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21.
Minami Yamauchi Toshihiro Sato Ayana Otake Masaki Kumondai Yu Sato Masafumi Kikuchi Masamitsu Maekawa Hiroaki Yamaguchi Takaaki Abe Nariyasu Mano 《International journal of molecular sciences》2022,23(15)
Patients with liver diseases not only experience the adverse effects of liver-metabolized drugs, but also the unexpected adverse effects of renally excreted drugs. Bile acids alter the expression of renal drug transporters, however, the direct effects of bile acids on drug transport remain unknown. Renal drug transporter organic anion-transporting polypeptide 4C1 (OATP4C1) was reported to be inhibited by chenodeoxycholic acid. Therefore, we predicted that the inhibition of OATP4C1-mediated transport by bile acids might be a potential mechanism for the altered pharmacokinetics of renally excreted drugs. We screened 45 types of bile acids and calculated the IC50, Ki values, and bile acid–drug interaction (BDI) indices of bile acids whose inhibitory effect on OATP4C1 was >50%. From the screening results, lithocholic acid (LCA), glycine-conjugated lithocholic acid (GLCA), and taurine-conjugated lithocholic acid (TLCA) were newly identified as inhibitors of OATP4C1. Since the BDI index of LCA was 0.278, LCA is likely to inhibit OATP4C1-mediated transport in clinical settings. Our findings suggest that dose adjustment of renally excreted drugs may be required in patients with renal failure as well as in patients with hepatic failure. We believe that our findings provide essential information for drug development and safe drug treatment in clinics. 相似文献
22.
Kazuhiro Maeta Manal Farea Hisahide Nishio Masafumi Matsuo 《International journal of molecular sciences》2022,23(9)
Antisense oligonucleotides (ASOs) are agents that modulate gene function. ASO-mediated out-of-frame exon skipping has been employed to suppress gene function. Myostatin, encoded by the MSTN gene, is a potent negative regulator of skeletal muscle growth. ASOs that induce skipping of out-of-frame exon 2 of the MSTN gene have been studied for their use in increasing muscle mass. However, no ASOs are currently available for clinical use. We hypothesized that ASOs against the splicing enhancer sequence within exon 1 of the MSTN gene would inhibit maturation of pre-mRNA, thereby suppressing gene function. To explore this hypothesis, ASOs against sequences of exon 1 of the MSTN gene were screened for their ability to reduce mature MSTN mRNA levels. One screened ASO, named KMM001, decreased MSTN mRNA levels in a dose-dependent manner and reciprocally increased MSTN pre-mRNA levels. Accordingly, KMM001 decreased myostatin protein levels. KMM001 inhibited SMAD-mediated myostatin signaling in rhabdomyosarcoma cells. Remarkably, it did not decrease GDF11 mRNA levels, indicating myostatin-specific inhibition. As expected, KMM001 enhanced the proliferation of human myoblasts. We conclude that KMM001 is a novel myostatin inhibitor that inhibits pre-mRNA maturation. KMM001 has great promise for clinical applications and should be examined for its ability to treat various muscle-wasting conditions. 相似文献
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Dr. Masakazu Hachisu Dr. Akira Seko Dr. Shusaku Daikoku Dr. Yoichi Takeda Dr. Masafumi Sakono Dr. Yukishige Ito 《Chembiochem : a European journal of chemical biology》2016,17(4):300-303
In the endoplasmic reticulum (ER), nascent glycoproteins that have not acquired the native conformation are either repaired or sorted for degradation by specific quality‐control systems composed by various proteins. Among them, UDP‐glucose:glycoprotein glucosyltransferase (UGGT) serves as a folding sensor in the ER. However, the molecular mechanism of its recognition remains obscure. This study used pseudo‐misfolded glycoproteins, comprising a modified dihydrofolate reductase with artificial pyrene–cysteine moiety on the protein surface (pDHFR) and Man9GlcNAc2‐methotrexate (M9‐MTX). All five M9‐MTX/pDHFR complexes, with a pyrene group at different positions, were found to be good substrates of UGGT, irrespective of the site of pyrene modification. These results suggest UGGT's mode of substrate recognition is fuzzy, thus allowing various glycoproteins to be accommodated in the folding cycle. 相似文献
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Loi Tonthat Hajime Saito Ryuhei Miyamoto Masafumi Suzuki Noboru Yoshimura Kazutaka Mitobe 《IEEJ Transactions on Electrical and Electronic Engineering》2015,10(Z1):S1-S6
Recently, the use of a ferromagnetic material in a soft‐heating method has garnered much attention as a novel method for cancer treatment. By concurrently using this material as a thermal probe, we are currently developing a minimally invasive heating and wireless temperature measurement system. To make the approach feasible in a clinical setting, it is vital to overcome the key challenge of heating the local tumor at a constant temperature. In previous conventional approaches, it was necessary to switch the induction‐heating power supply on/off after the target tumor temperature was reached. However, it cannot determine the temperature of the material during the power‐off period. Therefore, we changed this approach and found that by adjusting the distance between the heating coil and the material while maintaining a constant current flow in heating coil, the drift problem, which happened just after power is supplied during the on/off operation, did not occur any longer. Accordingly, it was not required to use multiple sensors to reduce the drift, thereby minimizing the cost. This study verifies the validity of our wireless thermometry approach while performing rotary scanning and proposes a technique for determining achievement of the target temperature. This knowledge complements other approaches for cancer treatment utilizing hyperthermia. © 2015 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc. 相似文献
28.
Ninomiya Yuma Sasaki Hideaki Yoshikawa Takeshi Maeda Masafumi 《Metallurgical and Materials Transactions B》2019,50(1):407-415
Metallurgical and Materials Transactions B - The dissolution and passivation of pure Cu and Cu-5 wt pct Ag anodes in H2SO4-CuSO4 electrolyte were investigated by a direct... 相似文献
29.
Rates of formation of gases, oils, asphaltenes and preasphaltenes during non-solvent liquefaction of coal over molten tin catalyst have been measured. A probable reaction scheme and the rate constants for the pathways comprising the scheme have been presented. The results show that the catalyst greatly accelerates the conversion of preasphaltenes to asphaltenes. It also accelerates two other reactions, i.e., coal to preasphaltenes and coal to asphaltenes. By contrast, the catalyst does little to promote gasification and formation of oils. 相似文献
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