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81.
Swarnalakshmi Raman Arief Waskitho Resmi Raju Takuma Iwasa Daisuke Ikutame Kazuo Okura Masamitsu Oshima Yoshizo Matsuka 《International journal of molecular sciences》2022,23(11)
Trigeminal neuralgia is unilateral, lancinating, episodic pain that can be provoked by routine activities. Anticonvulsants, such as carbamazepine, are the drugs of choice; however, these possess side-effects. Microvascular decompression is the most effective surgical technique with a higher success rate, although occasionally causes adverse effects. The potential treatment for this type of pain remains unmet. Increased tetrahydrobiopterin (BH4) levels have been reported in association with axonal injury. This study aimed to evaluate the effect of tranilast on relieving neuropathic pain in animal models and analyze the changes in BH4 synthesis. Neuropathic pain was induced via infraorbital nerve constriction. Tranilast, carbamazepine, or saline was injected intraperitoneally to assess the rat’s post-intervention pain response. In the von Frey’s test, the tranilast and carbamazepine groups showed significant changes in the head withdrawal threshold in the ipsilateral whisker pad area. The motor coordination test showed no changes in the tranilast group, whereas the carbamazepine group showed decreased performance, indicating impaired motor coordination. Trigeminal ganglion tissues were used for the PCR array analysis of genes that regulate the BH4 pathway. Downregulation of the sepiapterin reductase (Spr) and aldoketo reductase (Akr) genes after tranilast injection was observed compared to the pain model. These findings suggest that tranilast effectively treats neuropathic pain. 相似文献
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Akihiro Honda Shotaro Kamata Makoto Akahane Yui Machida Kie Uchii Yui Shiiyama Yuki Habu Saeka Miyawaki Chihiro Kaneko Takuji Oyama Isao Ishii 《International journal of molecular sciences》2022,23(9)
Among the agonists against three peroxisome proliferator-activated receptor (PPAR) subtypes, those against PPARα (fibrates) and PPARγ (glitazones) are currently used to treat dyslipidemia and type 2 diabetes, respectively, whereas PPARδ agonists are expected to be the next-generation metabolic disease drug. In addition, some dual/pan PPAR agonists are currently being investigated via clinical trials as one of the first curative drugs against nonalcoholic fatty liver disease (NAFLD). Because PPARα/δ/γ share considerable amino acid identity and three-dimensional structures, especially in ligand-binding domains (LBDs), clinically approved fibrates, such as bezafibrate, fenofibric acid, and pemafibrate, could also act on PPARδ/γ when used as anti-NAFLD drugs. Therefore, this study examined their PPARα/δ/γ selectivity using three independent assays—a dual luciferase-based GAL4 transactivation assay for COS-7 cells, time-resolved fluorescence resonance energy transfer-based coactivator recruitment assay, and circular dichroism spectroscopy-based thermostability assay. Although the efficacy and efficiency highly varied between agonists, assay types, and PPAR subtypes, the three fibrates, except fenofibric acid that did not affect PPARδ-mediated transactivation and coactivator recruitment, activated all PPAR subtypes in those assays. Furthermore, we aimed to obtain cocrystal structures of PPARδ/γ-LBD and the three fibrates via X-ray diffraction and versatile crystallization methods, which we recently used to obtain 34 structures of PPARα-LBD cocrystallized with 17 ligands, including the fibrates. We herein reveal five novel high-resolution structures of PPARδ/γ–bezafibrate, PPARγ–fenofibric acid, and PPARδ/γ–pemafibrate, thereby providing the molecular basis for their application beyond dyslipidemia treatment. 相似文献
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Julie K. Furmick Dr. Ichiro Kaneko Angela N. Walsh Joanna Yang Jaskaran S. Bhogal Geoffrey M. Gray Juan C. Baso Drew O. Browder Jessica L. S. Prentice Luis A. Montano Chanh C. Huynh Lisa M. Marcus Dorian G. Tsosie Jungeun S. Kwon Alexis Quezada Nicole M. Reyes Brittney Lemming Puneet Saini Dr. Arjan van der Vaart Dr. Thomas L. Groy Dr. Pamela A. Marshall Dr. Peter W. Jurutka Dr. Carl E. Wagner 《ChemMedChem》2012,7(9):1551-1566
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Kazuo Nakajima Satoshi Ono Ryota Murai Yuzuru Kaneko 《Journal of Electronic Materials》2016,45(6):2837-2846
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Towards the improvement of thermal efficiency in lignite‐fired power generation: Concerning the utilization of Polish lignite deposits in state‐of‐the‐art IGCC technology
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Yosuke Komatsu Anna Sciazko Marcin Zakrzewski Taro Akiyama Akira Hashimoto Naoki Shikazono Shozo Kaneko Shinji Kimijima Janusz S. Szmyd Yoshinori Kobayashi 《国际能源研究杂志》2016,40(13):1757-1772
Integrated coal Gasification Combined Cycle (IGCC) is the most advanced technology for coal‐fired power generation. The two‐stage entrained flow gasification process allows for the use of a wide range of coal, as long as the gasification temperature is above the ash melting point of a used fuel. In this gasification technology, lignite, which often has a low ash melting point, can be preferably utilized. However, ash fluidity is also another importance, because the behaviour of molten slag can diminish a stable ash discharge from a gasifier. As the eligibility of coal ash properties is a considerable factor, water physically and chemically kept in lignite (30 – 60% in mass) attributes to deteriorating gasification efficiency, because it causes significant heat loss and increasing oxygen consumption. Developing a thermal evaporative lignite drying method will be a necessary attempt to apply lignite to the coal gasification process. For those preceded objectives, coal and ash properties and drying characteristics of several grades of Polish lignite, extracted from Belchatow and Turow deposits, have been experimentally investigated in a preliminary study evaluating the applicability and consideration for its utilization in state‐of‐the‐art clean coal technology, IGCC. This paper particularly discusses the eligibility of Polish lignite from the perspective of the fusibility and fluidity of ash melts and the fundamental drying kinetics of lignite in superheated steam in the light of water removal. The viscosity of ash melts is measured at high temperature up to 1700 °C. In the drying tests, the significant influence of structural issues, because of the provenance and origin of lignite on the drying characteristics, was found by applying the method of sensitivity analysis of physical propensity. This paper concludes that the investigated Polish lignite has characteristics favourable for utilization in IGCC technology, once the precautions related to its high moisture have been carefully addressed. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
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