A5003243340- Cancer-related gene regulation
- RNA modifications and cancer
- Cancer, Lipids, and Metabolism
- Heme Oxygenase-1 and Carbon Monoxide
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Extracellular vesicles in disease
- Pharmacological Receptor Mechanisms and Effects
- Neonatal Health and Biochemistry
- Adrenal and Paraganglionic Tumors
- Galectins and Cancer Biology
- Signaling Pathways in Disease
- Ubiquitin and proteasome pathways
- Adipose Tissue and Metabolism
- Spectroscopy Techniques in Biomedical and Chemical Research
- Microtubule and mitosis dynamics
- Sulfur Compounds in Biology
- Hormonal Regulation and Hypertension
- Sesame and Sesamin Research
- Liver Disease Diagnosis and Treatment
- interferon and immune responses
- Alcohol Consumption and Health Effects
- Advanced Biosensing Techniques and Applications
- RNA Interference and Gene Delivery
- Mitochondrial Function and Pathology
Keio University
2015-2024
Kōchi University
2024
Japan Science and Technology Agency
2010-2023
Japan Agency for Medical Research and Development
2016-2020
Keio University Hospital
2016-2020
Osaka University
2013
Tokyo Institute of Technology
1999-2013
Nihon University
2013
National Center for Geriatrics and Gerontology
2013
Kyoto Prefectural University of Medicine
2013
Enhancement of cerebral blood flow by hypoxia is critical for brain function, but signaling systems underlying its regulation have been unclear. We report a pathway mediating hypoxia-induced vasodilation in studies monitoring vascular disposition cerebellar slices and intact mouse brains using two-photon intravital laser scanning microscopy. In this cascade, elicits via the coordinate actions H 2 S formed cystathionine β-synthase (CBS) CO generated heme oxygenase (HO)-2. Hypoxia diminishes...
Progesterone-receptor membrane component 1 (PGRMC1/Sigma-2 receptor) is a haem-containing protein that interacts with epidermal growth factor receptor (EGFR) and cytochromes P450 to regulate cancer proliferation chemoresistance; its structural basis remains unknown. Here crystallographic analyses of the PGRMC1 cytosolic domain at 1.95 Å resolution reveal it forms stable dimer through stacking interactions two protruding haem molecules. The iron five-coordinated by Tyr113, open surface...
iPSC-based drug discovery led to a phase 1/2a trial of ropinirole in ALS. 20 participants with sporadic ALS received or placebo for 24 weeks the double-blind period evaluate safety, tolerability, and therapeutic effects. Adverse events were similar both groups. During period, muscle strength daily activity maintained, but decline ALSFRS-R, which assesses functional status patients, was not different from that group. However, open-label extension group showed significant suppression ALSFRS-R...
APE1/Ref-1 is thought to be a multifunctional protein involved in reduction–oxidation (redox) regulation and base excision DNA repair, required for early embryonic development mice. has redox activity AP endonuclease activity, able enhance DNA-binding of several transcription factors, including NF-κB, AP-1 p53, through reduction their critical cysteine residues. However, it remains elusive exactly how carries out its essential functions vivo . Here, we show that not only reduces target...
Gold deposition with diagonal angle towards boehmite-based nanostructure creates random arrays of horse-bean-shaped nanostructures named gold-nanofève (GNF). GNF generates many electromagnetic hotspots as surface-enhanced Raman spectroscopy (SERS) excitation sources, and enables large-area visualization molecular vibration fingerprints metabolites in human cancer xenografts livers immunodeficient mice sufficient sensitivity uniformity. Differential screening GNF-SERS signals tumours those...
Abstract Triple-negative breast cancer (TNBC) chemoresistance hampers the ability to effectively treat patients. Identification of mechanisms driving can lead strategies improve treatment. Here, we revealed that protein arginine methyltransferase-1 (PRMT1) simultaneously methylates D-3-phosphoglycerate dehydrogenase (PHGDH), a critical enzyme in serine synthesis, and glycolytic enzymes PFKFB3 PKM2 TNBC cells. 13C metabolic flux analyses showed PRMT1-dependent methylation these three diverts...
Imaging MS combined with CE/MS serves as a method to provide semi-quantitative and spatial information of small molecular metabolites in tissue slices. However, not all including amino acids have fully been visualized, because low-ionization efficiency MALDI MS. This study aimed acquire for multiple frozen As derivatization reagent, p-N,N,N-trimethylammonioanilyl N'-hydroxysuccinimidyl carbamate iodide (TAHS) was applied increase their ionization detection sensitivity. Semi-quantitative...
Although circulating exosomes in blood play crucial roles cancer development and progression, difficulties quantifying hamper their application for reliable clinical testing. By combining the properties of nanobeads with optical disc technology, we have developed a novel device named ExoCounter to determine exact number sera patients various types cancer.In this system, individual were captured groove an coated antibodies against exosome surface antigens. The labeled antibody-conjugated...
Drug resistance is a major problem in the treatment of liver cancer. Mammalian Target Rapamycin 1 (mTORC1) inhibitors have been tested for cancer based on hyperactive mTOR this malignancy. However, their clinical trials showed poor outcome, most likely due to ability upregulate CD133 and promote chemoresistance. The + tumor–initiating stem cell–like cells (TICs) isolated from mouse human tumors are chemoresistant, identification an approach abrogate desired. In search compound that rescinds...
Hematopoietic stem cells (HSCs) maintain lifelong hematopoiesis by remaining quiescent in the bone marrow niche. Recapitulation of a state culture has not been achieved, as rapidly proliferate and differentiate vitro. After exhaustive analysis different environmental factor combinations concentrations way to mimic physiological conditions, we were able engraftable HSCs for 1 month under very low cytokine concentrations, hypoxia, high fatty acid levels. Exogenous acids required likely due...
Abstract The apurinic/apyrimidinic endonuclease 1/redox factor‐1 (Ape‐1/Ref‐1) is a multi‐functional protein, involved in DNA repair and the activation of redox‐sensitive transcription factors. Ape‐1/Ref‐1 redox domain acts as cytoprotective element normal endothelial cells, mitigating deleterious effects apoptotic stimuli through induction survival signals. We explored role maintenance tumor‐associated endothelium, progenitor cells (EPCs), which contribute to tumor angiogenesis. demonstrate...
Background. The immunohistochemical detection of aldosterone synthase (CYP11B2) and steroid 11β-hydroxylase (CYP11B1) has enabled the identification aldosterone-producing cell clusters (APCCs) in subcapsular portion human adult adrenal cortex. We hypothesized that adrenals have layered zonation early postnatal stages are remodeled to possess APCCs over time. Purposes. To investigate changes adrenocortical with age. Methods. retrospectively analyzed tissues prepared from 33 autopsied patients...
Short-chain fatty acids (SCFAs) produced by gastrointestinal microbiota regulate immune responses, but host molecular mechanisms remain unknown. Unbiased screening using SCFA-conjugated affinity nanobeads identified apoptosis-associated speck-like protein (ASC), an adaptor of inflammasome complex, as a noncanonical SCFA receptor besides GPRs. SCFAs promoted activation in macrophages binding to its ASC PYRIN domain. Activated suppressed survival Salmonella enterica serovar Typhimurium (S....
Abstract Recently, an international randomized controlled clinical trial showed that patients with SARS-CoV-2 infection treated orally the 3-chymotrypsin-like protease (3CL pro ) inhibitor PF-07321332 within three days of symptom onset 89% lower risk COVID-19-related hospital admission/ death from any cause as compared who received placebo. Lending support to this critically important result aforementioned trial, we demonstrated in our study infected a SARS-Cov-2 sub-lineage (B.1.1.284)...
Multiprotein bridging factor 1 (MBF1) is a coactivator which mediates transcriptional activation by interconnecting the general transcription TATA element-binding protein and gene-specific activators such as <i>Drosophila</i>nuclear receptor FTZ-F1 or yeast basic leucine zipper GCN4. The human homolog of MBF1 (hMBF1) has been identified but its function, especially in transcription, remains unclear. Here we report cDNA cloning functional analysis hMBF1. Two isoforms, term hMBF1α hMBF1β, have...
Osteoclast differentiation factor (ODF)/receptor activator of NF-kappaB ligand is essential for inducing the mature osteoclasts. We find that nuclear Y (NF-Y) binds to CCAAT box on ODF promoter and regulates its basal transcriptional activity. The gene required induction by vitamin D3, suggesting NF-Y coregulates this along with VDR. Chromatin immunoprecipitation analysis reveals recruitment RNA polymerase II (RNAPII) TATA binding protein promoter. Stimulation D3 facilitates VDR p300 onto...
Heterogeneous nuclear ribonucleoproteins (hnRNPs) are thought to be involved in pre‐mRNA processing. hnRNP‐U, also termed scaffold attachment factor A (SAF‐A), binds and matrix/scaffold region DNA elements. However, its role the regulation of gene expression is as yet poorly understood. In present study, we show that hnRNP‐U specifically enhances tumor necrosis α mRNA by increasing stability, possibly through binding 3′ untranslated region. We several other genes well, including GADD45A,...