Publications by authors named "Yusuke Higuchi"

Article Synopsis
  • - Choline is important for making essential molecules in the body, but how it enters mitochondria and its overall significance is not well understood.
  • - The study identifies SLC25A48, a previously unknown protein in the mitochondrial membrane, as vital for transporting choline into mitochondria and facilitating important metabolic processes.
  • - Loss of SLC25A48 disrupts choline import, leading to increased oxidative stress and potential issues with cell growth, highlighting its role in energy production and cell survival.
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Aims: Specific cavins and caveolins, known as caveola-related proteins, have been implicated in cardiac hypertrophy and myocardial injury. Cavin-2 forms complexes with other caveola-related proteins, but the role of Cavin-2 in cardiomyocytes (CMs) is poorly understood. Here, we investigated an unknown function of Cavin-2 in CMs.

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Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is a rare subtype of non-Hodgkin lymphoma (NHL) with poor prognosis, particularly in relapsed or refractory patients. Thus, timely detection of relapse and appropriate disease management are crucial. We present two patients with ENKTL, wherein positron emission tomography-computed tomography (PET-CT) with total-body coverage after induction therapy, detected newly relapsed regions in the bone marrow of the lower leg prior to progression.

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Caveolin-1 (CAV1) and Cavin-1 are components of caveolae, both of which interact with and influence the composition and stabilization of caveolae. CAV1 is associated with pulmonary arterial hypertension (PAH). Bone morphogenetic protein (BMP) type 2 receptor (BMPR2) is localized in caveolae associated with CAV1 and is commonly mutated in PAH.

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Background: Infectious aortic disease is a rare and fatal disease, that requires the appropriate intervention. An accurate diagnosis should be promptly established. However, this is difficult because the clinical manifestations of this disease vary and are non-specific.

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Aims: Transforming growth factor β (TGF-β) signalling is one of the critical pathways in fibroblast activation, and several drugs targeting the TGF-β/Smad signalling pathway in heart failure with cardiac fibrosis are being tested in clinical trials. Some caveolins and cavins, which are components of caveolae on the plasma membrane, are known for their association with the regulation of TGF-β signalling. Cavin-2 is particularly abundant in fibroblasts; however, the detailed association between Cavin-2 and cardiac fibrosis is still unclear.

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Background: Optimal cefepime dosing is a challenge because of its dose-dependent neurotoxicity. This study aimed to determine individualized cefepime dosing for febrile neutropenia in patients with lymphoma or multiple myeloma.

Methods: This prospective study enrolled 16 patients receiving cefepime at a dose of 2 g every 12 hours.

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A 65-year-old woman was referred to the hospital for further investigation of weight loss, hyperproteinemia, and anemia. Serum immunofixation electrophoresis revealed IgM-κ M protein. Bone marrow examination revealed an increase in the number of B -cells with immunoglobulin kappa light-chain restriction.

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Article Synopsis
  • The Omicron variant of SARS-CoV-2 evolves to evade immunity from vaccines and prior infections, leading to the emergence of subvariants that escape current antibody treatments.
  • An engineered ACE2 decoy shows effectiveness in neutralizing various Omicron subvariants and does not lead to the development of viral escape mutants.
  • Inhalation of aerosolized ACE2 decoys has proven beneficial in rodent models and macaques, suggesting this method could enhance COVID-19 treatment efficacy without invasive procedures.
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Introduction: Our previous work has demonstrated significant effects on the oxidative stress response, mitochondrial function, and oxidative phosphorylation in the livers and intestines of p300 S89A knockin (S89AKI) mice. We now show that this mutation is also associated with brain metabolic defects and neuronal differentiation.

Methods: p300 S89A edited P19 cells, and S89AKI mice demonstrated metabolic and neuronal differentiation defects based on proteomic, cell biological and PET imaging studies.

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Article Synopsis
  • SARS-CoV-2 Omicron subvariants have developed the ability to evade detection by certain antibodies that target their receptor-binding sites (RBS).
  • Researchers identified a key area, Y489, that is vulnerable to broadly neutralizing antibodies and revealed how multiple antibodies interact with both Y489 and F486, linking this to the emergence of resistant subvariants.
  • A newly designed antibody (NIV-10/FD03) effectively neutralized the XBB variant and shows promise for developing therapies resistant to viral evolution and escape mechanisms.
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Article Synopsis
  • * Traditional treatments aimed at reducing fat in the liver have been ineffective, as they can worsen liver inflammation by releasing toxic fatty acids.
  • * Researchers developed a new method using a synthetic protein to enhance "lipophagy," a process that helps remove fat from liver cells, showing promising results in mouse models and identifying existing drugs, alpelisib and digoxin, that can activate this process to prevent NASH progression.
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Pulmonary hypertension (PH) is associated with a poor prognosis even in recent years. Caveolin-1 (CAV1), a caveolae-associated protein, is a causal gene in PH. Cavin-2, one of the other caveolae-associated proteins, forms protein complexes with CAV1 and influences each other's functions.

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Background And Objective: The first clinically evaluated CBP/β-catenin antagonist, PRI-724, displayed an excellent safety profile administered intravenously via continuous infusion. Eisai recently disclosed a third-generation, orally available, reportedly CBP/β-catenin antagonist, E7386. However, several structural features and the reported cytotoxicity of E7386 were unexpected for a specific CBP/β-catenin antagonist.

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The natural product family of the fusicoccanes (FCs) has been shown to display anti-cancer activity, especially when combined with established therapeutic agents. FCs stabilize 14-3-3 protein-protein interactions (PPIs). Here, we tested combinations of a small library of FCs with interferon α (IFNα) on different cancer cell lines and report a proteomics approach to identify the specific 14-3-3 PPIs that are induced by IFNα and stabilized by FCs in OVCAR-3 cells.

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The major concern with COVID-19 therapeutic monoclonal antibodies is the loss of efficacy against continuously emerging variants of SARS-CoV-2. To predict antibody efficacy against future Omicron subvariants, we conducted deep mutational scanning (DMS) encompassing all single mutations of the receptor-binding domain of the BA.2 strain utilizing an inverted infection assay with an ACE2-harboring virus and library spike-expressing cells.

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Human hepatocyte culture system represents by far the most physiologically relevant model for our understanding of liver biology and diseases; however, its versatility has been limited due to the rapid and progressive loss of genuine characteristics, indicating the inadequacy of in vitro milieu for fate maintenance. This study, therefore, is designed to define environmental requirements necessary to sustain the homeostasis of terminally differentiated hepatocytes. Our study reveals that the supplementation of dimethyl sulfoxide (DMSO) is indispensable in mitigating fate deterioration and promoting adaptation to the in vitro environment, resulting in the restoration of tight cell-cell contact, cellular architecture, and polarity.

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Follicular T-cell lymphoma (FTCL) is a rare disease, recently defined in the revised WHO classification Tumours of Haematopoietic and lymphoid tissues (4th edition). Although angioimmunoblastic T-cell lymphoma (AITL) and FTCL share similar T follicular helper (TFH) cell immunophenotypes and gene mutations, the clinical course of FTCL is not well characterized. Herein, we report the case of a 91-year-old woman with FTCL, who was successfully treated with corticosteroid.

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There remains an unmet clinical need to identify which patients with diffuse large B-cell lymphoma (DLBCL) would benefit from central nervous system (CNS) prophylaxis, due to the low positive predictive value (PPV; 10%-15%) of the currently available predictive models. To stratify patients at high risk of developing CNS relapse, we retrospectively analyzed 182 patients with DLBCL initially treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), or a R-CHOP-like regimen. Among them, 17 patients relapsed with CNS involvement, and the 2-year rate of CNS relapse was 7.

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Chemotherapy in combination with mogamulizumab (Mog) was approved in Japan in 2014 for untreated aggressive adult T-cell leukaemia-lymphoma (ATL), but the survival benefit remains unclear. Therefore, we retrospectively analysed clinical outcomes in 39 transplant-ineligible patients with untreated aggressive ATL at Kumamoto University Hospital between 2010 and 2021. The probability of four-year overall survival was 46.

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