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171.
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Ryusei Terui Yuta Yanase Dr. Hidetomo Yokoo Prof. Yoshitomo Suhara Prof. Makoto Makishima Dr. Yosuke Demizu Dr. Takashi Misawa 《ChemMedChem》2021,16(3):458-462
TGR5, a G-protein-coupled receptor (GPCR), plays an important role in several physiological functions. TGR5 activation through bile acids induces an increase in energy expenditure. Therefore, synthetic TGR5 ligands could be useful for the treatment of obesity or dyslipidemia. In this study, we designed and synthesized a set of TGR5 ligands with a 5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene (TMN) skeleton, and evaluated their TGR5 agonistic activity. We also investigated the selectivity of the synthesized compounds for TGR5 relative to the farnesoid X receptor (FXR) and retinoic acid receptor (RAR). Our results show that compound 4 b [N-(2-chlorophenyl)-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenecarboxamide] exhibited potent TGR5 agonist activity with an IC50 value of 8.4 nM without significant cytotoxicity. In addition, compound 4 b showed only slight agonistic activity toward FXR and RAR at 1 μM treatment. These data indicate that compound 4 b is a selective TGR5 agonist, and could be a promising therapeutic agent for dyslipidemia. 相似文献
173.
Koji Kamagata Christina Andica Ayumi Kato Yuya Saito Wataru Uchida Taku Hatano Matthew Lukies Takashi Ogawa Haruka Takeshige-Amano Toshiaki Akashi Akifumi Hagiwara Shohei Fujita Shigeki Aoki 《International journal of molecular sciences》2021,22(10)
There has been an increasing prevalence of neurodegenerative diseases with the rapid increase in aging societies worldwide. Biomarkers that can be used to detect pathological changes before the development of severe neuronal loss and consequently facilitate early intervention with disease-modifying therapeutic modalities are therefore urgently needed. Diffusion magnetic resonance imaging (MRI) is a promising tool that can be used to infer microstructural characteristics of the brain, such as microstructural integrity and complexity, as well as axonal density, order, and myelination, through the utilization of water molecules that are diffused within the tissue, with displacement at the micron scale. Diffusion tensor imaging is the most commonly used diffusion MRI technique to assess the pathophysiology of neurodegenerative diseases. However, diffusion tensor imaging has several limitations, and new technologies, including neurite orientation dispersion and density imaging, diffusion kurtosis imaging, and free-water imaging, have been recently developed as approaches to overcome these constraints. This review provides an overview of these technologies and their potential as biomarkers for the early diagnosis and disease progression of major neurodegenerative diseases. 相似文献
174.
Nano-structured arrays are engineered to meet the requirements of a variety of applications such as microfilters, sensors, and structural interface due to their unique mechanical characteristics, which cannot be achieved by conventional solid materials. However, it is hard to evaluate the elastic properties of nano-structured arrays owing to the discrete structure, sample size, and availability of suitable techniques. To facilitate this, we develop an advanced three-dimensional microscale vibration testing process. In the test, a specially designed three-dimensional microspecimen with tuned mass is excited by a piezoelectric actuator, and the resonance frequencies are detected by a laser device successfully. The anisotropic elastic moduli of nano-structured array composed of helical nano-springs are identified from a single spectrum. This array shows so strong characteristic anisotropy that the solid one hardly can attain. The microscale testing technique can be extended to other materials and microstructures. 相似文献
175.
Shunsuke Kato Prof. Akira Onoda Naomasa Taniguchi Prof. Ulrich Schwaneberg Prof. Takashi Hayashi 《Chembiochem : a European journal of chemical biology》2021,22(4):679-685
Directed evolution of Cp*RhIII-linked nitrobindin (NB), a biohybrid catalyst, was performed based on an in vitro screening approach. A key aspect of this effort was the establishment of a high-throughput screening (HTS) platform that involves an affinity purification step employing a starch-agarose resin for a maltose binding protein (MBP) tag. The HTS platform enables efficient preparation of the purified MBP-tagged biohybrid catalysts in a 96-well format and eliminates background influence of the host E. coli cells. Three rounds of directed evolution and screening of more than 4000 clones yielded a Cp*RhIII-linked NB(T98H/L100K/K127E) variant with a 4.9-fold enhanced activity for the cycloaddition of acetophenone oximes with alkynes. It is confirmed that this HTS platform for directed evolution provides an efficient strategy for generating highly active biohybrid catalysts incorporating a synthetic metal cofactor. 相似文献
176.
Takashi Kanno Changmin Kim Daisuke Yamanaka Ken-ichi Ishibashi Hiroshi Tanaka Naohito Ohno Yoshiyuki Adachi 《International journal of molecular sciences》2021,22(4)
Because Japanese cedar pollen (JCP) contains beta-1,3-d-glucan (BG), there is concern that its lingering presence in the atmosphere, especially during its scattering period, may cause false positives in the factor-G-based Limulus amebocyte lysate (LAL) assay used to test for deep mycosis (i.e., G-test). Hence, we examined whether the LAL assay would react positively with substances contained in JCP by using the G-test to measure JCP particles and extracts. BG was purified from the JCP extract on a BG-specific affinity column, and the percentage extractability was measured using three different BG-specific quantitative methods. The G-test detected 0.4 pg BG in a single JCP particle and 10 fg from a single particle in the extract. The percentage extractability of JCP-derived BG was not significantly different among the three quantitative methods. As the JCP particles should technically have been removed during serum separation, they should be less likely to be a direct false-positive factor. However, given that the LAL-assay-positive substances in the JCP extract were not distinguishable by the three BG-specific quantitative methods, we conclude that they may cause the background to rise. Therefore, in Japan false positives arising from JCP contamination should be considered when testing patients for deep mycosis. 相似文献
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179.
Satoshi Fujiwara Takamasa Imada Tomoya Nakagita Shinji Okada Takashi Nammoku Keiko Abe Takumi Misaka 《Food chemistry》2012,130(3):561-568
Sweet enhancing effect of neohesperidin dihydrochalcone (NHDC) or cyclamate has been reported to be synergistic in human sensory tests. However, little is known about whether these synergisms are caused by the mechanism mediated by the human sweet-taste receptor. Here, we examined the sweetness intensity of sweet tastant mixtures by measuring the responses of cultured cells stably expressing the human sweet-taste receptor. The results showed that the cell response to sucrose was synergistically potentiated by the addition of NHDC or cyclamate. Moreover, a point mutation in the transmembrane domain of hT1R3 almost completely eliminated the enhancing effects of NHDC and cyclamate. These results suggest that ligand–receptor interactions in the transmembrane domain of hT1R3 are necessary for NHDC and cyclamate to elicit the synergistic potentiation of the receptor activation. Our results may provide the foundation of a molecular basis for receptor-based synergisms of sweet tastes in mixtures of diverse sweet substances. 相似文献
180.