Publications by authors named "Rina Hashimoto"

The recent emergence and global spread of the mpox virus (MPXV), formerly known as the monkeypox virus, underscores the urgent need for effective antiviral materials to combat this emerging zoonotic pathogen. This study evaluates the antiviral activity of five functional material films against vaccinia virus, a representative model of MPXV, by the TCID50 assay. The tested materials include two electrospun polyester fabrics functionalised with benzalkonium chloride (BAK) or soap, specifically designed for antiviral face masks.

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Vaccines effectively stimulate protective immune responses in healthy individuals, but the precise roles of germinal center (GC) and follicular helper T (TFH) cells in SARS-CoV-2 vaccine responses are not fully understood. This study used a conditional loss-of-function mouse model to investigate antibody responses to the Wuhan spike protein, specifically eliminating newly developed TFH cells during either the primary or memory phase. Our findings demonstrated that TFH-mediated GC responses are essential for primary vaccination.

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The genome of human coronavirus 229E (HCoV-229E), a causative agent of human respiratory infections, encodes a unique accessory gene, ORF4. Analysis of laboratory strains and clinical specimens has suggested that HCoV-229E acquires truncating mutations in ORF4 under standard laboratory culture conditions. This study confirmed that HCoV-229E from patients with acute respiratory infections harboured a full-length ORF4 (219 amino acids).

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Introduction: Adult intussusception is rare, accounting for approximately 5%-16% of all cases. Unlike pediatric intussusception, which is predominantly idiopathic, most adult cases are associated with organic lesions, nearly half of which are malignant. Idiopathic intussusception without a lead point is uncommon but appears to be increasingly recognized.

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Respiratory syncytial virus (RSV) is a seasonal respiratory pathogen that primarily affects young children, potentially causing severe lower respiratory tract disease. Despite the high disease burden, understanding of RSV pathophysiology remains limited. To address this, advanced RSV infection models are needed.

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Background: Longitudinal studies investigating cognitive function changes in patients with progressive supranuclear palsy (PSP) are limited. The variability of cognitive impairment across clinical subtypes of PSP remains unclear.

Objective: This study aimed to compare the longitudinal changes in cognitive function between patients with PSP and Parkinson's disease (PD) and to assess differences in cognitive impairment among PSP subtypes.

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Article Synopsis
  • - Advanced cell culture systems like human induced pluripotent stem (iPS) cells and organoids are being used to create complex organ models for studying diseases, including those caused by viruses such as SARS-CoV-2.
  • - Researchers developed innovative alveolar and airway models with a specialized 'apical-out' structure to better understand how respiratory cells respond to SARS-CoV-2 infection, revealing important cell types like type II alveolar epithelial and ciliated cells.
  • - These new models enable the analysis of different variants of SARS-CoV-2 and can potentially be used to study a variety of respiratory viruses beyond COVID-19.
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Unlabelled: A critical aspect of the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the protease-mediated activation of the viral spike (S) protein. The type II transmembrane serine protease TMPRSS2 is crucial for SARS-CoV-2 infection in lung epithelial Calu-3 cells and murine airways. However, the importance of TMPRSS2 needs to be re-examined because the ability to utilize TMPRSS2 is significantly reduced in the Omicron variants that spread globally.

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Neutrophil extracellular traps (NETs), essential for controlling infections, can induce various pathologies when dysregulated. Known triggers for infection-independent NETs release exist, yet a comprehensive understanding of the conditions prompting such responses is lacking. In this study, we identify hyponatremia as an independent inducer of NETs release, a common clinical condition that disrupts sodium/calcium exchange within neutrophils.

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Article Synopsis
  • Emerging respiratory viruses like SARS-CoV-2 pose a global risk, prompting the need for new antiviral strategies, particularly through the use of gapmer antisense oligonucleotides (ASOs).
  • Researchers synthesized about 300 ASOs targeting different regions of the SARS-CoV-2 RNA and effectively identified ASO#41, which inhibited viral replication and reduced infection-related cell damage.
  • ASO#41 demonstrated strong antiviral activity against multiple variants of SARS-CoV-2 in lab models and showed promise in mice, indicating its potential as a targeted treatment approach for respiratory viruses.
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  • Researchers isolated a coronavirus called BANAL-20-236 (B236) from Malayan horseshoe bats and found it lacks a key site in its spike protein that is present in SARS-CoV-2.
  • * They compared B236's characteristics using human-derived cells and hamster infection experiments, discovering it's less pathogenic and grows slower in respiratory cells compared to SARS-CoV-2, but grows better in intestinal cells.
  • * The study suggests that SC2r-CoVs like B236 may primarily replicate in the intestines rather than the respiratory system, supporting prior findings about its behavior in other models.
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A primary reason for the ongoing spread of coronavirus disease 2019 (COVID-19) is the continuous acquisition of mutations by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the mechanism of acquiring mutations is not fully understood. In this study, we isolated SARS-CoV-2 from an immunocompromized patient persistently infected with Omicron strain BF.

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The emergence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) variants necessitated a rapid evaluation system for their pathogenesis. Lung epithelial cells are their entry points; however, in addition to their limited source, the culture of human alveolar epithelial cells is especially complicated. Induced pluripotent stem cells (iPSCs) are an alternative source of human primary stem cells.

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Lysosomal degradation of tyrosinase, a pivotal enzyme in melanin synthesis, negatively impacts melanogenesis in melanocytes. Nevertheless, the precise molecular mechanisms by which lysosomes target tyrosinase have remained elusive. Here, we identify RING (Really Interesting New Gene) finger protein 152 (RNF152) as a membrane-associated ubiquitin ligase specifically targeting tyrosinase for the first time, utilizing AlphaScreen technology.

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Article Synopsis
  • The emergence of a new Variant of Interest, XBB.1.5, is linked to mutations from the pre-existing variant XBB.1, specifically an S486P spike mutation and a nonsense mutation in ORF8.
  • Phylogenetic analysis indicates that XBB.1.5 maintains similar immune escape abilities compared to XBB.1, and structural studies reveal that the spike proteins of both variants are largely similar.
  • Research involving hamsters shows that the ORF8 nonsense mutation in XBB.1.5 reduces MHC suppression and results in lower virulence in this variant compared to XBB.1.
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  • - The emergence of the Omicron subvariant BA.5 of SARS-CoV-2 requires urgent investigation due to its rapid spread and the need for ongoing control measures.
  • - BA.5 exhibits enhanced fusogenicity and a greater ability to disrupt respiratory barriers compared to earlier subvariants BA.1 and BA.2, even though its in vitro growth rates are similar.
  • - In a hamster model, BA.5 shows slightly higher pathogenicity than other Omicron variants but less than the ancestral strain, along with improved virus spread and immune response activation.
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The outbreak-causing monkeypox virus of 2022 (2022 MPXV) is classified as a clade IIb strain and phylogenetically distinct from prior endemic MPXV strains (clades I or IIa), suggesting that its virological properties may also differ. Here, we used human keratinocytes and induced pluripotent stem cell-derived colon organoids to examine the efficiency of viral growth in these cells and the MPXV infection-mediated host responses. MPXV replication was much more productive in keratinocytes than in colon organoids.

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Background: Several genetic factors are associated with the pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) and its phenotypes, such as disease progression. Here, in this study, we aimed to identify the genes that affect the survival of patients with sporadic ALS.

Methods: We enrolled 1076 Japanese patients with sporadic ALS with imputed genotype data of 7 908 526 variants.

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To deal with the broad spectrum of coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that threaten human health, it is essential to not only drugs develop that target viral proteins but also consider drugs that target host proteins/cellular processes to protect them from being hijacked for viral infection and replication. To this end, it has been reported that autophagy is deeply involved in coronavirus infection. In this study, we used airway organoids to screen a chemical library of autophagic modulators to identify compounds that could potentially be used to fight against infections by a broad range of coronaviruses.

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SARS-CoV-2 induces severe organ damage not only in the lung but also in the liver, heart, kidney, and intestine. It is known that COVID-19 severity correlates with liver dysfunction, but few studies have investigated the liver pathophysiology in COVID-19 patients. Here, we elucidated liver pathophysiology in COVID-19 patients using organs-on-a-chip technology and clinical analyses.

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Background: As SARS-CoV-2 continues to mutate into Variants of Concern (VOC), there is growing and urgent need to develop effective antivirals to combat COVID-19. Monoclonal antibodies developed earlier are no longer capable of effectively neutralizing currently active VOCs. This report describes the design of variant-agnostic chimeric molecules consisting of an Angiotensin-Converting Enzyme 2 (ACE-2) domain mutated to retain ultrahigh affinity binding to a wide variety of SARS-CoV-2 variants, coupled to an Fc-silent immunoglobulin domain that eliminates antibody-dependent enhancement and extends biological half-life.

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Article Synopsis
  • There is an urgent need for new drugs to combat severe infectious diseases, such as COVID-19, as current treatments do not fully reduce mortality rates.
  • The study focuses on a protein called Robo4, which stabilizes endothelial cells and decreases vascular permeability, showing that increasing its expression may help reduce death rates in cases of severe infection.
  • Researchers found that a specific inhibitor could effectively boost Robo4 levels in the lungs and protect against both LPS-induced inflammation and SARS-CoV-2 infection, suggesting small molecules that enhance Robo4 could be promising therapeutic options.
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Article Synopsis
  • - The study investigates host factors that are crucial for SARS-CoV-2 infection, focusing on components beyond just receptors and proteases, using iPS cells and airway organoids.
  • - Researchers identified EXOC2 as a key host factor; when EXOC2 was knocked down, the intracellular levels of the virus dropped significantly, indicating its importance in viral infection.
  • - The findings suggest that EXOC2 knockdown reduces SARS-CoV-2 infection by affecting the expression of IFNW1, highlighting its potential as a target for preventing the virus and warranting further research.
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In the initial process of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects respiratory epithelial cells and then transfers to other organs the blood vessels. It is believed that SARS-CoV-2 can pass the vascular wall by altering the endothelial barrier using an unknown mechanism. In this study, we investigated the effect of SARS-CoV-2 on the endothelial barrier using an airway-on-a-chip that mimics respiratory organs and found that SARS-CoV-2 produced from infected epithelial cells disrupts the barrier by decreasing Claudin-5 (CLDN5), a tight junction protein, and disrupting vascular endothelial cadherin-mediated adherens junctions.

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