NEDD4-binding protein 1 suppresses hepatitis B virus replication by regulating viral RNAs.

Chronic infection with hepatitis B virus (HBV) (chronic HBV infection) places patients at increased risk for liver cirrhosis and hepatocellular carcinoma. Although nucleos(t)ide analogues are mainly used for the treatment of HBV, they require long-term administration and may lead to the emergence of drug-resistant mutants. Therefore, to identify targets for the development of novel anti-HBV drugs, we screened for HBV-suppressive host factors using a plasmid expression library of RNA-binding proteins (RBPs).

A third dose of the BNT162b2 mRNA vaccine sufficiently improves the neutralizing activity against SARS-CoV-2 variants in liver transplant recipients.

Introduction: We examined the neutralizing antibody production efficiency of the second and third severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine doses (2- and 3-dose) and neutralizing activity on mutant strains, including, the Ancestral, Beta and Omicron strains using green fluorescent protein-carrying recombinant SARS-CoV-2, in living-donor liver transplantation (LDLT) recipients.

Methods: The patients who were administered vaccines other than Pfizer- BioNTechBNT162b2 and who had coronavirus disease 2019 in this study period were excluded. We enrolled 154 LDLT recipients and 50 healthy controls.

Bone augmentation with a prototype coral exoskeleton-derived bone replacement material applied to experimental one-wall infrabony defects created in alveolar bone.

Bone regeneration requires cells, growth factors, and scaffolds that should have biocompatibility, porosity, and physical strength. Therefore, coral granules (CG) with diameters of 600-1,000 µm were prepared as a potential graft material from cultured edaphic thermostable corals. X-ray and electron microscopy characterization revealed that CGs were porous and permeable with lumen diameters of approximately 200 µm.

Influence on Implant Bone Healing of a Collagen Membrane Placed Subjacent the Sinus Mucosa-A Randomized Clinical Trial on Sinus Floor Elevation.

Background: Perforation of the sinus mucosa is quite a frequent complication that might occur during sinus floor elevation. The perforation is often protected with a collagen membrane to avoid the extrusion of graft particles within the sinus. However, this procedure might hinder the innate osteogenic potential of the sinus mucosa.

Establishment of a Cell Culture Model Permissive for Infection by Hepatitis B and C Viruses.

Compared with each monoinfection, coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is well known to increase the risks of developing liver cirrhosis and hepatocellular carcinoma. However, the mechanism by which HBV/HCV coinfection is established in hepatocytes is not well understood. Common cell culture models for coinfection are required to examine viral propagation.

Intersubject and Intrasubject Variability of Potential Plasma and Urine Metabolite and Protein Biomarkers in Healthy Human Volunteers.

A limited understanding of intersubject and intrasubject variability hampers effective biomarker translation from in vitro/in vivo studies to clinical trials and clinical decision support. Specifically, variability of biomolecule concentration can play an important role in interpretation, power analysis, and sampling time designation. In the present study, a wide range of 749 plasma metabolites, 62 urine biogenic amines, and 1,263 plasma proteins were analyzed in 10 healthy male volunteers measured repeatedly during 12 hours under tightly controlled conditions.

Two-stage surgery for intraperitoneal and retroperitoneal multicentric liposarcoma causing hydronephrosis: a case report.

Background: Liposarcoma is a soft tissue sarcoma of adipocyte origin. Liposarcoma represents 20-30% of adult soft tissue tumors, which was most frequently seen in the retroperitoneal space in 45% and abdominal space in only 5% of cases, but the multicentric case is unknown. Herein, we describe a rare case of multicentric, large, intra-abdominal and retroperitoneal liposarcoma, one of which had caused infection and pressing the right ureter causing hydronephrosis, which was resected by two-stage surgery.

Porous Alpha-Tricalcium Phosphate with Immobilized Basic Fibroblast Growth Factor Enhances Bone Regeneration in a Canine Mandibular Bone Defect Model.

The effect of porous alpha-tricalcium phosphate (α-TCP) with immobilized basic fibroblast growth factor (bFGF) on bone regeneration was evaluated in a canine mandibular bone defect model. Identical bone defects were made in the canine mandible; six defects in each animal were filled with porous α-TCP with bFGF bound via heparin (bFGF group), whereas the other was filled with unmodified porous α-TCP (control group). Micro-computed tomography and histological evaluation were performed two, four and eight weeks after implantation.

In vivo inhibition of acylpeptide hydrolase by carbapenem antibiotics causes the decrease of plasma concentration of valproic acid in dogs.

1. Our previous in vitro studies suggest that inhibition of the acylpeptide hydrolase (APEH) activity as valproic acid glucuronide (VPA-G) hydrolase by carbapenems in human liver cytosol is a key process for clinical drug-drug interaction (DDI) of valproic acid (VPA) with carbapenems. Here, we investigated whether in vivo DDI of VPA with meropenem (MEPM) was caused via inhibition of APEH in dogs.

5th JBF Symposium: 'Bridging for a Global Harmonization'.

Tower Hall Funabori, Tokyo, Japan, 6-7 March 2014 At the 5th Japan Bioanalysis Forum symposium, distinguished bioanalytical scientists from government and industry commentated on the bioanalytical method validation guidelines/guidance issued by their own regions, including the draft bioanalytical method validation guideline for ligand binding assay by the Japanese Ministry of Health, Labour and Welfare, which was finalized in April 2014. Additionally, the Japan Bioanalysis Forum Discussion Group, in which daily bioanalytical issues/interests were scientifically discussed, picked up five topics, and more than 200 conference attendees openly exchanged their views on a wide range of bioanalytical issues with discussion group members. This manuscript provides an overview of the highlights out of the symposium.

Pharmacokinetic mechanism involved in the prolonged high retention of laninamivir in mouse respiratory tissues after intranasal administration of its prodrug laninamivir octanoate.

Laninamivir octanoate (LO) (Inavir; Daiichi Sankyo, Japan) is an ester prodrug of the neuraminidase inhibitor laninamivir. We previously reported that a prolonged high retention of laninamivir in mouse respiratory tissues was achieved by intranasal administration of LO. In this study, we evaluated intrapulmonary pharmacokinetics both in vivo and in vitro to investigate the potential mechanism involved in such a preferable retention.

Evaluation of peptide adsorption-controlled liquid chromatography-tandem mass spectrometric (PAC-LC-MS/MS) method for simple and simultaneous quantitation of amyloid β 1-38, 1-40, 1-42 and 1-43 peptides in dog cerebrospinal fluid.

To evaluate the usefulness of the peptide adsorption-controlled liquid chromatography-tandem mass spectrometry (PAC-LC-MS/MS) for reproducible measurement of peptides in biological fluids, simultaneous quantitation of amyloid β 1-38, 1-40, 1-42 and 1-43 peptides (Aβ38, Aβ40, Aβ42 and Aβ43) in dog cerebrospinal fluid (CSF) was tried. Each stable isotope labeled Aβ was used as the internal standard to minimize the influence of CSF matrix on the reproducible Aβ quantitation. To reduce a loss of Aβ during the pretreatment procedures, the dog CSF diluted by water-acetic acid-methanol (2:6:1, v/v/v) was loaded on PAC-LC-MS/MS directly.

Inhibition mechanism of carbapenem antibiotics on acylpeptide hydrolase, a key enzyme in the interaction with valproic acid.

We have reported that inhibition of acylpeptide hydrolase (APEH), identified as valproic acid glucuronide hydrolase in human liver cytosol, by carbapenem antibiotics could lead to a decrease of plasma levels of valproic acid. In this study, we examined the inhibition mechanism using human liver cytosol and purified porcine APEH with a similar property to human counterpart. After preincubation of human liver cytosol with panipenem or meropenem for 30 min, the inhibition of APEH activity was 20-fold stronger than that without preincubation.

Identification of valproic acid glucuronide hydrolase as a key enzyme for the interaction of valproic acid with carbapenem antibiotics.

Plasma levels of valproic acid (VPA) are decreased by concomitant use with carbapenem antibiotics, such as panipenem (PAPM). One of the plausible mechanisms of this interaction is the inhibition of VPA glucuronide (VPA-G) hydrolysis by carbapenems in the liver. To elucidate this interaction mechanism, we purified VPA-G hydrolase from human liver cytosol, in which the hydrolytic activity was mainly located.

Analysis of HutP-dependent transcription antitermination in the Bacillus subtilis hut operon: identification of HutP binding sites on hut antiterminator RNA and the involvement of the N-terminus of HutP in binding of HutP to the antiterminator RNA.

We investigated HutP-dependent transcription antitermination of the Bacillus subtilis hut operon. In vitro transcription assays with the B. subtilissigmaA-containing RNA polymerase indicated that HutP inhibits transcription termination at the internal terminator by binding to the antiterminator on hut mRNA in the presence of histidine.

Anti-HIV-1 activities and pharmacokinetics of new arylpiperazinyl fluoroquinolones.

Anti-HIV-1 activities and pharmacokinetics of a series of novel arylpiperazinyl fluoroquinolones are reported. Modification at the C-8 position with a trifluoromethyl group was superior to that with a difluoromethoxy group to achieve higher anti-HIV-1 activity. Two compounds studied exhibited quite high anti-HIV-1 activities (IC(50)<50 nM) in vitro and high bioavailabilities (BA>90%) in monkeys.