A5103054778- Cholesterol and Lipid Metabolism
- Drug Transport and Resistance Mechanisms
- Liver Disease Diagnosis and Treatment
- Peroxisome Proliferator-Activated Receptors
- Metabolism and Genetic Disorders
- Pediatric Hepatobiliary Diseases and Treatments
- Liver Diseases and Immunity
- Diet and metabolism studies
- Corneal surgery and disorders
- Aldose Reductase and Taurine
- Cancer, Lipids, and Metabolism
- Gallbladder and Bile Duct Disorders
- Gut microbiota and health
- Muscle metabolism and nutrition
- Steroid Chemistry and Biochemistry
- Hormonal and reproductive studies
- Liver Disease and Transplantation
- Receptor Mechanisms and Signaling
- Immunodeficiency and Autoimmune Disorders
- Gastrointestinal disorders and treatments
- Biliary and Gastrointestinal Fistulas
- Chronic Lymphocytic Leukemia Research
- Lipid metabolism and biosynthesis
- Neurological and metabolic disorders
- Magnetic confinement fusion research
The University of Tokyo
2022-2025
Tokyo Medical University Ibaraki Medical Center
2015-2024
Kindai University
2015-2024
University of Tokyo Hospital
2022-2023
Tokyo Medical University
2006-2022
Bunkyo University
2021
Japan Atomic Energy Agency
1997-2020
Fukuoka University
2006-2018
University of Tsukuba
1997-2016
Juntendo University
2014-2016
The bile acid (BA) composition in mice is substantially different from that humans. Chenodeoxycholic (CDCA) an end product the human liver; however, mouse Cyp2c70 metabolizes CDCA to hydrophilic muricholic acids (MCAs). Moreover, humans, gut microbiota converts primary BAs, cholic and CDCA, into deoxycholic (DCA) lithocholic (LCA), respectively. In contrast, Cyp2a12 reverts this action these secondary BAs BAs. Here, we generated KO, Cyp2a12/Cyp2c70 double KO (DKO) using CRISPR-Cas9 system...
To investigate the dynamics of guanosine 3′,5′-cyclic monophosphate (cGMP) in single living cells, we constructed genetically encoded, fluorescent cGMP indicators by bracketing cGMP-dependent protein kinase (cGPK), minus residues 1–77, between cyan and yellow mutants green protein. decreased fluorescence resonance energy transfer (FRET) increased ratio to emissions up 1.5-fold with apparent dissociation constants ≈2 μM >100:1 selectivity for over cAMP. eliminate constitutive activity, Thr...
ARNO is a soluble guanine nucleotide exchange factor (GEF) for the Arf family of GTPases. Although in biochemical assays prefers Arf1 over Arf6 as substrate, its localization cells at plasma membrane (PM) suggests an interaction with Arf6. In this study, we found that activated HeLa and COS-7 resulting recruitment on to dynamic PM ruffles. By contrast, was less by than EFA6, canonical GEF. Remarkably, GTP-bound form recruited two proteins could be immunoprecipitated. binding not mediated...
We describe a highly sensitive and specific method for the quantification of key regulatory oxysterols in biological samples. This is based upon stable isotope dilution technique by liquid chromatography-tandem mass spectrometry (LC-MS/MS). After alkaline hydrolysis human serum (5 μl) or rat liver microsomes (1 mg protein), were extracted, derivatized into picolinyl esters, analyzed LC-MS/MS using electrospray ionization mode. The detection limits esters 4β-hydroxycholesterol,...
Bezafibrate is a widely used hypolipidemic agent and known as ligand of the peroxisome proliferator-activated receptors (PPARs). Recently this has come to be recognized potential anticholestatic medicine for treatment primary biliary cirrhosis (PBC) that does not respond sufficiently ursodeoxycholic acid (UDCA) monotherapy. The aim study was explore mechanisms bezafibrate by analyzing serum lipid biomarkers in PBC patients cell-based enzymatic gene expression assays. Nineteen with...
We have developed a highly sensitive and specific method for the analysis of serum sterol profiles. Sterols in 1 mul dried were derivatized into picolinyl esters (3beta-picolinate) analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using electrospray ionization (ESI) mode. In addition to cholesterol, 19 cholesterol precursors, cholestanol, campesterol, sitosterol, sitostanol identified simultaneously. Quantitative analyses 11 available sterols performed, detection limits...
Gut microbiota have profound effects on bile acid metabolism by promoting deconjugation, dehydrogenation, and dehydroxylation of primary acids in the distal small intestine colon. High-fat diet-induced dysbiosis gut dysregulation may be involved pathology steatosis patients with non-alcoholic fatty liver disease. Epigallocatechin-3-gallate (EGCG), most abundant polyphenolic catechin green tea, has been widely investigated for its inhibitory or preventive against liver. The aim present study...
In Japan, bezafibrate (BF) is a second-line agent for primary biliary cholangitis (PBC) that refractory to ursodeoxycholic acid (UDCA) treatment. From retrospective cohort (n = 873) from the Japan PBC Study Group, we enrolled 118 patients who had received UDCA monotherapy at least 1 year followed by combination therapy with UDCA+BF year. GLOBE and UK-PBC scores after (i.e., immediately before therapy) were compared those of therapy. The real outcomes estimated Kaplan-Meier analysis predicted...
Cholestenoic acids are formed as intermediates in metabolism of cholesterol to bile acids, and the biosynthetic enzymes that generate cholestenoic expressed mammalian CNS. Here, we evaluated acid profile cerebrospinal fluid (CSF) determined specific activate liver X receptors (LXRs), enhance islet-1 expression zebrafish, increase number oculomotor neurons developing mouse vitro vivo. While 3β,7α-dihydroxycholest-5-en-26-oic (3β,7α-diHCA) promoted motor neuron survival an LXR-dependent...
High-fat diet (HFD)-induced alteration in the gut microbial composition, known as dysbiosis, is increasingly recognized a major risk factor for various diseases, including colon cancer. This report describes comprehensive investigation of effect agaro-oligosaccharides (AGO) on HFD-induced alterations short-chain fatty acid contents and bile metabolism mice. C57BL/6N mice were fed control or HFD, with without AGO. Terminal restriction fragment-length polymorphism (T-RFLP) analysis produced...
CD19 chimeric antigen receptor (CAR) T-cell therapy is associated with potentially life-threatening immunological toxicities. We herein report an 81-year-old woman who experienced multiple perforations in the small intestine 8 days after tisagenlecleucel infusion for relapsed and refractory follicular lymphoma no gastrointestinal involvement. A pathological examination of resected revealed ulcers that formed resection but without Based on these findings, tocilizumab used cytokine release...
We investigated the enzyme defect in late cholesterol biosynthesis Smith-Lemli-Opitz syndrome, a recessively inherited developmental disorder characterized by facial dysmorphism, mental retardation, and multiple organ congenital anomalies. Reduced plasma tissue with increased 7-dehydrocholesterol concentrations are biochemical features diagnostic of defect. Using isotope incorporation assays, we measured transformation precursors, [3 alpha- 3H]lathosterol [1,2-3H]7-dehydrocholesterol into...
We investigated the inhibitory role of nitric oxide (NO)–cGMP–protein kinase G (PKG) pathway on receptor‐activated TRPC6 channels in both a heterologous expression system (HEK293 cells) and A7r5 vascular myocytes. Cationic currents due to were strongly suppressed (by ∼70%) by NO donor SNAP (100 μ m ) whether it was applied prior muscarinic receptor stimulation with carbachol (CCh; 100 or after G‐protein activation intracellular perfusion GTPγS ). A similar extent suppression also observed...
To date, many studies have been conducted using 25-hydroxycholesterol, which is a potent regulator of lipid metabolism. However, the origins this oxysterol not entirely elucidated. Cholesterol 25-hydroxylase one enzymes responsible for metabolism but expression enzyme very low in humans. This also synthesized by sterol 27-hydroxylase (CYP27A1) and cholesterol 24-hydroxylase(CYP46A1), it only minor product these enzymes. We now report that CYP3A synthesizes significant amount...
This paper reports the piezoelectric properties of ScAlN thin films. We evaluated coefficients d <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">33</sub> and xmlns:xlink="http://www.w3.org/1999/xlink">31</sub> Sc xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> Al xmlns:xlink="http://www.w3.org/1999/xlink">1-x</sub> N films directly deposited onto silicon wafers, as well radio frequency (RF) electrical characteristics...
Partially hydrolyzed guar gum (PHGG) is a water-soluble dietary fiber and used in solid liquid food to regulate gut function. The aim of this study was investigate effects PHGG on bowel movements (stool form frequency), plasma bile acids, quality life, microbiota healthy volunteers with tendency toward diarrhea, i.e., irritable syndrome diarrhea (IBS-D)-like symptoms. A randomized, double-blind, placebo-controlled, parallel trial performed 44 (22 males, 22 females, 41.9 ± 6.3 years old...