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NFATc4 and ATF3 Negatively Regulate Adiponectin Gene Expression in 3T3-L1 Adipocytes
Kim, H. B.,Kong, M.,Kim, T. M.,Suh, Y. H.,Kim, W.-H.,Lim, J. H.,Song, J. H.,Jung, M. H. American Diabetes Association 2006 Diabetes Vol.55 No.5
<P>Expression of adiponectin decreases with obesity and insulin resistance. At present, the mechanisms responsible for negatively regulating adiponectin expression in adipocytes are poorly understood. In this investigation, we analyzed the effects of 5' serial deletion constructs on the murine adiponectin promoter. Here, we identified the repressor region located between -472 and -313 bp of the promoter. Removal of the putative nuclear factor of activated T-cells (NFATs) binding site increased the promoter activity, and overexpression of NFATc4 reduced the promoter activity. Treatment with the calcium ionophore A23187, an activator of NFAT, reduced mRNA as well as promoter activity. The binding of NFATc4 to the promoter was associated with increased recruitment of histone deacetylase 1 and reduced acetylation of histone H3 at the promoter site. In addition, binding of activating transcription factor 3 (ATF3) to the putative activator protein-1 site located adjacent to the NFAT binding site also repressed the promoter activity. Treatment with thapsigargin, an inducer of ATF3, reduced both mRNA and promoter activity. Importantly, the binding activities of NFATc4 and ATF3, increased significantly in white adipose tissues of ob/ob and db/db mice compared with controls. Taken together, this study demonstrates for the first time that NFATc4 and ATF3 function as negative regulators of adiponectin gene expression, which may play critical roles in downregulating adiponectin expression in obesity and type 2 diabetes.</P>
Kim, H.S.,Hong, M.,Ann, J.,Yoon, S.,Nguyen, C.T.,Lee, S.C.,Lee, H.Y.,Suh, Y.G.,Seo, J.H.,Choi, H.,Kim, J.Y.,Kim, K.W.,Kim, J.,Kim, Y.M.,Park, S.J.,Park, H.J.,Lee, J. Elsevier/Pergamon 2016 Bioorganic & medicinal chemistry Vol.24 No.22
Based on the lead compound L-80 (compound 2), a potent heat shock protein 90 (HSP90) inhibitor, a series of C-ring truncated deguelin analogs were designed, synthesized and evaluated for Hypoxia Inducible Factor-1α (HIF-1α) inhibition as a primary screening method. Their structure-activity relationship was investigated in a systematic manner by varying the A/B ring, linker and D/E ring, respectively. Among the synthesized inhibitors, compound 5 exhibited potent HIF-1α inhibition in a dose-dependent manner and significant antitumor activity in human non-small cell lung carcinoma (H1299), with better activities than L-80. It also inhibited in vitro hypoxia-mediated angiogenic processes in human retinal microvascular endothelial cells (HRMEC). The docking study of 5 showed a similar binding mode as L-80: it occupied the C-terminal ATP-binding pocket of HSP90, indicating that the anticancer and antiangiogenic activities of 5 were derived from HIF-1α destabilization by inhibiting the C-terminal ATP-binding site of hHSP90.
Magnetic properties of Mn12O12(O2CC4H3S)16(H2O)4 single-molecule magnet
B. J. Kim,S. Yoon,B. J. Suh,J. Kim,J. M. Lim,S. H. Phark,Y. Do,Z. G. Khim 한국물리학회 2004 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.45 No.3
We report a study of the magnetic properties of a Mn12O12(O2CC4H3S)16(H2O)4 single-molecule magnet. Polycrystalline powder samples were prepared by using a reaction of 3-thiophenecarboxylic acid with a slurry of Mn12O12(O2CCH3)16(H2O)4 (noted as Mn12-Ac) in methylene chloride. Magnetization measurements were performed down to 2 K with a magnetic eld of up to 6 T. The magnetization curves showed a superparamagnetic behavior above the blocking temperature TB and became hysteric below TB due to the magnetic anisotropy of the molecule. The spin and the magnetic anisotropy constant of the molecule were determined by analyzing the magnetization data, and the results agree well with those for Mn12-Ac. We also report the chemical deposition of a Mn12O12(O2CC4H3S)16(H2O)4 lm and an observation of its surface morphology by using scanning tunneling microscopy.
A novel chimeric promoter that is highly responsive to hypoxia and metals
Lee, J-Y,Lee, Y-S,Kim, J-M,Kim, K L,Lee, J-S,Jang, H-S,Shin, I-S,Suh, W,Jeon, E-S,Byun, J,Kim, D-K Nature Publishing Group 2006 Gene Therapy Vol.13 No.10
To develop a potent hypoxia-inducible promoter, we evaluated the usefulness of chimeric combinations of the (Egr-1)-binding site (EBS) from the Egr-1 gene, the metal-response element (MRE) from the metallothionein gene, and the hypoxia-response element (HRE) from the phosphoglycerate kinase 1 gene. In transient transfection assays, combining three copies of HRE (3 × HRE) with either EBS or MRE significantly increased hypoxia responsiveness. When a three-enhancer combination was tested, the EBS–MRE-3 × HRE (E–M–H) gave a hypoxia induction ratio of 69. The expression induced from E–M–H-pGL3 was 2.4-fold higher than that induced from H-pGL3 and even surpassed the expression from a human cytomegalovirus promoter-driven vector. The high inducibility of E–M–H was confirmed by validation studies in different cells and by expressing other cDNAs. Gel shift assays together with functional overexpression studies suggested that increased levels of hypoxia-inducible factor 1α, metal transcription factor-1 and Egr-1 may be associated with the high inducibility of the E–M–H chimeric promoter. E–M–H was also induced by hypoxia mimetics such as Co<SUP>2+</SUP> and deferoxamine (DFX) and by hydrogen peroxide. Gene expression from the E–M–H was reversible as shown by the reduced expression of the transgene upon removal of inducers such as hypoxia and DFX. In vivo evaluation of the E–M–H in ischemic muscle revealed that erythropoietin secretion and luciferase and LacZ expression were significantly higher in the E–M–H group than in a control or H group. With its high induction capacity and versatile means of modulation, this novel chimeric promoter should find wide application in the treatment of ischemic diseases and cancer.Gene Therapy (2006) 13, 857–868. doi:10.1038/sj.gt.3302728; published online 9 February 2006
Formation of Ag Nanostrings Induced by Lyotropic Liquid–Crystalline Phospholipid Multilayer
Kim, Suk J.,An, Hyeun H.,Lee, Seung J.,Lee, Jong H.,Kim, Young H.,Yoon, Chong S.,Suh, Sang H. American Chemical Society 2012 Langmuir Vol.28 No.1
<P>Morphological variation of the Ag nanoparticles embedded in a lyotropic phospholipid (1,2-dioleoyl-<I>sn</I>-glycero-3-phosphoethanolamine, DOPE) membrane during hydration was investigated. Hydration at 5 °C resulted in transformation of the Ag nanoparticles into a bundle of Ag nanostrings as the Ag nanoparticles conformed to the H<SUB>II</SUB> phase of the DOPE molecules. Above 30 °C, the nanoparticles quickly coarsened into large polygonal-shaped particles since high mobility of the lipid molecules overwhelmed the tendency for the Ag nanoparticles to order. The result provided an insight into the long-term stability of nanoparticles trapped in different lipid membranes depending on the structural ordering of the molecules.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/langd5/2012/langd5.2012.28.issue-1/la203721c/production/images/medium/la-2011-03721c_0008.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/la203721c'>ACS Electronic Supporting Info</A></P>
서창호,차인호,김진권,이의웅,김형준,이병인 大韓顎顔面成形再建外科學會 1995 Maxillofacial Plastic Reconstructive Surgery Vol.17 No.4
Thyroid carcinomas are usually classified as papillary thyroid carcinoma, follicular thyroid carcinoma, medullary thyroid carcinoma and anaplastic thyroid carcinoma. Among the thyroid carcinomas, the incidence of medullary and anaplastic thyroid carcinoma is low, but the rate of lymph node & distant metastasis from them are more common compared to other types. Follicular thyroid carcinoma has a low rate of lymph node metastasis as 10% and has a high occurrence of hematogenous metastasis to lung, bone, brain and liver. Papillary thyroid carcinoma accounts for 60∼70% of whole thyroid carcinomas and the cervical lymph node metastasis is 21∼81% including micrometastasis, but the distant metastasis is rare. In the case of bone metastasis, follicular type reveals most frequent, and the rate is about 5%, and more likely to be found on vertebra, pelvis, ribs, femur, and skull. The clinical symptoms of bone metastasis are pain, swelling, pathological fracture and radiologically osteolytic lesions can be observed. But distant metastasis of papillary thyroid carcinoma is very rare and especially, bone metastasis has hardly been reported. The treatment modalities of metastatic thyroid carcinoma to mandible are known as follows : thyroidectomy to treat primary site, resection of the affected site of mandible, external beam radiotherapy and radioiodine therapy etc.