Takashi Dan
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View article: Experimental Study on the Treatment of Ulcerative Proctitis in Rats by Combining Baitouweng Decoction with Mesalamine Retention Enema
Experimental Study on the Treatment of Ulcerative Proctitis in Rats by Combining Baitouweng Decoction with Mesalamine Retention Enema Open
To study the effect and mechanism of Baitouweng decoction, mesalamine and its combination with an enema in the treatment of ulcerative proctitis in rats is the objective of the study. The rats were divided into seven groups: Control (Norma…
View article: Deep molecular response in patients with chronic phase chronic myeloid leukemia treated with the plasminogen activator inhibitor‐1 inhibitor <scp>TM5614</scp> combined with a tyrosine kinase inhibitor
Deep molecular response in patients with chronic phase chronic myeloid leukemia treated with the plasminogen activator inhibitor‐1 inhibitor <span>TM5614</span> combined with a tyrosine kinase inhibitor Open
Background We recently showed that pharmacological inhibition of plasminogen activator inhibitor‐1 (PAI‐1) activity, based on TM5614, increases cell motility and induces the detachment of hematopoietic stem cells from their niches. In this…
View article: Molecular mechanism of schizophrenia-like behavioral deficits induced by methylglyoxal detoxification impairments
Molecular mechanism of schizophrenia-like behavioral deficits induced by methylglyoxal detoxification impairments Open
Methylglyoxal (MG) is a reactive and cytotoxic alpha-dicarbonyl product of glycolysis. Various detoxification systems work together in vivo to remove highly toxic MGs, including a glyoxalase system by Glyoxalase 1 (GLO1) and GLO2, and the …
View article: High-sucrose diets contribute to brain angiopathy with impaired glucose uptake and psychosis-related higher brain dysfunctions in mice
High-sucrose diets contribute to brain angiopathy with impaired glucose uptake and psychosis-related higher brain dysfunctions in mice Open
High-sugar diet in adolescence induces neural angiopathy and multiple psychiatric endophenotypes with impaired glucose logistics.
View article: Combined glyoxalase 1 dysfunction and vitamin B6 deficiency in a schizophrenia model system causes mitochondrial dysfunction in the prefrontal cortex
Combined glyoxalase 1 dysfunction and vitamin B6 deficiency in a schizophrenia model system causes mitochondrial dysfunction in the prefrontal cortex Open
View article: Accumulation of Carbonyl Proteins in the Brain of Mouse Model for Methylglyoxal Detoxification Deficits
Accumulation of Carbonyl Proteins in the Brain of Mouse Model for Methylglyoxal Detoxification Deficits Open
Recent studies have shown that carbonyl stress is a causative factor of schizophrenia, categorized as carbonyl stress-related schizophrenia (CS-SCZ). However, the correlation between carbonyl stress and the pathogenesis of this disease is …
View article: Impairment of methylglyoxal detoxification systems causes mitochondrial dysfunction and schizophrenia-like behavioral deficits
Impairment of methylglyoxal detoxification systems causes mitochondrial dysfunction and schizophrenia-like behavioral deficits Open
Methylglyoxal (MG) is a cytotoxic α -dicarbonyl byproduct of glycolysis. Our bodies have several bio-defense systems to detoxify MG, including an enzymatic system by glyoxalase (GLO) 1 and a scavenge system by vitamin B6 (VB6). We know a p…
View article: Inhibition of Plasminogen Activator Inhibitor-1 Activation Suppresses High Fat Diet-Induced Weight Gain via Alleviation of Hypothalamic Leptin Resistance
Inhibition of Plasminogen Activator Inhibitor-1 Activation Suppresses High Fat Diet-Induced Weight Gain via Alleviation of Hypothalamic Leptin Resistance Open
Leptin resistance is an important mechanism underlying the development and maintenance of obesity and is thus regarded as a promising target of obesity treatment. Plasminogen activator inhibitor 1 (PAI-1), a physiological inhibitor of tiss…
View article: High Sucrose Diets Contribute to Brain Angiopathy with Impaired Glucose Uptake, and Psychosis-related Higher Brain Dysfunctions in Mice
High Sucrose Diets Contribute to Brain Angiopathy with Impaired Glucose Uptake, and Psychosis-related Higher Brain Dysfunctions in Mice Open
Metabolic dysfunction is thought to contribute to the severity of psychiatric disorders; however, it has been unclear whether current high-simple-sugar diets contribute to pathogenesis of these diseases. Here we demonstrate that a high-suc…
View article: Furan- and Thiophene-2-Carbonyl Amino Acid Derivatives Activate Hypoxia-Inducible Factor via Inhibition of Factor Inhibiting Hypoxia-Inducible Factor-1
Furan- and Thiophene-2-Carbonyl Amino Acid Derivatives Activate Hypoxia-Inducible Factor via Inhibition of Factor Inhibiting Hypoxia-Inducible Factor-1 Open
Induction of a series of anti-hypoxic proteins protects cells during exposure to hypoxic conditions. Hypoxia-inducible factor-α (HIF-α) is a major transcription factor that orchestrates this protective effect. To activate HIF exogenously, …
View article: Identification of novel plasminogen activator inhibitor-1 inhibitors with improved oral bioavailability: Structure optimization of N-acylanthranilic acid derivatives
Identification of novel plasminogen activator inhibitor-1 inhibitors with improved oral bioavailability: Structure optimization of N-acylanthranilic acid derivatives Open
View article: New direction of PAI-1 inhibitor development: Clinical application to cancer treatment
New direction of PAI-1 inhibitor development: Clinical application to cancer treatment Open
要約：PAI-1 に直接作用する低分子阻害剤は，当初，血栓性疾患への適応に向けて研究開発が進められたが，PAI-1 阻害剤をツールとした研究等から，がんや糖尿病，肥満などのメタボリックシンドローム，さらには，多発性硬化症やアルツハイマー病などの神経疾患への適応の可能性が示唆されている．一方で，PAI-1 阻害剤の開発研究は世界的になされてきたが，現在までに，その臨床試験の報告は，PAI-749（diaplasinin，Wyeth Research 社）の第I相試験成績に留ま…
View article: Pyridoxamine: A novel treatment for schizophrenia with enhanced carbonyl stress
Pyridoxamine: A novel treatment for schizophrenia with enhanced carbonyl stress Open
Aim The aim of this clinical trial was to obtain proof of concept for high‐dose pyridoxamine as a novel treatment for schizophrenia with enhanced carbonyl stress. Methods Ten Japanese schizophrenia patients with high plasma pentosidine, wh…
View article: TGF-β–induced intracellular PAI-1 is responsible for retaining hematopoietic stem cells in the niche
TGF-β–induced intracellular PAI-1 is responsible for retaining hematopoietic stem cells in the niche Open
Key Points TGF-β–induced intracellular PAI-1 regulates the balance of HSPCs localization between BM and periphery. Intracellular PAI-1 inhibits Furin-dependent maturation of MT1-MMP in HSPCs, resulting in the suppression of HSPC motility.
View article: Activation of the hypoxia‐inducible factor pathway induced by prolyl hydroxylase domain 2 deficiency enhances the effect of running training in mice
Activation of the hypoxia‐inducible factor pathway induced by prolyl hydroxylase domain 2 deficiency enhances the effect of running training in mice Open
Aims Hypoxic response mediated by hypoxia‐inducible factor ( HIF ) seems to contribute to the benefit of endurance training. To verify the direct contribution of HIF activation to running training without exposure to atmospheric hypoxia, w…
View article: Prolyl hydroxylase domain 2 deficiency promotes skeletal muscle fiber-type transition via a calcineurin/NFATc1-dependent pathway
Prolyl hydroxylase domain 2 deficiency promotes skeletal muscle fiber-type transition via a calcineurin/NFATc1-dependent pathway Open
View article: Erythropoietin Synthesis in Renal Myofibroblasts Is Restored by Activation of Hypoxia Signaling
Erythropoietin Synthesis in Renal Myofibroblasts Is Restored by Activation of Hypoxia Signaling Open
Erythropoietin (Epo) is produced by renal Epo-producing cells (REPs) in a hypoxia-inducible manner. The conversion of REPs into myofibroblasts and coincident loss of Epo-producing ability are the major cause of renal fibrosis and anemia. H…
View article: Hypoxia Signaling Cascade for Erythropoietin Production in Hepatocytes
Hypoxia Signaling Cascade for Erythropoietin Production in Hepatocytes Open
Erythropoietin (Epo) is produced in the kidney and liver in a hypoxia-inducible manner via the activation of hypoxia-inducible transcription factors (HIFs) to maintain oxygen homeostasis. Accelerating Epo production in hepatocytes is one p…
View article: Plasminogen Activator Inhibitor-1 Antagonist TM5484 Attenuates Demyelination and Axonal Degeneration in a Mice Model of Multiple Sclerosis
Plasminogen Activator Inhibitor-1 Antagonist TM5484 Attenuates Demyelination and Axonal Degeneration in a Mice Model of Multiple Sclerosis Open
Multiple sclerosis (MS) is characterized by inflammatory demyelination and deposition of fibrinogen in the central nervous system (CNS). Elevated levels of a critical inhibitor of the mammalian fibrinolitic system, plasminogen activator in…
View article: Inhibition of plasminogen activator inhibitor-1 is a potential therapeutic strategy in ovarian cancer
Inhibition of plasminogen activator inhibitor-1 is a potential therapeutic strategy in ovarian cancer Open
Plasminogen activator inhibitor (PAI)-1 is predictive of poor outcome in several types of cancer. The present study investigated the biological role for PAI-1 in ovarian cancer and potential of targeted pharmacotherapeutics. In patients wi…
View article: Podocyte injury-driven intracapillary plasminogen activator inhibitor type 1 accelerates podocyte loss via uPAR-mediated β<sub>1</sub>-integrin endocytosis
Podocyte injury-driven intracapillary plasminogen activator inhibitor type 1 accelerates podocyte loss via uPAR-mediated β<sub>1</sub>-integrin endocytosis Open
Podocyte-endothelial cell cross-talk is paramount for maintaining the filtration barrier. The present study investigated the endothelial response to podocyte injury and its subsequent role in glomerulosclerosis using the podocyte-specific …
View article: Hypoxia-Sensitive Reporter System for High-Throughput Screening
Hypoxia-Sensitive Reporter System for High-Throughput Screening Open
The induction of anti-hypoxic stress enzymes and proteins has the potential to be a potent therapeutic strategy to prevent the progression of ischemic heart, kidney or brain diseases. To realize this idea, small chemical compounds, which m…