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Lee, Ki Mo,Lee, Eun Ok,Lee, Yu Ran,Joo, Hee Kyoung,Park, Myoung Soo,Kim, Cuk-Seong,Choi, Sunga,Jeong, Jin-Ok,Jeon, Byeong Hwa MDPI 2017 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.18 No.10
<P>Vascular calcification plays a role in the pathogenesis of atherosclerosis, diabetes, and chronic kidney disease; however, the role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) in inorganic phosphate (Pi)-induced vascular smooth muscle cell (VSMC) calcification remains unknown. In this study, we investigated the possible role of APE1/Ref-1 in Pi-induced VSMC calcification. We observed that Pi decreased endogenous APE1/Ref-1 expression and promoter activity in VSMCs, and that adenoviral overexpression of APE1/Ref-1 inhibited Pi-induced calcification in VSMCs and in an ex vivo organ culture of a rat aorta. However, a redox mutant of APE1/Ref-1(C65A/C93A) did not reduce Pi-induced calcification in VSMCs, suggesting APE1/Ref-1-mediated redox function against vascular calcification. Additionally, APE1/Ref-1 overexpression inhibited Pi-induced intracellular and mitochondrial reactive oxygen species production, and APE1/Ref-1 overexpression resulted in decreased Pi-induced lactate dehydrogenase activity, pro-apoptotic Bax levels, and increased anti-apoptotic Bcl-2 protein levels. Furthermore, APE1/Ref-1 inhibited Pi-induced osteoblastic differentiation associated with alkaline phosphatase activity and inhibited Pi-exposure-induced loss of the smooth muscle phenotype. Our findings provided valuable insights into the redox function of APE1/Ref-1 in preventing Pi-induced VSMC calcification by inhibiting oxidative stress and osteoblastic differentiation, resulting in prevention of altered osteoblastic phenotypes in VSMCs.</P>
미끄럼 마찰시 생성되는 고탄소강의 열변형층이 트라이볼로지 특성에 미치는 영향
이성애(Sungae Lee),조대현(Daehyun Cho),이영제(Youngze Lee) 한국트라이볼로지학회 2009 한국트라이볼로지학회 학술대회 Vol.2009 No.6
There have been many studies about white layers generated in various manufacturing processes such as hard turning, grinding, reaming. There are two different opinions on its wear characteristics. It is considered to be tribological adventage in some instance, but should decrease wear resistance because of forming micro crack and void. In this study, Ball-on-Disk type tester was used for sliding test with SUJ2 specimen due to understand the effect of white layer on friction and wear property. Surface profiler was used for investigating change of surface profiles, and transformation of micro structure was observed by FE-SEM on cross section of specimen after chemical etching.
Lee, Yu Ran,Lim, Jae Sung,Shin, Ju Hyun,Choi, Sunga,Joo, Hee Kyoung,Jeon, Byeong Hwa Korean Continence Society 2016 International Neurourology Journal Vol.20 No.1
<P><B>Purpose:</B></P><P>Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in DNA repair and redox modulation. Recently, serum and urinary APE1/Ref-1 levels were reported to be increased in patients with bladder cancer. Genetic variations of APE/Ref-1 are associated with the risk of cancer. However, the effect of <I>APE1/Ref-1</I> variants on its secretory activity is yet unknown.</P><P><B>Methods:</B></P><P><I>APE1/Ref-1</I> variants were evaluated by DNA sequencing analysis of reverse transcription polymerase chain reaction products in coding DNA sequences (CDS) of APE1/Ref-1 in bladder tissue samples from patients with bladder cancer (n=10). Secretory activity of <I>APE1/Ref-1</I> variants was evaluated with immunoblot and enzyme-linked immunosorbent assay of the culture medium supernatants.</P><P><B>Results:</B></P><P>Four different substitution mutants (D148E, I64V/D148E, W67R/D148E, and E86G/D148E) of APE1/Ref-1 were identified in bladder cancer specimens. However, deletion mutants of APE1/Ref-1 CDS were not found. The secretory activity of the <I>APE1/Ref-1</I> variants (D148E, I64V/D148E, and E86G/D148E) was increased compared to that of wild type APE1/Ref-1. Furthermore, the secretory activity in basal or hyperacetylated conditions was much higher than that in <I>APE1/Ref-1</I> D148E-transfected HEK293 cells.</P><P><B>Conclusions:</B></P><P>Taken together, our data suggest that the increased secretory activity of D148E might contribute to increased serum levels of APE1/Ref-1 in patients with bladder cancer.</P>
Lee, Yu Ran,Kim, Ki Mo,Jeon, Byeong Hwa,Choi, Jong Woon,Choi, Sunga D.A. Spandidos 2012 International journal of molecular medicine Vol.29 No.5
<P>Naematoloma sublateritium (Fr.) P. Karst is a chestnut mushroom that is currently a popular edible fungus in the USA, Japan, China and Korea. Although its therapeutic potential in the treatment of diseases has been demonstrated, the pharmacological effect of N.?sublateritium (NS) has been poorly studied. In the present study, we demonstrate for the first time that NS suppresses TNF-α-induced inflammatory response in human umbilical vein endothelial cells. The n-butanol fraction of NS (BFNS) inhibited TNF-α-induced monocyte adhesion to endothelial cells in a dose-dependent manner. The anti-adhesive activity of BFNS correlated with suppressed expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, monocyte chemoattractant protein-1 and interleukin-8 at both the mRNA and protein levels. In addition, BFNS dose-dependently decreased the expression of inducible nitrogen oxygen synthase (iNOS) and cyclooxygenase-2 (COX-2). Notably, BFNS significantly regulated the nuclear factor (NF)-κB transcriptional activity that was activated by TNF-α stimulation. When considered together, these results suggest that BFNS inhibits the expression of TNF-α-induced adhesion molecules in addition to regulating the iNOS/COX-2 pathways through the modulation of NF-κB in endothelial cells. In conclusion, we propose that BFNS may be a potential therapeutic agent against vascular inflammation, such as atherosclerosis.</P>
Lee, Yu Ran,Kim, Ki Mo,Jeon, Byeong Hwa,Choi, Sunga Lychnia 2014 International journal of oncology Vol.45 No.3
<P>Naematoloma sublateritium (Fr.) P. Karst is a basidiomycete that has been used as traditional medicine. N. sublateritium produces a triterpenoid antitumor compound, clavaric acid, but, in general, the effects of N. sublateritium constituents against tumor invasion and metastasis have been poorly studied. To investigate the inhibitory effect of N. sublateritium constituents on highly invasive and metastatic tumor cells, the TNF-alpha-stimulated human breast cancer cell line, MDA-MB-231 was treated with the hexane fraction of an N. sublateritium extract (HFNS). Non-cytotoxic concentrations of HFNS markedly inhibited the invasion and migration of the MDA-MB-231 cells in the Matrigel invasion assay and wound-healing analysis, respectively. Gelatin zymography showed that HFNS suppressed the activity of MMP-9, but not of MMP-2. Immunoblotting demonstrated that treatment with HFNS had decreased the level of MMP-9 and urokinase plasminogen activator-1 (uPA-1), but had upregulated expression of the endogenous inhibitor proteins, including TIMP-1,-2, and PAT-1, in a dose-dependent manner. Furthermore, HFNS suppressed the phosphorylation of p38 and JNK1/2, but not that of ERK1/2. This was confirmed by pretreatment of cells with specific inhibitors prior to stimulation with TNF-alpha. HFNS treatment also led to a dose-dependent inhibition of the DNA-binding activities of AP-1 and NF kappa B, which are downstream targets of JNK and p38. These data suggested that HFNS inhibits the metastatic potential of MDA-MB-231 cells by inhibiting the phosphorylation of JNK/p38 and reducing AP-1 and NF kappa B DNA-binding activities. Therefore, HFNS may be a potential therapeutic agent against metastasis of breast cancer.</P>
ATP Binding Cassette Transporter A1 is Involved in Extracellular Secretion of Acetylated APE1/Ref-1
Lee, Yu Ran,Joo, Hee Kyoung,Lee, Eun Ok,Cho, Hyun Sil,Choi, Sunga,Kim, Cuk-Seong,Jeon, Byeong Hwa MDPI AG 2019 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.20 No.13
<P>Acetylation of nuclear apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE1/Ref-1) is associated with its extracellular secretion, despite the lack of an N-terminal protein secretion signal. In this study, we investigated plasma membrane targeting and translocation of APE1/Ref-1 in HEK293T cells with enhanced acetylation. While APE1/Ref-1 targeting was not affected by inhibition of the endoplasmic reticulum/Golgi-dependent secretion, its secretion was reduced by inhibitors of ATP-binding cassette (ABC) transporters, and siRNA-mediated down-regulation of ABC transporter A1. The association between APE1/Ref-1 and ABCA1 transporter was confirmed by proximal ligation assay and immunoprecipitation experiments. An APE1/Ref-1 construct with mutated acetylation sites (K6/K7R) showed reduced co-localization with ABC transporter A1. Exposure of trichostatin A (TSA) induced the acetylation of APE1/Ref-1, which translocated into membrane fraction. Taken together, acetylation of APE1/Ref-1 is considered to be necessary for its extracellular targeting via non-classical secretory pathway using the ABCA1 transporter.</P>
Kim Sungae,Hong Jamin,Lee Yongseong,Son Daegu 대한성형외과학회 2022 Archives of Plastic Surgery Vol.49 No.2
Background Population aging has led to an increased incidence of pressure ulcers, resulting in a social burden and economic costs. We developed a three-dimensional knitted fabric (3-DKF) with a pressure-reducing function that can be applied topically in the early stages of pressure ulcers to prevent progression.Methods We evaluated the effects of the 3-DKF in a streptozotocin-induced diabetes mellitus pressure ulcer mouse model, and the fabric was preliminarily applied to patients. Twelve-week-old male C57BL/6 mice were used for the animal experiments. In the pressure ulcer mouse model, an ischemia-reperfusion injury was created using a magnet on the dorsa of the mice. Pressure was measured with BodiTrak before and after applying the 3-DKF to 14 patients at risk of sacral pressure ulcers.Results In the 3-DKF-applied mice group, the ulcers were shallower and smaller than those in the control group. Compared with the mice in the control group, the 3-DKF group had lower platelet-derived growth factor-α and neutrophil elastase expression, as parameters related to inflammation, and increased levels of transforming growth factor (TGF)-β1, TGF-β3, proliferating cell nuclear antigen, and α-smooth muscle actin, which are related to growth factors and proliferation. Additionally, typical normal tissue staining patterns were observed in the 3-DKF group. In the preliminary clinical analysis, the average skin pressure was 26.2 mm Hg before applying the 3-DKF, but it decreased to an average of 23.4 mm Hg after 3-DKF application.Conclusion This study demonstrated that the newly developed 3-DKF was effective in preventing pressure ulcers through testing in a pressure ulcer animal model and preliminary clinical application.