563 results match your criteria: "Institute of Biomedical Research and Innovation.[Affiliation]"

HDAC7 is a potential therapeutic target in acute erythroid leukemia.

Leukemia

December 2024

Division of Molecular Oncology, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.

Acute erythroleukemia (AEL) is a rare subtype of acute myeloid leukemia with a poor prognosis. In this study, we established a novel murine AEL model with Trp53 depletion and ERG overexpression. ERG overexpression in Trp53-deficient mouse bone marrow cells, but not in wild-type bone marrow cells, leads to AEL development within two months after transplantation with 100% penetrance.

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Structural variations involving enhancer hijacking induce aberrant oncogene expression and cause tumorigenesis. A rare translocation, t(3;8)(q26.2;q24), is associated with MECOM and MYC rearrangement, causing myeloid neoplasms with a dismal prognosis.

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Anti-SARS-CoV-2 gapmer antisense oligonucleotides targeting the main protease region of viral RNA.

Antiviral Res

October 2024

Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo, 162-8640, Japan; Department of Virology II, National Institute of Infectious Diseases, Tokyo, 162-8640, Japan; Department of Applied Biological Sciences, Tokyo University of Science, Noda, 278-8510, J

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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SETDB1 suppresses NK cell-mediated immunosurveillance in acute myeloid leukemia with granulo-monocytic differentiation.

Cell Rep

August 2024

Division of Molecular Oncology, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo 108-8639, Japan. Electronic address:

Monocytic acute myeloid leukemia (AML) responds poorly to current treatments, including venetoclax-based therapy. We conducted in vivo and in vitro CRISPR-Cas9 library screenings using a mouse monocytic AML model and identified SETDB1 and its binding partners (ATF7IP and TRIM33) as crucial tumor promoters in vivo. The growth-inhibitory effect of Setdb1 depletion in vivo is dependent mainly on natural killer (NK) cell-mediated cytotoxicity.

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Background: Cardiac rehabilitation is fundamental among patients recovering from a coronary event, and mHealth technology may constitute a useful tool that provides guidelines based on scientific evidence in an entertaining, attractive, and user-friendly format.

Objective: This study aimed to compare the efficacy of an mHealth intervention involving the eMOTIVA app and that of usual care regarding compliance with cardiac rehabilitation guidelines in terms of lifestyle, cardiovascular risk factors, and satisfaction among patients with acute coronary syndrome.

Methods: A randomized controlled clinical trial with a parallel group design was conducted.

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Article Synopsis
  • In the 2010s, new rotavirus strains led to global epidemics, prompting a study in Japan that analyzed 489 rotavirus-positive stool samples from 2014 to 2019 using next-generation sequencing.
  • Nine different rotavirus genotypes were identified, with the dominant strain changing each year; notable strains included G8P[8] and G1P[8] in the early years, and G9P[8] becoming prevalent in 2016 and 2019.
  • The study revealed that certain strains, particularly G1P[8]-E2, may have emerged from independent genetic reassortment events and exhibited distinct mutations in VP7 proteins, which could help the virus evade immune
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Over the last few decades, the implementation of pharmacogenomics (PGx) in clinical practice has improved tailored drug prescriptions [...

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Enteroviruses are single-stranded, positive-sense RNA viruses causing endoplasmic reticulum (ER) stress to induce or modulate downstream signaling pathways known as the unfolded protein responses (UPR). However, viral and host factors involved in the UPR related to viral pathogenesis remain unclear. In the present study, we aimed to identify the major regulator of enterovirus-induced UPR and elucidate the underlying molecular mechanisms.

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Background: Increased levels of plasminogen activator inhibitor-1 (PAI-1) in tumors have been found to correlate with poor clinical outcomes in patients with cancer. Although abundant data support the involvement of PAI-1 in cancer progression, whether PAI-1 contributes to tumor immune surveillance remains unclear. The purposes of this study are to determine whether PAI-1 regulates the expression of immune checkpoint molecules to suppresses the immune response to cancer and demonstrate the potential of PAI-1 inhibition for cancer therapy.

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Since its discovery in 1965, our understanding of the hepatitis B virus (HBV) replication cycle and host immune responses has increased markedly. In contrast, our knowledge of the molecular biology of hepatitis delta virus (HDV), which is associated with more severe liver disease, is less well understood. Despite the progress made, critical gaps remain in our knowledge of HBV and HDV replication and the mechanisms underlying viral persistence and evasion of host immunity.

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[Molecular mechanism of DNA hypomethylating agents in myeloid tumors].

Rinsho Ketsueki

April 2024

Division of Molecular Oncology, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo.

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Sleep-disordered breathing is common among children with spinal muscular atrophy, but has been hardly studied among adult subjects. Little is known about sleep quality in spinal muscular atrophy. The aims of this study were to evaluate occurrence and characteristics of sleep-disordered breathing and subjective sleep quality among adolescent and adult patients with spinal muscular atrophy type 2 or 3.

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Background: Coronary heart disease is one of the leading causes of mortality worldwide. Secondary prevention is essential, as it reduces the risk of further coronary events. Mobile health (mHealth) technology could become a useful tool to improve lifestyles.

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Background: Coronary disease is the main cause of death around the world. mHealth technology is considered attractive and promising to promote behavioural changes aimed at healthy lifestyle habits among coronary patients. The purpose of this study is to evaluate the efficacy of an mHealth intervention regarding improved results in secondary prevention in patients after an acute myocardial infarction (AMI) or angina in terms of lifestyle, clinical variables and therapeutic compliance.

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Aim: This study compared neurodevelopmental screening questionnaires completed when preterm-born children reached 2 years of corrected age with social communication skills at 5.5 years of age.

Methods: Eligible subjects were born in 2011 at 24-34 weeks of gestation, participated in a French population-based epidemiological study and were free of motor and sensory impairment at 2 years of corrected age.

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Plasma membrane damage (PMD) occurs in all cell types due to environmental perturbation and cell-autonomous activities. However, cellular outcomes of PMD remain largely unknown except for recovery or death. In this study, using budding yeast and normal human fibroblasts, we found that cellular senescence-stable cell cycle arrest contributing to organismal aging-is the long-term outcome of PMD.

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Enterovirus A71 (EV-A71) infection involves a variety of receptors. Among them, two transmembrane protein receptors have been investigated in detail and shown to be critical for infection: P-selectin glycoprotein ligand-1 (PSGL-1) in lymphocytes (Jurkat cells), and scavenger receptor class B member 2 (SCARB2) in rhabdomyosarcoma (RD) cells. PSGL-1 and SCARB2 have been reported to be expressed on the surface of Jurkat and RD cells, respectively.

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Minor introns impact on hematopoietic malignancies.

Exp Hematol

April 2024

Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo, Japan. Electronic address:

In the intricate orchestration of the central dogma, pre-mRNA splicing plays a crucial role in the post-transcriptional process that transforms DNA into mature mRNA. Widely acknowledged as a pivotal RNA processing step, it significantly influences gene expression and alters the functionality of gene product proteins. Although U2-dependent spliceosomes efficiently manage the removal of over 99% of introns, a distinct subset of essential genes undergo splicing with a different intron type, denoted as minor introns, using U12-dependent spliceosomes.

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Objective: To report neurodevelopment at age 5.5 years according to developmental delay screening with the Ages & Stages Questionnaire (ASQ) in late infancy in preterm-born children.

Design: Population-based cohort study, EPIPAGE-2.

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Background: One of the key symptoms of Alzheimer's disease (AD) is the impairment of short-term memory. Hippocampal neurogenesis is essential for short-term memory and is known to decrease in patients with AD. Impaired short-term memory and impaired neurogenesis are observed in aged mice alongside changes in RNA expression of gap junction and metabolism-related genes in circulating leukocytes.

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Although antimicrobial peptides have been shown to inactivate viruses through disruption of their viral envelopes, clinical use of such peptides has been hampered by a number of factors, especially their enzymatically unstable structures. To overcome the shortcomings of antimicrobial peptides, peptoids (sequence-specific N-substituted glycine oligomers) mimicking antimicrobial peptides have been developed. We aimed to demonstrate the antiviral effects of antimicrobial peptoids against hepatitis B virus (HBV) in cell culture.

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BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state.

Nat Commun

December 2023

Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo, Japan.

Article Synopsis
  • ATP-dependent chromatin remodeling complexes, specifically non-canonical BAF (ncBAF), play important roles in hematopoietic stem cells (HSCs), but their functions haven't been fully explored.* -
  • The study focuses on BRD9, a key component of ncBAF, finding that its loss increases chromatin accessibility, leading to a preference for myeloid cell development while hindering B cell formation.* -
  • BRD9 is shown to interact with CTCF, which affects gene expression and chromatin structure in HSCs, highlighting ncBAF's crucial role in determining cell fate in both normal and cancerous blood cell development.*
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Importance: Recent evidence indicates the efficacy of β-amyloid immunotherapy for the treatment of Alzheimer disease, highlighting the need to promote β-amyloid removal from the brain. Cilostazol, a selective type 3 phosphodiesterase inhibitor, promotes such clearance by facilitating intramural periarterial drainage.

Objective: To determine the safety and efficacy of cilostazol in mild cognitive impairment.

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Nedd4-2 is an E3 ubiquitin ligase in which missense mutation is related to familial epilepsy, indicating its critical role in regulating neuronal network activity. However, Nedd4-2 substrates involved in neuronal network function have yet to be identified. Using mouse lines lacking Nedd4-1 and Nedd4-2, we identified astrocytic channel proteins inwardly rectifying K+ channel 4.

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[The role of SF3B1 mutations in EVI1-rearranged myeloid neoplasms].

Rinsho Ketsueki

November 2023

Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe.

In acute myeloid leukemia (AML), EVI1 rearrangement represented by inv(3)(q21q26) or t(3;3)(q21;q26) causes EVI1 overexpression via structural rearrangement of an enhancer, and confers poor prognosis. My colleagues and I performed a mutational analysis of EVI1-rearranged myeloid neoplasms and identified SF3B1, a core RNA splicing factor, as the most commonly co-mutated gene. Indeed, latent leukemia development in transgenic mice bearing the humanized inv(3)(q21q26) allele was significantly accelerated by co-occurrence of Sf3b1 mutation.

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