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51.
Yusuke Karasawa Kanako Miyano Hideaki Fujii Takaaki Mizuguchi Yui Kuroda Miki Nonaka Akane Komatsu Kaori Ohshima Masahiro Yamaguchi Keisuke Yamaguchi Masako Iseki Yasuhito Uezono Masakazu Hayashida 《Molecules (Basel, Switzerland)》2021,26(19)
Activated opioid receptors transmit internal signals through two major pathways: the G-protein-mediated pathway, which exerts analgesia, and the β-arrestin-mediated pathway, which leads to unfavorable side effects. Hence, G-protein-biased opioid agonists are preferable as opioid analgesics. Rubiscolins, the spinach-derived naturally occurring opioid peptides, are selective δ opioid receptor agonists, and their p.o. administration exhibits antinociceptive effects. Although the potency and effect of rubiscolins as G-protein-biased molecules are partially confirmed, their in vitro profiles remain unclear. We, therefore, evaluated the properties of rubiscolins, in detail, through several analyses, including the CellKeyTM assay, cADDis® cAMP assay, and PathHunter® β-arrestin recruitment assay, using cells stably expressing µ, δ, κ, or µ/δ heteromer opioid receptors. In the CellKeyTM assay, rubiscolins showed selective agonistic effects for δ opioid receptor and little agonistic or antagonistic effects for µ and κ opioid receptors. Furthermore, rubiscolins were found to be G-protein-biased δ opioid receptor agonists based on the results obtained in cADDis® cAMP and PathHunter® β-arrestin recruitment assays. Finally, we found, for the first time, that they are also partially agonistic for the µ/δ dimers. In conclusion, rubiscolins could serve as attractive seeds, as δ opioid receptor-specific agonists, for the development of novel opioid analgesics with reduced side effects. 相似文献
52.
Stereoselectivity (meso/dl ratio) of the hydrodimers (HDs) formed in cathodic reduction of acetophenones was greatly affected by ultrasonic irradiation with power higher than an ultrasonic cavitation threshold in weakly acidic solutions, while such an ultrasonic effect on stereocontrol was not observed in either strongly acidic or alkaline solutions. 相似文献
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Energy-filtering transmission electron microscopy (EFTEM) was employed for investigating interactions between rubber and ZnO particles in the accelerated vulcanization process. Combining elemental mapping and electron energy loss spectroscopy (EELS) by EFTEM enabled the characterization of the interfaces with spatial resolutions of less than 10 nm and with high elemental detection sensitivity. We found that a sulfur- and zinc-rich compound was generated around ZnO particles, and that product was then revealed to be ZnS-generated as a byproduct in the accelerated vulcanization process. Through this study, it is indicated that the accelerated vulcanization with ZnO does not occur uniformly in the rubber matrix; it occurs locally around ZnO particles at a higher reaction rate, implying that the rubber network structure is not uniform on the nanoscale. 相似文献
56.
We present a numerical approach for low Mach number combustion that conserves both mass and energy while remaining on the equation of state to a desired tolerance. We present both unconfined and confined cases, where in the latter the ambient pressure changes over time. Our overall scheme is a projection method for the velocity coupled to a multi-implicit spectral deferred corrections (SDC) approach to integrate the mass and energy equations. The iterative nature of SDC methods allows us to incorporate a series of pressure discrepancy corrections naturally that lead to additional mass and energy influx/outflux in each finite volume cell in order to satisfy the equation of state. The method is second order, and satisfies the equation of state to a desired tolerance with increasing iterations. Motivated by experimental results, we test our algorithm on hydrogen flames with detailed kinetics. We examine the morphology of thermodiffusively unstable cylindrical premixed flames in high-pressure environments for confined and unconfined cases. We also demonstrate that our algorithm maintains the equation of state for premixed methane flames and non-premixed dimethyl ether jet flames. 相似文献
57.
R Ueki K Yamaguchi H Nonaka S Sando 《Journal of the American Chemical Society》2012,134(30):12398-12401
Dopamine (DA) is a monoamine neurotransmitter that plays important roles in the brain, and whose levels in the brain are associated with several neurological and psychiatric disorders. Therefore, DA metabolism inhibitors have been used as therapeutic agents. Here, we report a (1)H NMR probe for the in situ analysis of DA metabolism, and its application to DA inhibitor screening. We designed doubly (13)C-labeled DA ((13)C(2)-DA) as the probe. The combination of the (13)C(2)-DA and (1)H-{(13)C-(13)C'} NMR technique allowed the selective and thus in situ monitoring of DA metabolism. Using (13)C(2)-DA, we successfully measured the efficacies of different inhibitors in a tissue sample, allowing us to improve the in situ inhibitory efficacy of the known DA metabolism inhibitor, clorgyline. 相似文献
58.
Seki M Tsuruta O Aoyama Y Soejima A Shimada H Nonaka H 《Chemical & pharmaceutical bulletin》2012,60(4):488-498
In investigating potent sodium (Na(+)) channel blockers for the treatment of ischemic stroke, we synthesized a novel series of 3-amino-1-(5-indanyloxy)-2-propanol derivatives and evaluated their inhibitory effects on neuronal Na(+) channels. The 3-amino-1-(5-indanyloxy)-2-propanol derivatives exhibited potent blocking activity for Na(+) channels and a significantly low affinity for dopamine D(2) receptors, which demonstrates a minimal clinical risk for extrapyramidal side effects. In particular, compound 4b, a 3-amino-1-(5-indanyloxy)-2-propanol derivative bearing a benzimidazole moiety, showed desirable neuroprotective activity in a rat transient middle cerebral artery occlusion model. Furthermore, compound 4b displayed a high binding affinity for neurotoxin receptor site 2 of the Na(+) channels, which suggests that 4b would act as a use-dependent Na(+) channel blocker in sustained depolarization during ischemic stroke. 相似文献
59.
Hidehiko Takara 《Optical and Quantum Electronics》2001,33(7-10):795-810
Recent progress in optical time-division-multiplexed (OTDM) signal generation technologies is reviewed. Optical pulse timing control, multiplexing using integrated lightwave circuits, and all-optical regularization are presented, and the possibility of over 100 Gbit/s OTDM signal generation is discussed. 相似文献
60.
Rational Design of [13C,D14]Tert‐butylbenzene as a Scaffold Structure for Designing Long‐lived Hyperpolarized 13C Probes
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Yuki Imakura Dr. Hiroshi Nonaka Dr. Yoichi Takakusagi Prof. Dr. Kazuhiro Ichikawa Nesmine R. Maptue Dr. Alexander M. Funk Prof. Dr. Chalermchai Khemtong Prof. Dr. Shinsuke Sando 《化学:亚洲杂志》2018,13(3):280-283
Dynamic nuclear polarization (DNP) is a technique to polarize the nuclear spin population. As a result of the hyperpolarization, the NMR sensitivity of the nuclei in molecules can be dramatically enhanced. Recent application of the hyperpolarization technique has led to advances in biochemical and molecular studies. A major problem is the short lifetime of the polarized nuclear spin state. Generally, in solution, the polarized nuclear spin state decays to a thermal spin equilibrium, resulting in loss of the enhanced NMR signal. This decay is correlated directly with the spin‐lattice relaxation time T1. Here we report [13C,D14]tert‐butylbenzene as a new scaffold structure for designing hyperpolarized 13C probes. Thanks to the minimized spin‐lattice relaxation (T1) pathways, its water‐soluble derivative showed a remarkably long 13C T1 value and long retention of the hyperpolarized spin state. 相似文献