongue.

Structural insights into the HBV receptor and bile acid transporter NTCP.

Around 250 million people are infected with hepatitis B virus (HBV) worldwide, and 15 million may also carry the satellite virus hepatitis D virus (HDV), which confers even greater risk of severe liver disease. The HBV receptor has been identified as sodium taurocholate co-transporting polypeptide (NTCP), which interacts directly with the first 48 amino acid residues of the N-myristoylated N-terminal preS1 domain of the viral large protein. Despite the pressing need for therapeutic agents to counter HBV, the structure of NTCP remains unsolved.

Fungal Secondary Metabolite Exophillic Acid Selectively Inhibits the Entry of Hepatitis B and D Viruses.

Current anti-hepatitis B virus (HBV) drugs are suppressive but not curative for HBV infection, so there is considerable demand for the development of new anti-HBV agents. In this study, we found that fungus-derived exophillic acid inhibits HBV infection with a 50% maximal inhibitory concentration (IC50) of 1.1 µM and a 50% cytotoxic concentration (CC50) of >30 µM in primary human hepatocytes.

Identification of novel avian and mammalian deltaviruses provides new insights into deltavirus evolution.

Hepatitis delta virus (HDV) is a satellite virus that requires hepadnavirus envelope proteins for its transmission. Although recent studies identified HDV-related deltaviruses in certain animals, the evolution of deltaviruses, such as the origin of HDV and the mechanism of its coevolution with its helper viruses, is unknown, mainly because of the phylogenetic gaps among deltaviruses. Here, we identified novel deltaviruses of passerine birds, woodchucks, and white-tailed deer by extensive database searches and molecular surveillance.

Countermeasure and opportunistic screening systems for oral cancer.

Objectives: Tokyo Dental College started oral cancer screening in cooperation with a local dental association in 1992. Reveal the usefulness of Countermeasure and Opportunistic Screening Systems for Oral Cancer. The actual results of countermeasure and opportunistic oral cancer screening systems are reported.

Impact of Immune Reconstitution-Induced Hepatic Flare on Hepatitis B Surface Antigen Loss in Hepatitis B Virus/Human Immunodeficiency Virus-1 Coinfected Patients.

Background: Hepatitis B surface antigen (HBsAg) loss is an ideal goal for chronic hepatitis B patients. Antiretroviral therapy (ART) in hepatitis B virus/human immunodeficiency virus-1 (HBV/HIV-1)-coinfected patients can lead to hepatic flare (HF) caused by immune reconstitution-induced inflammatory syndrome (IRIS). Here, we investigated the impact of IRIS-HF on HBsAg loss.

Utilization of desktop 3D printer-fabricated "Cost-Effective" 3D models in orthognathic surgery.

Background: In daily practice, three-dimensional patient-specific jawbone models (3D models) are a useful tool in surgical planning and simulation, resident training, patient education, and communication between the physicians in charge. The progressive improvements of the hardware and software have made it easy to obtain 3D models. Recently, in the field of oral and maxillofacial surgery, there are many reports on the benefits of 3D models.

N-Terminal PreS1 Sequence Regulates Efficient Infection of Cell-Culture-Generated Hepatitis B Virus.

Background And Aims: An efficient cell-culture system for hepatitis B virus (HBV) is indispensable for research on viral characteristics and antiviral reagents. Currently, for the HBV infection assay in cell culture, viruses derived from HBV genome-integrated cell lines of HepG2.2.

Investigation of Surgical Site Infections and Bacteria Detected Following Neck Dissection in Patients with Oral Cancer.

During dissection for oral cancer, there is a high probability of bacteria indigenous to the oral cavity migrating to the surgical field in the neck due to the opening of new pathways of communication with the oral cavity. The risk of postoperative surgical site infection (SSI) in such patients is high due to malnutrition arising from perioperative eating disorders and dysphagia. Neck infections after neck dissection in oral cancer patients were investigated to elucidate the development of SSIs and their relationship with the results of bacterial culture.

The machinery for endocytosis of epidermal growth factor receptor coordinates the transport of incoming hepatitis B virus to the endosomal network.

Sodium taurocholate cotransporting polypeptide (NTCP) is expressed at the surface of human hepatocytes and functions as an entry receptor of hepatitis B virus (HBV). Recently, we have reported that epidermal growth factor receptor (EGFR) is involved in NTCP-mediated viral internalization during the cell entry process. Here, we analyzed which function of EGFR is essential for mediating HBV internalization.

Anti-viral effects of interferon-λ3 on hepatitis B virus infection in cell culture.

Aim: Interferon (IFN)-λ3 is known to have antiviral effects against various pathogens. Recently, it has been reported that the production of IFN-λ3 in colon cells after the administration of nucleotide analogs is expected to reduce hepatitis B surface antigen in chronic hepatitis B patients. Here, we aimed to prove the antiviral effects of IFN-λ3 on hepatitis B virus (HBV) by using an in vitro HBV production and infection system.

Synthesis of nucleotide analogues, EFdA, EdA and EdAP, and the effect of EdAP on hepatitis B virus replication.

4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) and 4'-ethynyl-2'-deoxyadenosine (EdA) are nucleoside analogues which inhibit human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. EdAP, a cyclosaligenyl (cycloSal) phosphate derivative of EdA, inhibits the replication of the influenza A virus. The common structural feature of these compounds is the ethynyl group at the 4'-position.

Epidermal growth factor receptor is a host-entry cofactor triggering hepatitis B virus internalization.

Sodium taurocholate cotransporting polypeptide (NTCP) is a host cell receptor required for hepatitis B virus (HBV) entry. However, the susceptibility of NTCP-expressing cells to HBV is diverse depending on the culture condition. Stimulation with epidermal growth factor (EGF) was found to potentiate cell susceptibility to HBV infection.

Prognostic factors for maxillary sinus mucosal thickening following Le Fort I osteotomy: a retrospective analysis.

Background: Le Fort I osteotomy is one of the surgical procedures now routinely and safely performed. It is possible to move the maxilla in three dimensions, but it is necessary to separate the bones around the maxillary sinus. Therefore, with surgery, maxillary sinus mucosal thickening occurs.

Functional association of cellular microtubules with viral capsid assembly supports efficient hepatitis B virus replication.

Viruses exploit host factors and environment for their efficient replication. The virus-host interaction mechanisms for achieving an optimal hepatitis B virus (HBV) replication have been largely unknown. Here, a single cell cloning revealed that HepAD38 cells, a widely-used HBV-inducible cell line, contain cell clones with diverse permissiveness to HBV replication.

Cyclosporin derivatives inhibit hepatitis B virus entry without interfering with NTCP transporter activity.

Background & Aims: The sodium taurocholate co-transporting polypeptide (NTCP) is the main target of most hepatitis B virus (HBV) specific entry inhibitors. Unfortunately, these agents also block NTCP transport of bile acids into hepatocytes, and thus have the potential to cause adverse effects. We aimed to identify small molecules that inhibit HBV entry while maintaining NTCP transporter function.

A new class of hepatitis B and D virus entry inhibitors, proanthocyanidin and its analogs, that directly act on the viral large surface proteins.

Unlabelled: Introduction of direct-acting antivirals against hepatitis C virus (HCV) has provided a revolutionary improvement in the treatment outcome. In contrast to HCV, however, the strategy for developing new antiviral agents against hepatitis B virus (HBV), especially viral-targeting compounds, is limited because HBV requires only four viral genes for its efficient replication/infection. Here, we identify an oligomeric flavonoid, proanthocyanidin (PAC) and its analogs, which inhibit HBV entry into host cells by targeting the HBV large surface protein (LHBs).

Anti-hepatitis C Virus Natural Product from a Fungus, Penicillium herquei.

New diazabicyclo[2.2.2]octane derivatives, peniciherquamides A-C (1-3), and a novel herqueinone derivative, neoherqueinone (5), were isolated from a fungal culture broth of Penicillium herquei.