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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
2.
Ryo Hashikawa Yasuhiro Fujii Atsushi Kinomura Takeshi Saito Arifumi Okada Takashi Wakasugi Kohei Kadono 《Journal of the American Ceramic Society》2019,102(4):1642-1651
Radiophotoluminescence phenomena have been widely investigated on various types of materials for dosimetry applications. We report that an aluminoborosilicate glass containing 0.005 mol% copper exhibits intense photoluminescence in the visible region induced by X-ray and γ-ray irradiation. The luminescence is assigned to the 3d94s1 → 3d10 transition of Cu+. The proportionality of the intensity of the induced photoluminescence to the irradiation dose was confirmed up to 0.5 kGy using 60Co γ-ray irradiation. Based on the spectroscopic results, a potential mechanism was proposed for the enhancement of the photoluminescence. The exposure to the ionizing radiation generates electron-hole pairs in the glass, and the electrons are subsequently captured by the Cu2+ ions, which are converted to Cu+ and emit the luminescence. For the glass containing 0.01 mol% copper, the pronounced enhancement of the photoluminescence was not observed because the reverse reaction, ie, the capture of the holes by the Cu+ ions, becomes prominent. The photoluminescence induced by the irradiation was stably observed for the glasses kept at room temperature and even for the glasses heat-treated at 150°C. However, the induced photoluminescence could be eliminated by the heat treatment at a temperature at 500°C, and the glass returned to the initial pre-irradiation state. The Cu-doped aluminoborosilicate glass is a potential candidate for use in dosimetry applications. 相似文献
3.
4.
T Tagami K Tanaka H Sugawa H Nakamura Y Miyoshi T Mori K Nakao 《Canadian Metallurgical Quarterly》1996,43(6):689-699
MIcrospheres containing diclofenac sodium (DS) were prepared using carboxymethylcellulose (CMC) as the main support material (1.0, 2.0, 3.0% (w/v)) and aluminum chloride as the crosslinker. Drug to polymer ratios of 1:1, 1:2 and 1:4 were used to obtain a range of microspheres. The microspheres were then coated with an enteric coating material, Eudragit S-100, efficiency, % yield value, particle sizes an in-vitro dissolution behaviour were investigated. The surface of the enteric coated microspheres seemed to be all covered with Eudragit S-100 from scanning electron microscopy observation. It was also observed that increasing the CMC concentration led to an increase in the encapsulation efficiency, % yield value and particle size and decreased the release rate. Eudragit S-100 coating did not significantly alter the size but the release rate was significantly lower even when the lower concentration solution was used. 相似文献
5.
M Suda K Tanaka K Natsui T Usui I Tanaka M Fukushima C Shigeno J Konishi S Narumiya A Ichikawa N Nakao 《Canadian Metallurgical Quarterly》1996,137(5):1698-1705
PGE2 is one of the key molecules in the osteoblast. It is the major prostanoid in the bone, and its production is under the control of both systemic and local factors. PGE2 has been reported to have multiple actions in the osteoblast, such as growth promotion and cell differentiation. To better understand the action of PGE2 in the osteoblast, we determined the PGE receptor subtypes in MC3T3-E1, an osteoblastic cell line derived from the normal mouse calvaria. Northern blot analysis revealed that EP1 and EP4 subtypes are expressed in MC3T3-E1. In contrast, EP3 subtype was not detected by either Northern blot analysis or RT-PCR. The contribution of each subtype was evaluated by studying the effects of subtype-specific analogs on osteoblastic function at confluency and 5 days after confluency. An EP1 agonist, 17-phenyl-omega-trinor PGE2, increased DNA synthesis and decreased alkaline phosphatase activity. 11-Deoxy-PGE1, and EP2 and EP4 agonist, decreased DNA synthesis and increased alkaline phosphatase activity at both stages. Butaprost, an EP2-selective agonist, showed effects similar to those of 11-deoxy-PGE1 only at confluency. Another and more differentiated osteoblastic marker, osteocalcin production, was detectable and was stimulated by 11-deoxy-PGE1 only 5 days after confluency. The exposure of these cells to EP1 agonist changed the cell shape to a more fibroblastic appearance. These results indicate that EP1, EP4, and probably EP2 are present in MC3T3-E1 cells; EP1 promotes cell growth, and EP2 and EP4 mediate differentiation of the osteoblast. Furthermore, the decreased response to EP2-specific agonist 5 days after confluency suggests that the expression of PGE receptor subtype is dependent on the stage of osteoblastic differentiation. This is the first report to determine PGE receptor subtypes in the bone. 相似文献
6.
Motofumi Suzuki Kohei Kinoshita Shinji Jomori Hidehiko Harada Kaoru Nakajima Kenji Kimura 《Thin solid films》2007,515(22):8281-8284
The initial stage of iron silicide formation is investigated by high-resolution Rutherford backscattering spectroscopy. During the Fe deposition on Si(001) at 470 °C, the formation of FeSi2 is confirmed by the surface peak analysis. Initially, FeSi2 grows epitaxially so that one of the major crystallographic axes is parallel to the <111> axis of the Si substrate. With increasing Fe deposition, the deviation between the major crystallographic axis of the silicide region and Si<111> increases although the electron diffraction pattern is independent of the amount of Fe deposition. Therefore, the subsurface crystallographic structure of iron silicide is transformed from a cubic-like to a low-symmetry structure. 相似文献
7.
A mica-based machinable glass-ceramic has been converted to a glass-ceramic containing cordiertie and body-centered cubic chondrodite through heat treatment at temperatures higher than that used for the crystallization of mica. The machinability is lost, microhardness increases, and the thermal expansion coefficient decreases with the change of the crystalline phase from mica to cordierite and chondrodite. 相似文献
8.
Tomoyasu Nakamine Shugo Suzuki Kenji Nakao Makoto Okazaki 《Fullerenes, Nanotubes and Carbon Nanostructures》1995,3(4):389-398
respectively. 相似文献
9.
A unique substrate MCPM (Mitsubishi Copper Polyimide Metal-base) technology has been developed by applying our basic copper/polyimide
technology.1 This new substrate technology MCPM is suited for a high-density, multi-layer, multi-chip, high-power module/package, such
as used for a computer. The new MCPM was processed using a copper metal base (110 × 110 mm), full copper system (all layers)
with 50-μm fine lines. As for pad metallizations for the IC assembly, we evaluated both Ni/Au for chip and wire ICs and solder
for TAB ICs. The total number of assembled ICs is 25. To improve the thermal dispersion, copper thermal vias are simultaneously
formed by electro-plating. This thermal via is located between the IC chip and copper metal base, and promotes heat dispersion.
We employed one large thermal via (4.5 mm?) and four small vias (1.0 mm?) for each IC pad. The effect of thermal vias and/or base metal is simulated by a computer analysis and compared with an alumina
base substrate. The results show that the thermal vias are effective at lowering the temperature difference between the IC
and base substrate, and also lowering the temperature rise of the IC chip. We also evaluated the substrate’s reliability by
adhesion test, pressure cooker test, etc. 相似文献
10.
This paper describes the development of a novel automatic FEM mesh generation algorithm based on the fuzzy knowledge processing technique.A number of local nodal patterns are stored in a nodal pattern database of the mesh generation system. These nodal patterns are determined a priori based on certain theories or past experience of experts of FEM analyses. For example, such human experts can determine certain nodal patterns suitable for stress concentration analyses of cracks, corners, holes and so on. Each nodal pattern possesses a membership function and a procedure of node placement according to this function. In the cases of the nodal patterns for stress concentration regions, the membership function which is utilized in the fuzzy knowledge processing has two meanings, i.e. the closeness of nodal location to each stress concentration field as well as nodal density. This is attributed to the fact that a denser nodal pattern is required near a stress concentration field. What a user has to do in a practical mesh generation process are to choose several local nodal patterns properly and to designate the maximum nodal density of each pattern. After those simple operations by the user, the system places the chosen nodal patterns automatically in an analysis domain and on its boundary, and connects them smoothly by the fuzzy knowledge processing technique. Then triangular or tetrahedral elements are generated by means of the advancing front method. The key issue of the present algorithm is an easy control of complex two- or three-dimensional nodal density distribution by means of the fuzzy knowledge processing technique.To demonstrate fundamental performances of the present algorithm, a prototype system was constructed with one of object-oriented languages, Smalltalk-80 on a 32-bit microcomputer, Macintosh II. The mesh generation of several two- and three-dimensional domains with cracks, holes and junctions was presented as examples. 相似文献