Publications by authors named "Takeshi Imamura"

RNA-dependent protein kinase (PKR) may have a positive regulatory role in controlling tumor growth and progression in hepatocellular carcinoma (HCC). However, the downstream substrates and the molecular mechanism of PKR in the growth and progression of HCC have not been clarified. In this study, mass spectrometry analysis was performed with immunoprecipitated samples, and 4.

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  • * Studies show that the loss of the Men1 protein in osteoblasts leads to structural bone changes similar to those observed in osteoporosis patients, characterized by decreased bone-forming and increased bone-resorbing activities.
  • * The research suggests that loss of Men1 triggers cellular senescence via mTORC1 activation and AMPK suppression, with potential treatment benefits from metformin, indicating a new avenue for therapeutic strategies against age-related osteoporosis.
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  • - The study focuses on how trehalose, a nonreducing disaccharide, impacts skin barrier function and addresses skin problems like atopic dermatitis (AD) by regulating skin-barrier-related genes in keratinocytes.
  • - It found that trehalose can counteract the negative effects of Th2 cytokines (IL-4/IL-13), which typically impair skin barrier function by downregulating important proteins and antimicrobial peptides.
  • - Trehalose achieves this by inhibiting IL-33 expression, activating Nrf2 for antioxidant defense, and preventing the activation of signaling pathways that worsen skin barrier dysfunction, suggesting its potential as a therapeutic agent for AD.
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Osteoporosis in postmenopausal women is one of the causes of femoral fractures and is prevented by the administration of bisphosphonates. Individual morphologies are considered to increase the risk of atypical fractures associated with long-term administration. To evaluate cortical bone morphology quantitatively, we established a method to measure the distance from the center point of a cross-section to the external and internal borders based on CT images.

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Targeting novel inhibitory ligands beyond anti-PD-1 and PD-L1 and CTLA-4 therapies is essential for the next decade of the immunotherapy era. Agents for the B7 family molecules B7-H3, B7-H4, and B7-H5 are emerging in clinical trial phases; therefore, further accumulation of evidence from both clinical and basic aspects is vital. Here, we applied a 7-color multiplexed imaging technique to analyze the profile of B7 family B7-H3/B7-H4/B7-H5 expression, in addition to PD-L1, and the spatial characteristics of immune cell infiltrates in urothelial carcinoma (UC).

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  • This study investigates the role of fatty acid-binding protein 4 (FABP4) in muscle insulin resistance, particularly focusing on its postprandial levels in individuals with type 2 diabetes compared to those without diabetes.
  • Results show that individuals with type 2 diabetes have higher postprandial FABP4 levels, which correlate with markers of muscle insulin resistance, indicating that elevated FABP4 may contribute to impaired glucose metabolism.
  • The research also demonstrates that FABP4 can influence glucose uptake in muscle cells, suggesting that it may inhibit insulin signaling, thereby playing a significant role in insulin resistance in type 2 diabetes.
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  • - Camurati-Engelmann disease (CED) is a genetic bone disorder categorized into two types based on TGFB1 mutations, where CED2 lacks these mutations.
  • - In this study, researchers discovered two new mutations in the TGFB2 gene in CED2 patients, which affect a specific region of the gene, potentially leading to increased TGF-β2 activity and bone formation.
  • - The findings indicate that CED2 may result from heightened TGF-β2 signaling due to a loss of regulatory functions of the latency-associated peptide (LAP), highlighting distinct roles of TGFB1 and TGFB2 in bone development.
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High-speed three-dimensional (3D) imaging is essential for revealing the structure and functions of biological specimens. Confocal laser scanning microscopy has been widely employed for this purpose. However, it requires a time-consuming image-stacking procedure.

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Background: Doxorubicin (Dox) is effective against different types of cancers, but it poses cardiotoxic side effects, frequently resulting in irreversible heart failure. However, the complexities surrounding this cardiotoxicity, especially at sublethal dosages, remain to be fully elucidated. We investigated early cellular disruptions in response to sublethal Dox, with a specific emphasis on the role of phosphorylated calcium/calmodulin-dependent protein kinase II (CaMKII) in initiating mitochondrial dysfunction.

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  • Sweat plays a crucial protective role for the body, and its dysfunction can lead to skin diseases like palmoplantar pustulosis (PPP), which is linked to decreased E-cadherin levels in skin lesions.
  • Research suggests that interleukin (IL)-1 in sweat may contribute to these changes, showing how inflammatory molecules affect skin health.
  • Advanced techniques, such as live imaging with a new fluorescent dye (JSAC) and the "LASER-snipe" method, allow scientists to study sweat-related processes and the onset of PPP in living tissues, providing insights for future research in skin disorders.
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Transforming growth factor β (TGF-β) is a multifunctional cytokine that induces a diverse set of cellular processes principally through Smad-dependent transcription. Transcriptional responses induced by Smads are tightly regulated by Smad cofactors and histone modifications; however, the underlying mechanisms have not yet been elucidated in detail. We herein report lysine methyltransferase SET8 as a negative regulator of TGF-β signaling.

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Background: Hepatic insulin clearance (HIC) is an important pathophysiology of type 2 diabetes mellitus (T2DM). HIC was reported to decrease in patients with type 2 diabetes and metabolic syndrome. HIC is originally calculated by post-load insulin and C-peptide from the oral glucose tolerance test (OGTT).

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Immunotherapy using bispecific antibodies including bispecific T-cell engager (BiTE) has the potential to enhance the efficacy of treatment for relapsed/refractory multiple myeloma. However, myeloma may still recur after treatment because of downregulation of a target antigen and/or myeloma cell heterogeneity. To strengthen immunotherapy for myeloma while overcoming its characteristics, we have newly developed a BiTE-based modality, referred to as bridging-BiTE (B-BiTE).

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Cardiovascular disease is a major cause of death worldwide, with high prevalence and morbidity. Recent advances in technology have reported that abnormalities in the gut microbiota are associated with a variety of diseases, including cardiovascular diseases. The gut microbiota is a complex ecosystem that plays an important role in maintaining host health.

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Two-photon excitation in light-sheet microscopy advances applications to live imaging of multicellular organisms. In a previous study, we developed a two-photon Bessel beam light-sheet microscope with a nearly 1-mm field of view and less than 4-μm axial resolution, using a low magnification (10×), middle numerical aperture (NA 0.5) detection objective.

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Neural tube defects (NTDs) cause fetal and pediatric deaths or lifelong neurological disabilities. No effective treatment is currently available for NTDs. We attempted to elucidate the pathogenesis of NTDs and propose a therapeutic strategy.

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Background: Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme involved in alcohol metabolism. ALDH2 polymorphism has been reported as a risk factor for type 2 diabetes mellitus (T2DM) and is associated with liver insulin resistance due to alcohol consumption in non-diabetic individuals. Herein, we investigated the association between ALDH2 polymorphisms and insulin resistance in patients with T2DM.

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Epstein-Barr virus (EBV) is a human herpes virus that latently infects B lymphocytes. When EBV is reactivated, host B cells differentiate into plasma cells and produce IgM-dominant antibodies as well as many progeny virions. The aims of the present study were to confirm the IgM dominance of thyrotropin-receptor antibodies (TRAbs) produced by EBV reactivation and investigate the roles of TRAb-IgM in Graves' disease.

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The cutting edge of cancer immunotherapy extends to ecto-5'-nucleotidase (CD73), a cell membrane enzyme that targets the metabolism of extracellular adenosine. We herein focused on the expression of CD73 to clarify the state of CD73 positivity in cancer immunity and tumor microenvironment, thereby revealing a new survival predictor for patients with bladder cancer (BCa). We used clinical tissue microarrays of human BCa and simultaneously performed the fluorescent staining of cell type-specific markers (CD3, CD8, Foxp3, programmed cell death protein 1, and programmed death-ligand 1 [PD-L1]) and CD73 together with DAPI for nuclear staining.

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Insulin-regulated glucose transport is dependent on glucose transporter GLUT4 translocation to the plasma membrane, which incorporates glucose into the cells, mainly in adipose tissue and skeletal muscle. Insulin receptor signaling can stimulate GLUT4 vesicle transport from perinuclear pool to the plasma membrane via the vesicle transport machinery. At first, insulin signaling is divided to the multiple pathways, such as Akt/PKB and PKC-zeta/lambda.

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Introduction: Pancreatic and duodenal homeobox factor-1 () is an imperative gene for insulin secretion in maturity-onset diabetes of the young 4. gene polymorphism was associated with lower first-phase insulin secretion in a genome-wide association study of intravenous glucose tolerance test. It was not associated with type 2 diabetes risk and insulin secretion in a genome-wide oral glucose tolerance test study.

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  • Trehalose, a disaccharide of glucose, enhances the spread of the epidermal layer in living skin equivalents (LSE) without adverse effects when applied to human fibroblasts.
  • RNA-seq analysis showed that trehalose treatment activates the CDKN1A pathway, impacting various factors related to cell behavior and growth.
  • Application of trehalose-treated fibroblasts in wound healing significantly improved closure and capillary formation in experimental mice, with the effects dependent on the CDKN1A pathway, suggesting potential therapeutic benefits for wound repair.
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For in vivo two-photon fluorescence microscopy (2PM) imaging, the development of techniques that can improve the observable depth and temporal resolution is an important challenge to address biological and biomedical concerns such as vascular dynamics in the deep brain (typically the hippocampal region) of living animals. Improvements have been achieved through two approaches: an optical approach using a highly tissue-penetrating excitation laser oscillating in the second near-infrared wavelength region (NIR-II, 1100-1350 nm) and a chemical approach employing fluorescent probes with high two-photon brightness (characterized by the product of the two-photon absorption cross section, σ, and the fluorescence quantum yield, Φ). To integrate these two approaches, we developed a fluorescent dye exhibiting a sufficiently high σΦ value of 68 Goeppert-Mayer units at 1100 nm.

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The planetary missions including the Venus Climate Orbiter 'Akatsuki' provide new information on various atmospheric phenomena. Nevertheless, it is difficult to elucidate their three-dimensional structures globally and continuously only from observations because satellite observations are considerably limited in time and space. We constructed the first 'objective analysis' of Venus' atmosphere by assimilating cloud-top horizontal winds on the dayside from the equator to mid-latitudes, which is frequently obtained from Akatsuki's Ultraviolet Imager (UVI).

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