Comparative immunogenicity study of quartet and bifurcated tetravalent dengue virus envelope domain III displayed virus-like particle vaccine candidates in BALB/c mice.

Developing an effective dengue vaccine requires targeting all four dengue virus (DENV) serotypes while ensuring both safety and efficacy. Our research aimed to address this by developing DENV vaccine candidates strategically designed to display Envelope Domain III (EDIII) antigens on a DENV capsid virus-like particle (VLP). We engineered tetravalent EDIII constructs, designed either as a quartet (qE) or bifurcated (bE) arrangement, and expressed them alongside DENV type 2 capsid (C2) in silkworm larvae, followed by affinity purification.

Cross-genotype immunogenicity and antibody-dependent enhancement of KD-382 dengue vaccine in flavivirus-naïve adults.

This exploratory study evaluated the neutralization breadth and potential antibody-dependent enhancement (ADE) risk following a single-dose of the KD-382 live-attenuated tetravalent dengue vaccine over 12 months in flavivirus-naïve healthy adults. Using single-round infectious particles representing 17 dengue virus genotypes, KD-382-induced antibodies demonstrated durable cross-genotype neutralizing activity, with minimal in vitro ADE risk. These findings highlight KD-382's potential for broad protection and underscore the importance of long-term monitoring in dengue-naïve populations.

Virus-Like Particle-Based Multiserotype Quartet Vaccine of Dengue Envelope Protein Domain III Elicited Potent Anti-Dengue Responses.

In this study, we presented two strategies for designing an envelope domain III (EDIII)-based tetravalent dengue virus (DENV) vaccine. The first approach was conjugation of the EDIIIs from all four DENV serotypes to a norovirus-like particle (NoV-LP) scaffold, yielding the NoV::tetEDIII vaccine. The second approach linked the EDIIIs of all four serotypes into a single polypeptide chain, which was also conjugated to the NoV-LP scaffold by using the SpyTag/SpyCatcher system, creating the NoV::quartetEDIII vaccine.

Heat shock protein 90 chaperone activity is required for hepatitis A virus replication.

HSP90 heat shock chaperones are essential for maintaining cellular proteostasis, as well as the ATP-dependent folding and functional maturation of many viral proteins. As a result, inhibitors of HSP90 have broad antiviral activity, disrupting replication of many viruses at concentrations below those causing cytotoxicity. Among the , HSP90 inhibitors block replication of multiple , and species, in some cases, by preventing post-translational processing and assembly of P1 capsid proteins.

Fluorescence by 5-aminolevulinic acid-induced protoporphyrin IX varies in tumor and normal tissues during robot-assisted partial nephrectomy for renal cell carcinoma.

Background: Partial nephrectomy is the gold standard for small renal cell carcinoma (RCC). Robot-assisted partial nephrectomy (RAPN), introduced in 2004, has gained acceptance as a minimally invasive approach. Determining resection margins in complex cases remains a challenge.

Application of a simple scoring scale to predict prognosis of poor-grade subarachnoid haemorrhage using intraventricular haemorrhage.

Intraventricular haemorrhage (IVH) is a key prognostic factor for subarachnoid haemorrhage (SAH). However, no simple or rapid scoring method for its evaluation exists. We aimed to modify and validate a simple scale for rapid IVH grading.

Development of neutralization tests using single-round infectious particles and cytopathic effect as an alternative method for measuring antibody titers against Japanese encephalitis virus in national epidemiological surveillance program of vaccine-preventable diseases in Japan.

The "National Epidemiological Surveillance of Vaccine-Preventable Diseases" is conducted annually in Japan for various infectious diseases. A susceptibility survey for Japanese encephalitis was conducted by measuring antibody titers using a focus-forming assay. However, this method is complicated to operate and hard to count small focuses; therefore, the development of new measurement methods is required.

Pathological characterization of female reproductive organs prior to miscarriage induced by Zika virus infection in the pregnant common marmoset.

Unlabelled: While Zika virus (ZIKV) infection in pregnant women is known to increase the risk of miscarriage and stillbirth, the mechanism by which ZIKV infection leads to the inability to continue a pregnancy is not clear. In our common marmoset models of ZIKV infection in pregnant individuals, miscarriage was observed in dams infected in the first or second trimester, and preterm delivery was observed in a dam infected in the third trimester. Serum progesterone levels were significantly lower prior to miscarriage or preterm delivery in the infected marmosets.

Tetravalent Virus-like Particles Engineered To Display Envelope Domain IIIs of Four Dengue Serotypes in Silkworm as Vaccine Candidates.

Dengue virus (DENV) causes dengue fever, the leading mosquito-borne viral disease affecting millions globally. Licensed vaccines have their restrictions, and the development of vaccines is in progress to overcome the limitations. In this study, we expressed two types of virus-like particles (VLPs) and four DENV serotype antigens, 1EDIII-4EDIII (tetEDIII), in silkworm larvae and engineered them into tetravalent VLPs (tetVLPs) displaying tetEDIII.

Seroprevalence of Hepatitis A and E virus Antibodies in Dhanusha, Madhesh Province, Nepal.

Hepatitis A virus (HAV) and hepatitis E virus (HEV) are believed to have similar routes of transmission and epidemiology in developing countries. This study investigated the seroprevalence of these pathogens among healthy individuals from the Dhanusha district of Madhesh Province, Nepal. Ninety serum samples collected between 2022 and 2023 were analyzed using enzyme-linked immunosorbent assay to detect immunoglobulin (Ig) G antibodies against HAV and HEV.

[A Case of Retroperitoneal Primary Undifferentiated Pleomorphic Sarcoma with a Rapid Course].

A 50-year-old woman presented to our hospital in May2021 with a fever of approximately39 °C and abdominal pain. A contrast-enhanced computed tomography (CT) scan revealed an 88 mm right renal tumor. Two weeks later, a follow-up CT scan demonstrated rapid tumor growth, with the major axis measuring 100 mm.

Dynamic remodeling of TRPC5 channel-caveolin-1-eNOS protein assembly potentiates the positive feedback interaction between Ca and NO signals.

The cell signaling molecules nitric oxide (NO) and Ca regulate diverse biological processes through their closely coordinated activities directed by signaling protein complexes. However, it remains unclear how dynamically the multicomponent protein assemblies behave within the signaling complexes upon the interplay between NO and Ca signals. Here we demonstrate that TRPC5 channels activated by the stimulation of G-protein-coupled ATP receptors mediate Ca influx, that triggers NO production from endothelial NO synthase (eNOS), inducing secondary activation of TRPC5 via cysteine S-nitrosylation and eNOS in vascular endothelial cells.

Importin-7-dependent nuclear translocation of the Flavivirus core protein is required for infectious virus production.

Flaviviridae is a family of positive-stranded RNA viruses, including human pathogens, such as Japanese encephalitis virus (JEV), dengue virus (DENV), Zika virus (ZIKV), and West Nile virus (WNV). Nuclear localization of the viral core protein is conserved among Flaviviridae, and this feature may be targeted for developing broad-ranging anti-flavivirus drugs. However, the mechanism of core protein translocation to the nucleus and the importance of nuclear translocation in the viral life cycle remain unknown.

Expression of dengue capsid-like particles in silkworm and display of envelope domain III of dengue virus serotype 2.

Dengue virus (DENV) is a considerable public health threat affecting millions of people globally. Vaccines for dengue are an important strategy to reduce the disease burden. We expressed capsid (C2) and envelope domain III of dengue virus serotype 2 (2EDIII) separately in the silkworm expression system.

Recent advances in hepatitis E virus research and the Japanese clinical practice guidelines for hepatitis E virus infection.

Acute hepatitis E was considered rare until reports emerged affirming the existence of hepatitis E virus (HEV) genotypes 3 and 4 infections in Japan in the early 2000s. Extensive studies by Japanese researchers have highlighted the pivotal role of pigs and wild animals, such as wild boars and deer, as reservoirs for HEV, linking them to zoonotic infections in Japan. Currently, when hepatitis occurs subsequent to the consumption of undercooked or grilled pork, wild boar meat, or offal (including pig liver and intestines), HEV infection should be considered.

Differences and Advantages of Particles versus Liquid Material for Preoperative Intracranial Tumor Embolization: A Retrospective Multicenter Study.

Objectives: The superiority and usefulness of liquid material over particles for embolization have been a topic of debate due to differences in materials and techniques. This study aimed to identify the complications and outcomes associated with both embolization materials.

Methods: This retrospective multicenter cohort study included 93 patients from an endovascular treatment registry, treated from January 1, 2018 to May 31, 2022.

Loxapine inhibits replication of hepatitis A virus in vitro and in vivo by targeting viral protein 2C.

No antiviral drugs currently are available for treatment of infection by hepatitis A virus (HAV), a causative agent of acute hepatitis, a potentially life-threatening disease. Chemical screening of a small-compound library using nanoluciferase-expressing HAV identified loxapine succinate, a selective dopamine receptor D2 antagonist, as a potent inhibitor of HAV propagation in vitro. Loxapine succinate did not inhibit viral entry nor internal ribosome entry site (IRES)-dependent translation, but exhibited strong inhibition of viral RNA replication.

Effects of thienopyridine class antiplatelets on bleeding outcomes following robot-assisted radical prostatectomy.

This study aimed to assess the effects of thienopyridine-class antiplatelet agents (including ticlopidine, clopidogrel, and prasugrel) on bleeding complications in patients who underwent robot-assisted radical prostatectomy. This cohort study used a database for robot-assisted radical prostatectomy at 23 tertiary centers nationwide between 2011 and 2022. Patients who received thienopyridines (thienopyridine group) were compared with those who received aspirin monotherapy (aspirin group).

Generation of JC Polyoma Pseudovirus for High-Throughput Measurement of Neutralizing Antibodies.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by reactivation of dormant JC polyomavirus (JCPyV). PML was mainly observed in immunocompromised individuals, such as HIV-positive patients, autoimmune disease patients, and cancer patients. Given that the presence of anti-JCPyV antibodies in serum is a risk indicator for PML development, it is essential to monitor anti-JCPyV antibody levels.

Reverse Genetics of Hepatitis C Virus Using an RNA Polymerase I-Mediated Transcription.

The reverse genetics system commonly used for the production of hepatitis C virus (HCV), which is a major causative agent of liver diseases, involves introduction of the viral genomic RNA synthesized in vitro into human hepatoma cells by electroporation. As an alternative methodology, we describe a cell culture system based on transfection with an expression plasmid containing a full-length HCV cDNA clone flanked by RNA polymerase I promoter and terminator sequences to generate infectious virus particles from transfected cells.

Role of pre-existing immunity in driving the dengue virus serotype 2 genotype shift in the Philippines: A retrospective analysis of serological data.

Objective: The invasion of dengue virus (DENV)-2 Cosmopolitan genotype into the Philippines, where the Asian II genotype previously circulated challenges the principle of dengue serotype-specific immunity. Assessment of antibodies in this population may provide a mechanistic basis for how new genotypes emerge in dengue-endemic areas.

Methods: We evaluated the neutralizing antibody (nAb) and antibody-dependent enhancement (ADE) responses against the two genotypes using archived serum samples collected from 333 patients with confirmed dengue in Metro Manila, Philippines, before, during, and after the introduction of the Cosmopolitan genotype.

Recent advances in hepatitis A virus research and clinical practice guidelines for hepatitis A virus infection in Japan.

In 2018, there was a hepatitis A outbreak in Japan, and hepatitis A virus (HAV) infection is considered a sexually transmitted disease. In general, patients with hepatitis A should be given attention, and this disease should be prevented more than ever. The Japan Agency for Medical Research and Development (AMED) Hepatitis A and E viruses (HAV and HEV) Study Group has worked on the project to create "Recent Advances in Hepatitis A Virus (HAV) Research and Clinical Practice Guidelines for HAV Infection in Japan".