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GPR119: a promising target for nonalcoholic fatty liver disease
Yang, Jin Won,Kim, Hyo Seon,Im, Ji Hye,Kim, Ji Won,Jun, Dae Won,Lim, Sung Chul,Lee, Kyeong,Choi, Jong Min,Kim, Sang Kyum,Kang, Keon Wook The Federation of American Societies for Experimen 2016 The FASEB Journal Vol.30 No.1
<P>Nonalcoholic fatty liver disease is associated with metabolic syndrome and has the unique characteristic of excess lipid accumulation in liver. G-protein-coupled receptor 119 (GPR119) is a promising target for type 2 diabetes. However, the role of GPR119 activation in hepatic steatosis and its precise mechanism has not been investigated. In primary cultured hepatocytes from wild-type and GPR119 knockout (KO) mice, expression of lipogenic enzymes was elevated in GPR119 KO hepatocytes. Treatment of hepatocytes and HepG2 cells with GPR119 agonists in phase 2 clinical trials (MBX-2982 [MBX] and GSK1292263) inhibited protein expression of both nuclear and total sterol regulatory element binding protein (SREBP)-1, a key lipogenesis transcription factor. Oral administration of MBX in mice fed a high-fat diet potently inhibited hepatic lipid accumulation and expression levels of SREBP-1 and lipogenesis-related genes, whereas the hepatic antilipogenesis effects of MBX were abolished in GPR119 KO mice. MBX activated AMPK and increased Ser-372 phosphorylation of SREBP-1c, an inhibitory form of SREBP-1c. Moreover, inhibition of AMPK recovered MBX-induced down-regulation of SREBP-1. These findings demonstrate for the first time that the GPR119 ligand alleviates hepatic steatosis by inhibiting SREBP-1-mediated lipogenesis in hepatocytes.</P>
( Dae Won Jun ),( Byung Ik Kim ),( Yong Kyun Cho ),( Hong Ju Kim ),( Young Oh Kwon ),( Soo Young Park ),( Sang Young Han ),( Yang Hyun Baek ),( Sung Wook Lee ),( Yong Jin Jung ),( Hwi Young Kim ),( Wo 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1
Background: Carnitine and vitamin complex (Godex®) is widely used in patients with chronic liver disease who show elevated liver enzyme in South Korea. The purpose of this study is to identify the efficacy and safety of carnitine from entecavir combination therapy in ALT elevated Chronic Hepatitis B (CHB) patients. Methods: 130 treatment-naive patients with CHB were enrolled from 13 sites. The patients were randomly selected to the entecavir and entecavir and carnitine complex. The primary endpoint of the study is ALT normalization level after 12 months, and the secondary endpoints are rate of less than HBV DNA 300 Copies/ml and adverse event rate. Results: Among the 130 patients, 119 patients completed the study treatment. The ALT normalization at 3 months was 58.9% for the monotherapy and 95.2% for the combination therapy (P<0.0001). ALT normalization rate at 12 months was 85.7% for the monotherapy and 100% for the combination group(P=0.0019). The rate of less than HBV DNA 300 copies/ ml at 12 months was 75.9 % for the monotherapy, 70.7% for the combination and it was not statistically significant. Quantification of HBsAg level was not different between the monotherapy( 10,443 IU/mL) and combination(8,621 IU/mL) at 12 months. Changes of ELISPOT value to evaluate the INF-γ secretion by HBsAg showed the increasing trend of combination therapy compare to mono-treatment(53.3 vs. 22.2, P=0.03). There were 9 SAEs during the study period but they were not related to the study medication. In addition, there were 57 AEs with 2 minor skin rashes and 2 dyspepsias, but they were controlled by not decreasing the carnitine dose. Conclusions: ALT normalization rate was higher in carnitine complex combination group than entecavir group in CHB. And combination group is faster than entecavir mono-treatment group on ALT normalization rate. HBV DNA normalization rate and serum HBV-DNA level were not changed by carnitine complex treatment.
The role of iron in the preparation and oxygen reduction reaction activity of nitrogen-doped carbon
Yang, Dae-Soo,Song, Min Young,Singh, Kiran Pal,Yu, Jong-Sung The Royal Society of Chemistry 2015 Chemical communications Vol.51 No.12
<P>It has been considered that the presence of Fe–N in the carbon network helps to enhance oxygen reduction reaction (ORR) activity of the carbon. In this study, N-doped platelet ordered mesoporous carbon is prepared using Fe-phthalocyanine as a single precursor for nitrogen, iron and carbon sources. We show that the physical presence of Fe is not necessary to enhance the ORR activity of N-doped carbon, although Fe is required to create more active sites and to increase the electrical conductivity in the carbon framework.</P> <P>Graphic Abstract</P><P>The exact role of iron in catalyzing oxygen reduction reaction in both alkaline and acidic media is portrayed with unique platelet ordered mesoporous carbon prepared using Fe-phthalocyanine as iron, nitrogen and carbon sources. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c4cc08592b'> </P>
Yang, Jae-Heon,Yun, Mi-Young,Lee, Nam-Hee,Kim, Dae-Keun,Kim, Young-Il,Noh, Young-Hee,Kim, Tae-Youl,Yoon, Se-Won,Shin, Sang-Chul 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.11
This study examined the effects of ketorolac tromethamine (KT) and baicalein (BE) on the levels of inflammatory factors in human synoviocytes. The fibroblast-like synoviocytes (FLS) cells were used to determine the possible regulatory effects of KT and BE (KTBE) on the levels of inflammatory factors in FLS cells. In addition, the levels of TNF-$\alpha$, IL-6, and IL-$1{\beta}$ mRNA expression in FLS cells induced by a TNF-$\alpha$ and IL-$1{\beta}$ co-treatment were largely inhibited by a KTBE treatment. The level of FLS cells proliferation was increased by IL-$1{\beta}$ and TNF-$\alpha$, and strongly inhibited by KTBE treatment. The production of oxygen species (ROS) was inhibited by KTBE in FLS cells. KTBE appears to regulate the levels of mRNA that are important for regulating RA progression.
A New Fabrication Method of Aluminum Nanotube Using Anodic Porous Alumina Film as a Template
Sung, Dae Dong,Choo, Myung Sook,Noh, Ji Seok,Chin, Won Bai,Yang, Woo Sung Korean Chemical Society 2006 Bulletin of the Korean Chemical Society Vol.27 No.8
Aluminum nanotube has been fabricated by a physical vapor deposition/atmospheric pressure injection using an anodic porous alumina film as a template. The pore external-, and inside diameters and the length of the aluminum nanotubes fabricated by this method are 60 nm, 35 nm and 2 $\mu$m, respectively. The structure of the fabricated aluminum nanotubes was examined by a kind of chemical treatment as extraction of copper on the cross-sectional area of these aluminum tubes in a mixed solution of $CuCl_2$ and HCl by difference of ionization tendency between aluminum and copper. The composition of the aluminum nanotube was identified by the two dimensional Hybrid Plasma Equipment Model (HPEM) employing the inductively coupled plasma.
Improvement Effect of Soyeom Pharmacopuncture on Gout via NLRP3 Inflammasome Regulation
Sung Wook Kim,Jun Ho Lee,Hyeonjin Kim,Seong Hoon Lee,Dajeong Jeong,김혁순,이철중,Dae Yong Kim,Tae-han Yook,Gabsik Yang 대한약침학회 2022 Journal of pharmacopuncture Vol.25 No.4
Objectives: Gout is an inflammatory arthritis of the joints and soft tissues occurring due to deposition of monosodium urate (MSU) crystals, which are caused by persistent hyperuricemia. Soyeom pharmacopuncture is one treatment method that has been traditionally used for pain management in Oriental medicine. However, studies on its effect in reducing gout pain have been insufficient. Therefore, we selected Soyeom pharmacopuncture among natural products used in Korea as the new target of our study. Methods: The effects of Soyeom pharmacopuncture were examined in mouse models of acute gout induced by injection of MSU crystals into footpads. IL-1β, IL-6, and TNF-α production were examined by immunoblotting and enzyme-linked immunosorbent assay as hallmarks of NLRP3 inflammasome and cytokine activation. Results: Soyeom pharmacopuncture reduced foot edema in gout-induced mice, as well as IL-1β, nitrite, IL-6, and TNF-α production. Moreover, Soyeom pharmacopuncture also reduced MSU-induced gout inflammatory gene expressions, specifically those in the NF-kB pathway. Conclusion: Pharmacopuncture may serve as a new solution for other inflammatory diseases as well. Through active follow-up studies, we could thoroughly understand the clinical value of Soyeom pharmacopuncture.