A5011663100- Receptor Mechanisms and Signaling
- Cholesterol and Lipid Metabolism
- Biochemical Analysis and Sensing Techniques
- Diabetes Treatment and Management
- Protease and Inhibitor Mechanisms
- Neuropeptides and Animal Physiology
- Diet and metabolism studies
- RNA Research and Splicing
- Magnesium in Health and Disease
- MicroRNA in disease regulation
- Regulation of Appetite and Obesity
- Connective tissue disorders research
- Adipose Tissue and Metabolism
- Gut microbiota and health
- Blood Coagulation and Thrombosis Mechanisms
- Cancer-related molecular mechanisms research
- Crystallization and Solubility Studies
- Peroxisome Proliferator-Activated Receptors
- Inflammatory mediators and NSAID effects
- X-ray Diffraction in Crystallography
- Trace Elements in Health
- Pharmacology and Obesity Treatment
- Fatty Acid Research and Health
- Eicosanoids and Hypertension Pharmacology
- Ion Channels and Receptors
Kyoto Pharmaceutical University
2008-2023
Kyoto University
2012-2023
Japan Agency for Medical Research and Development
2019
Tokyo University of Agriculture and Technology
2019
Tohoku University
2012-2018
Keihin (Japan)
2016
Kindai University
2013
Northwestern University
2013
Sanford Burnham Prebys Medical Discovery Institute
2013
UCLouvain
2013
The maintenance of energy homeostasis is essential for life, and its dysregulation leads to a variety metabolic disorders. Under fed condition, mammals use glucose as the main fuel, short-chain fatty acids (SCFAs) produced by colonic bacterial fermentation dietary fiber also contribute significant proportion daily requirement. ketogenic conditions such starvation diabetes, ketone bodies in liver from are used sources. To balance intake, excess trigger an increase or decrease expenditure,...
Gut microbiota mediates the effects of diet, thereby modifying host metabolism and incidence metabolic disorders. Increased consumption omega-6 polyunsaturated fatty acid (PUFA) that is abundant in Western diet contributes to obesity related diseases. Although gut-microbiota-related pathways dietary PUFAs were recently elucidated, on physiological function remain unclear. Here, we demonstrate gut confers resistance high-fat (HFD)-induced by modulating metabolism. Supplementation...
Long-term inhibition of nitric oxide synthase by L-arginine analogues such as N(ω)-nitro-l-arginine methyl ester (L-NAME) has been shown to induce senescence in vitro and systemic hypertension arteriosclerosis vivo. We previously reported that plasminogen activator inhibitor-1 (PAI-1)-deficient mice (PAI-1(-/-)) are protected against L-NAME-induced pathologies. In this study, we investigated whether a novel, orally active PAI-1 antagonist (TM5441) similar protective effect L-NAME treatment....
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by inhibiting translation and/or inducing degradation of target mRNAs, and they play important roles in a wide variety biological functions including cell differentiation, tumorigenesis, apoptosis metabolism. However, there is paucity information concerning the regulatory mechanism miRNA expression. Here we report identification growth factor-regulated miRNAs using PC12 line, an established model neuronal...
Phorbol 12-myristate 13-acetate (PMA) induces megakaryocytic differentiation of the human chronic myelocytic leukemia cell line K562. We examined potential regulatory role microRNAs (miRNAs) in this process. Genome-wide expression profiling identified 21 miRNAs (miRs) that were induced by treatment K562 cells with PMA. Among them, miR-34a, miR-221, and miR-222 was early stages maintained throughout late differentiation. Cell signaling analysis showed activation extracellular signal-regulated...
Adhesive small bowel obstruction remains a common problem for surgeons. After surgery, platelet aggregation contributes to coagulation cascade and fibrin clot formation. With clotting, degradation is simultaneously enhanced, driven by tissue plasminogen activator-mediated cleavage of form plasmin. The aim this study was investigate the cellular events proteolytic responses that surround activator inhibitor (PAI-1; Serpine1) inhibition postoperative adhesion. Peritoneal adhesion induced gauze...
Plasminogen activator inhibitor (PAI)-1 is predictive of poor outcome in several types cancer. The present study investigated the biological role for PAI-1 ovarian cancer and potential targeted pharmacotherapeutics. In patients with cancer, mRNA expression tumor tissues was positively correlated prognosis. To determine cell proliferation effects inhibition were examined PAI-1-expressing cells. knockdown by small interfering RNA resulted significant suppression growth accompanied G2/M cycle...
Tric-b knockout mice serve as a model for studying the bone defects of osteogenesis imperfecta.
Abstract We report herein a nonbiomimetic strategy for the total synthesis of plicamine‐type alkaloids zephycarinatines C and D. The key feature is stereoselective reductive radical ipso ‐cyclization using visible‐light‐mediated photoredox catalysis. This cyclization enabled construction 6,6‐spirocyclic core structure through addition carbon‐centered onto aromatic ring. Biological evaluation their derivatives revealed that synthetic derivative with keto group displays moderate inhibitory...
Numerous studies have shown a paradoxical positive correlation between elevated levels of plasminogen activator inhibitior-1 (PAI-1) in tumors and blood cancer patients with poor clinical outcome, suggesting that PAI-1 could be therapeutic target. Here we tested two orally bioavailable small molecule inhibitors (TM5275 TM5441) for their efficacy pre-clinical models cancer. We demonstrated these decreased cell viability several human lines an IC50 the 9.7 to 60.3 μM range induced intrinsic...
Macrophage (Mϕ) migration rests on the adhesion/detachment between Mϕ surface components and extracellular matrixes, contribution of numerous inflammatory disorders. Plasminogen activator inhibitor (PAI)-1, a serine protease inhibitor, influences motility through an action distinct from its classical modulation plasmin-based fibrinolytic process. We rely here small molecule PAI-1 (TM5275) to investigate role in pathogenesis renal injury.Mϕ was inhibited both vitro vivo by TM5275. It also...
Multiple sclerosis (MS) is characterized by inflammatory demyelination and deposition of fibrinogen in the central nervous system (CNS). Elevated levels a critical inhibitor mammalian fibrinolitic system, plasminogen activator 1 (PAI-1) have been demonstrated human animal models MS. In experimental studies that resemble neuroinflammatory disease, PAI-1 deficient mice display preserved neurological structure function compared to wild type mice, suggesting link between fibrinolytic pathway We...