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1.
Hideaki Kaneto Tomohiko Kimura Atsushi Obata Masashi Shimoda Kohei Kaku 《International journal of molecular sciences》2021,22(5)
While there are various kinds of drugs for type 2 diabetes mellitus at present, in this review article, we focus on metformin which is an insulin sensitizer and is often used as a first-choice drug worldwide. Metformin mainly activates adenosine monophosphate-activated protein kinase (AMPK) in the liver which leads to suppression of fatty acid synthesis and gluconeogenesis. Metformin activates AMPK in skeletal muscle as well, which increases translocation of glucose transporter 4 to the cell membrane and thereby increases glucose uptake. Further, metformin suppresses glucagon signaling in the liver by suppressing adenylate cyclase which leads to suppression of gluconeogenesis. In addition, metformin reduces autophagy failure observed in pancreatic β-cells under diabetic conditions. Furthermore, it is known that metformin alters the gut microbiome and facilitates the transport of glucose from the circulation into excrement. It is also known that metformin reduces food intake and lowers body weight by increasing circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15). Furthermore, much attention has been drawn to the fact that the frequency of various cancers is lower in subjects taking metformin. Metformin suppresses the mechanistic target of rapamycin (mTOR) by activating AMPK in pre-neoplastic cells, which leads to suppression of cell growth and an increase in apoptosis in pre-neoplastic cells. It has been shown recently that metformin consumption potentially influences the mortality in patients with type 2 diabetes mellitus and coronavirus infectious disease (COVID-19). Taken together, metformin is an old drug, but multifaceted mechanisms of action of metformin have been unraveled one after another in its long history. 相似文献
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Tetsuya Iida Dr. Yukihiro Itoh Yukari Takahashi Dr. Yasunobu Yamashita Dr. Takashi Kurohara Dr. Yuka Miyake Prof. Makoto Oba Prof. Takayoshi Suzuki 《ChemMedChem》2021,16(10):1609-1618
Lysine demethylase 5 C (KDM5C) controls epigenetic gene expression and is attracting great interest in the field of chemical epigenetics. KDM5C has emerged as a therapeutic target for anti-prostate cancer agents, and recently we identified triazole 1 as an inhibitor of KDM5C. Compound 1 exhibited highly potent KDM5C-inhibitory activity in in vitro enzyme assays, but did not show strong anticancer effects. Therefore, a different approach is needed for the development of anticancer agents targeting KDM5C. Here, we attempted to identify KDM5C degraders by focusing on a protein-knockdown strategy. Compound 3 b , which was designed based on compound 1 , degraded KDM5C and inhibited the growth of prostate cancer PC-3 cells more strongly than compound 1 . These findings suggest that KDM5C degraders are more effective as anticancer agents than compounds that only inhibit the catalytic activity of KDM5C. 相似文献
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Tomoko Okuyama Jun Shirakawa Kazuki Tajima Yoko Ino Heidrun Vethe Yu Togashi Mayu Kyohara Ryota Inoue Daisuke Miyashita Jinghe Li Nozomi Goto Taiga Ichikawa Shingo Yamasaki Haruka Ohnuma Rie Takayanagi Yayoi Kimura Hisashi Hirano Yasuo Terauchi 《International journal of molecular sciences》2020,21(21)
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Sato Tetsuya Yamani Yusuke Liechty Molly Chancey Eric T. 《Cognition, Technology & Work》2020,22(2):399-407
Cognition, Technology & Work - Trust is a critical construct that influences human–automation interaction in multitasking workspaces involving imperfect automation. Karpinsky et al. (Appl... 相似文献
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The World robot summit disaster robotics category – achievements of the 2018 preliminary competition
Satoshi Tadokoro Tetsuya Kimura Masayuki Okugawa Katsuji Oogane Hiroki Igarashi Yoshikazu Ohtsubo 《Advanced Robotics》2019,33(17):854-875
The World Robot Summit is a robot Olympics and aims to be held in a different country every four years from 2020. The concept of the Plant Disaster Prevention challenge is daily inspections, checks, and emergency response in industrial plants, and in this competition, robots must carry out these types of missions in a mock-up plant. The concept of the Tunnel Disaster Response and Recovery challenge is emergency response to tunnel disasters, and is a simulation competition whereby teams compete to show their ability to deal with disasters, by collecting information and removing debris. The Standard Disaster Robotics challenge assesses, in the form of a contest, the standard performance levels of a robot that are necessary for disaster prevention and emergency response. The World Robot Summit Preliminary Competition was held at Tokyo Big Sight in October 2018, and 36 teams participated in the Disaster Robotics Category. UGVs and UAVs contended the merits of new technology for solving complex problems, using core technologies such as mobility, sensing, recognition, performing operations, human interface, autonomous intelligence etc., as well as system integration and implementation of strategies for completing missions, gaining high-level results. 相似文献
8.
Shoji Nakamura Yuji Shibahara Atsushi Kimura Osamu Iwamoto Akihiro Uehara Toshiyuki Fujii 《Journal of Nuclear Science and Technology》2020,57(4):388-400
ABSTRACTThe thermal-neutron capture cross-section (σ0) and resonance integral (I0) were measured for the 135Cs(n,γ)136Cs reaction by an activation method and mass spectrometry. Because of difficulty in the preparation of pure 135Cs samples, we used 135Cs contained as an impurity in a normally available 137Cs standard solution. An isotope ratio of 135Cs and 137Cs in a standard 137Cs solution was measured by mass spectrometry to quantify 135Cs. Cesium-135 impurity along with the 137Cs standard solution was irradiated at the hydraulic conveyer of the research reactor in the Institute for Integral Radiation and Nuclear Science, Kyoto University. Wires of Co/Al and Au/Al alloys were used as neutron monitors to measure thermal-neutron fluxes and epi-thermal Westcott’s indices at an irradiation position. A gadolinium filter was used to measure the σ0, and a value of 0.133 eV was taken as the cut-off energy. Gamma-ray spectroscopy was used to measure induced activities of 137Cs, 136Cs and monitor wires. On the basis of Westcott’s convention, the σ0 and I0 values were derived as 8.57 ± 0.25 barn, and 45.3 ± 3.2 barn, respectively. The value of σ0 obtained in the present study agreed within the limits of uncertainties with the past-reported value of 8.3 ± 0.3 barn. 相似文献
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Akinobu Takaki Tetsuya Yasunaka Takahito Yagi 《International journal of molecular sciences》2015,16(8):17494-17513
Hepatitis B often progresses to decompensated liver cirrhosis requiring orthotopic liver transplantation (OLT). Although newer nucleos(t)ide analogues result in >90% viral and hepatitis activity control, severely decompensated patients still need OLT because of drug-resistant virus, acute exacerbation, or hepatocellular carcinoma. Acute hepatitis B is also an indication for OLT, because it can progress to fatal acute liver failure. After OLT, the hepatitis B recurrence rate is >80% without prevention, while >90% of transplant recipients are clinically controlled with combined hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogue treatment. However, long-term HBIG administration is associated with several unresolved issues, including limited availability and extremely high cost; therefore, several treatment protocols with low-dose HBIG, combined with nucleos(t)ide analogues, have been investigated. Another approach is to induce self-producing anti-hepatitis B virus (HBV) antibodies using an HBV envelope (HBs) antigen vaccine. Patients who are not HBV carriers, such as those with acutely infected liver failure, are good candidates for vaccination. For chronic HBV carrier liver cirrhosis patients, a successful vaccine response can only be achieved in selected patients, such as those treated with experimentally reduced immunosuppression protocols. The present protocol for post-OLT HBV control and the future prospects of newer treatment strategies are reviewed. 相似文献