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Caveolin‐1 deficiency induces premature senescence with mitochondrial dysfunction
Yu, Dongx2010,Min,Jung, Seung Hee,An, Hyoungx2010,Tae,Lee, Sungsoo,Hong, Jin,Park, Jun Sub,Lee, Hyun,Lee, Hwayeon,Bahn, Myeong‐,Suk,Lee, Hyung Chul,Han, Nax2010,Kyung,Ko, Jesang,Lee, Jae BLACKWELL PUBLISHING 2017 AGING CELL Vol.16 No.4
<P><B>Summary</B></P><P>Paradoxical observations have been made regarding the role of caveolin‐1 (Cav‐1) during cellular senescence. For example, caveolin‐1 deficiency prevents reactive oxygen species‐induced cellular senescence despite mitochondrial dysfunction, which leads to senescence. To resolve this paradox, we re‐addressed the role of caveolin‐1 in cellular senescence in human diploid fibroblasts, A549, HCT116, and Cav‐1<SUP><I>−/−</I></SUP> mouse embryonic fibroblasts. Cav‐1 deficiency (knockout or knockdown) induced cellular senescence via a p53‐p21‐dependent pathway, downregulating the expression level of the cardiolipin biosynthesis enzymes and then reducing the content of cardiolipin, a critical lipid for mitochondrial respiration. Our results showed that Cav‐1 deficiency decreased mitochondrial respiration, reduced the activity of oxidative phosphorylation complex I (CI), inactivated SIRT1, and decreased the NAD<SUP>+</SUP>/NADH ratio. From these results, we concluded that Cav‐1 deficiency induces premature senescence via mitochondrial dysfunction and silent information regulator 2 homologue 1 (SIRT1) inactivation.</P>
Kim, Taekx2010,Keun,Park, Chang Sik,Jang, Jihye,Kim, Mi Ra,Na, Heex2010,Jun,Lee, Kangseung,Kim, Hyun Jung,Heo, Kyun,Yoo, Byong Chul,Kim, Youngx2010,Myeong,Lee, Jex2010,Wook,Kim, Su Jin,Kim, Eu John Wiley and Sons Inc. 2018 MOLECULAR ONCOLOGY Vol.12 No.3
<P>The C‐type lectin‐like domain of CLEC14a (CLEC14a‐C‐type lectin‐like domain [CTLD]) is a key domain that mediates endothelial cell–cell contacts in angiogenesis. However, the role of CLEC14a‐CTLD in pathological angiogenesis has not yet been clearly elucidated. In this study, through complementarity‐determining region grafting, consecutive deglycosylation, and functional isolation, we generated a novel anti‐angiogenic human monoclonal antibody that specifically targets CLEC14a‐CTLD and that shows improved stability and homogeneity relative to the parental antibody. We found that this antibody directly inhibits CLEC14a‐CTLD‐mediated endothelial cell–cell contact and simultaneously downregulates expression of CLEC14a on the surface of endothelial cells. Using various <I>in vitro</I> and <I>in vivo</I> functional assays, we demonstrated that this antibody effectively suppresses vascular endothelial growth factor (VEGF)‐dependent angiogenesis and tumor angiogenesis of SNU182 human hepatocellular carcinoma, CFPAC‐1 human pancreatic cancer, and U87 human glioma cells. Furthermore, we also found that this antibody significantly inhibits tumor angiogenesis of HCT116 and bevacizumab‐adapted HCT116 human colorectal cancer cells. These findings suggest that antibody targeting of CLEC14a‐CTLD has the potential to suppress VEGF‐dependent angiogenesis and tumor angiogenesis and that CLEC14a‐CTLD may be a novel anti‐angiogenic target for VEGF‐dependent angiogenesis and tumor angiogenesis.</P>
Hyun Lee, Choong,Yan, Bingchun,Yoo, Kix2010,Yeon,Choi, Jung Hoon,Kwon, Seungx2010,Hae,Her, Song,Sohn, Youdong,Hwang, In Koo,Cho, Jun Hwi,Kim, Youngx2010,Myeong,Won, Moox2010,Ho Wiley Subscription Services, Inc., A Wiley Company 2011 Journal of neuroscience research Vol.89 No.7
<P><B>Abstract</B></P><P>Glucagon‐like peptide‐1 receptor (GLP‐1R) protects against neuronal damages in the brain. In the present study, ischemia‐induced changes in GLP‐1R immunoreactivity in the gerbil hippocampal CA1 region were evaluated after transient cerebral ischemia; in addition, the neuroprotective effect of the GLP‐1R agonist exendin‐4 (EX‐4) against ischemic damage was studied. GLP‐1R immunoreactivity and its protein levels in the ischemic CA1 region were highest at 1 day after ischemia/reperfusion (I/R). At 4 days after I/R, GLP‐1R immunoreactivity was hardly detected in CA1 pyramidal neurons, and its protein level was lowest. GLP‐1R protein level was increased again at 10 days after I/R, and GLP‐1R immunoreactivity was found in astrocytes and GABAergic interneurons. In addition, EX‐4 treatment attenuated ischemia‐induced hyperactivity, neuronal damage, and microglial activation in the ischemic CA1 region in a dose‐dependent manner. EX‐4 treatment also induced the elevation of GLP‐1R immunoreactivity and protein levels in the ischemic CA1 region. These results indicate that GLP‐1R is altered in the ischemic region after an ischemic insult and that EX‐4 protects against ischemia‐induced neuronal death possibly by increasing GLP‐1R expression and attenuating microglial activation against transient cerebral ischemic damage. © 2011 Wiley‐Liss, Inc.</P>
Bio‐Inspired Complementary Photoconductor by Porphyrin‐Coated Silicon Nanowires
Choi, Sungx2010,Jin,Lee, Youngx2010,Chul,Seol, Myeong‐,Lok,Ahn, Jaex2010,Hyuk,Kim, Sungho,Moon, Dongx2010,Il,Han, Jinx2010,Woo,Mann, Stephen,Yang, Jix2010,Won,Choi, Yangx2010,Kyu WILEY‐VCH Verlag 2011 Advanced Materials Vol.23 No.34
<P><B>A symbiotically bio‐inspired complementary photoconductor</B> is demonstrated using a well‐defined silicon nanowire (SiNW) and porphyrins. The observed direction of the conductance change by light illumination has opposite signs for n‐ and p‐type SiNWs. On the basis of this observation, it is concluded that complementary photoconductors can be used to form functional logic gates of optical input with remarkably low static power dissipation.</P>
Kim, Hyunx2010,Ouk,Kim, Eunjung,An, Yonghee,Choi, Jihye,Jang, Eunji,Choi, Eun Bi,Kukreja, Aastha,Kim, Myeong‐,Hoon,Kang, Byunghoon,Kim, Dongx2010,Joo,Suh, Jinx2010,Suck,Huh, Yongx2010,Mi WILEY‐VCH Verlag 2013 Macromolecular bioscience Vol.13 No.6
<P><B>Abstract</B></P><P>Combined cancer treatment via co‐delivery of siRNAs and an anticancer drug can be a promising strategy due to the synergistic effect of simultaneously minimizing gene/drug administration. In this study, Bcl‐xL siRNA and doxorubicin (DOX) are encapsulated into designed methoxy‐poly(ethylene glycol)‐<I>block</I>‐poly(<SMALL>D</SMALL>,<SMALL>L</SMALL>‐lactic acid) (mPEG‐<I>b</I>‐PLA) block copolymer polymersomes (PSomes). A study of the cytotoxicity of Bcl‐xL siRNA and DOX co‐encapsulated PSomes (CPSomes) shows more inhibited proliferation of MKN‐45 and MKN‐28 human gastric cancer cell lines than only gene‐ and drug‐loaded ones. Consequently, these results demonstrate that co‐delivery of genes and drugs using PSomes results in a synergistic efficacy and indicates the potential of PSomes as efficient nanocarriers for combined cancer therapy. </P>
Chung, Woox2010,Suk,Kim, Myeong‐,Jin,Chung, Yong Eun,Kim, Yeox2010,Eun,Park, Mix2010,Suk,Choi, Jinx2010,Young,Kim, Ki Whang Wiley Subscription Services, Inc., A Wiley Company 2011 JOURNAL OF MAGNETIC RESONANCE IMAGING Vol.34 No.2
<P><B>Abstract</B></P><P><B>Purpose:</B></P><P>To retrospectively compare the diagnostic accuracy for the detection of colorectal liver metastases between gadoxetic acid‐enhanced MRI (EOB‐MRI) and diffusion‐weighted imaging (DWI) on 3.0 Tesla (T) system, and then to determine whether a combination of the two techniques may improve the diagnostic performance.</P><P><B>Materials and Methods:</B></P><P>Forty‐seven patients underwent MR imaging at 3.0T, including DWI (DWI set) and dynamic and hepatobiliary phase EOB‐MRI (EOB set) for the preoperative evaluation of colorectal liver metastases. All suspicious metastases were confirmed by hepatic surgery. Two blinded readers independently reviewed three different image sets, which consisted of DWI set, EOB set, and combined set. The accuracy was assessed by the area (Az) under the alternative‐free response receiver operating characteristic curve, and the sensitivity and positive predictive value (PPV) were calculated.</P><P><B>Results:</B></P><P>We found a total of 78 confirmed colorectal liver metastases in 42 of 47 patients. Each reader noted higher diagnostic accuracy of combined set of EOB‐MRI and DWI than DWI set and EOB set, without statistical significance. Regardless of the size of colorectal liver metastasis, each reader detected significantly more metastases on combined set than on DWI set, and PPV was significantly higher with DWI set than with EOB set or with combined set for one reader.</P><P><B>Conclusion:</B></P><P>EOB‐MRI was more useful for the detection of colorectal liver metastases, while DWI was more useful for their characterization. The combination of EOB‐MRI and DWI showed significantly higher accuracy and sensitivity for the preoperative detection of small colorectal liver metastases than DWI. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.</P>
Jang, Taex2010,Sik,Lee, Eunx2010,Jung,Jo, Jix2010,Hoon,Jeon, Jongx2010,Myeong,Kim, Mix2010,Young,Kim, Hyounx2010,Ee,Koh, Youngx2010,Hag Wiley Subscription Services, Inc., A Wiley Company 2012 JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B Vol.b100 No.2
<P><B>Abstract</B></P><P>Nanofibrous membranes, consisting of a poly(<SMALL>L</SMALL>‐lactic acid) (PLLA)‐silica xerogel hybrid material, were successfully fabricated from a hybrid sol using the electrospinning technique for guided bone regeneration (GBR) application. These hybrid nanofibers exhibited a homogeneous and continuous morphology, with a nano‐sized dispersed silica xerogel phase in the PLLA fiber matrix. The mechanical properties, such as the tensile strength and the elastic modulus, were improved as the silica xerogel content increased up to 40%. All of the hybrid membranes exhibited highly hydrophilic surfaces and good proliferation levels. After culturing for 13 days, the cells that were cultured on the hybrid membranes exhibited a significantly higher ALP activity compared to the pure PLLA membrane. Moreover, the <I>in vivo</I> animal experiments that used the rat calvarial defect model revealed a remarkably improved bone regeneration ability for the hybrid membrane compared to pure PLLA. These results demonstrated the feasibility of these hybrid membranes for efficient GBR. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 100B: 321–330, 2012.</P>
Park, Sang Min,Kim, Jungx2010,Sun,Ko, Youngx2010,Guk,Choi, Donghoon,Hong, Myeong‐,Ki,Jang, Yangsoo,Kang, Woong Chol,Ahn, Taehoon,Kim, Byoungx2010,Keuk,Oh, Seong Jin,Jeon, Dong Woon,Yang, J Wiley Subscription Services, Inc., A Wiley Company 2011 Catheterization and cardiovascular interventions Vol.77 No.1
<P><B>Abstract</B></P><P>Objectives: The aims of this study were to identify the efficacy of optimal stent expansion (OSE) according to the Multicenter Ultrasound Stenting in Coronaries Study (MUSIC Study) criteria in drug‐eluting stent (DES) and compare paclitaxel‐eluting stent (PES) to sirolimus‐eluting stent (SES). Background: Although poststent high‐pressure balloon dilatation is proposed after bare metal stent implantation according to OSE, defined by the criteria of the MUSIC Study, very little data are available in DES. Methods: Two hundred fifty patients (M:F = 149:101; age, 61.5 ± 9.2 years) who underwent 9‐month follow‐up angiography in the Poststent Optimal Stent Expansion Trial (POET) were included in this study. We assessed angiographic in‐stent restenosis (ISR) and neointima volume (NV) using IVUS at 9 months. Results: At 9‐month follow up, there were no significant differences in ISR and NV index (NV/stent length, mm<SUP>2</SUP>) between patients with and without OSE. However, the rate of ISR and NV index were higher in PES [ISR: 18 (13.7%) and 4 (3.4%), <I>P</I> = 0.004; NV index: 1.02 ± 0.99 mm<SUP>2</SUP> and 0.21 ± 0.37, <I>P</I> < 0.001 in PES and SES]. Conclusions: OSE according to the MUSIC Study criteria was not related to ISR and NV in the DES era but PES had a significantly higher ISR rate and NV than SES after poststent high‐pressure balloon dilatation. © 2010 Wiley‐Liss, Inc.</P>
Chemical‐Driven Tissue Removal and Removal Profiles by Atmospheric Plasma Irradiation
Koo, Il Gyo,Moore, Cameron A.,Choi, Myeong Yeol,Kim, Gon Jun,Kim, Paul Y.,Kim, Yoonx2010,Sun,Yu, Zengqi,Collins, George J. WILEY‐VCH Verlag 2011 Plasma Processes and Polymers Vol.8 No.12
<P><B>Abstract</B></P><P>We demonstrate the application of RF‐excited plasma to remove localized regions of ex vivo tissue. While some limited tissue removal occurs when using discharges in rare gases alone, the addition of chemical precursors results in an enhancement of etch depth and etch profile under essentially identical plasma conditions of delivered power, applied voltage, and gas flow. Specifically, the material removal rate in our experiments using different <I>CH</I><SUB>4−<I>x</I></SUB><I>Cl</I><SUB><I>x</I></SUB> additives increased with both (i) the molecular chlorine content (<I>x</I> = 2,3,4) of the selected additive, and (ii) the concentration of haloalkane vapor in the gas stream. We attribute this enhancement to the generation and delivery of chemically reactive radicals from the plasma to the tissue, followed by formation of volatile products (i.e., a chemical, rather than physical or thermal, tissue removal process). In addition we observed that cross‐sectional etch profiles differed with the chosen haloalkane additive chemistries, indicative of corresponding differences in chemistries on profile side‐walls versus bottom walls.</P>
Non‐stick Polymer Coatings for Energy‐based Surgical Devices Employed in Vessel Sealing
Kang, Sung Kil,Kim, Paul Y.,Koo, Il Gyo,Kim, Ho Young,Jung, Jaex2010,Chul,Choi, Myeong Yeol,Lee, Jae Koo,Collins, George J. WILEY‐VCH Verlag 2012 Plasma Processes and Polymers Vol.9 No.4
<P><B>Abstract</B></P><P>Energy‐based surgical devices are widely used to fuse tissues and seal vessels, but tissue adhesion to the instrument complicates the procedure. We deposit a robust non‐stick coating on the jaws of LigaSure<SUP>TM</SUP> tissue fusion devices by employing an atmospheric pressure RF‐driven plasma with hexamethyldisiloxane (HMDSO) entrained in argon carrier gas. The hydrophobicity, surface energy, surface topography, and chemical characteristics of deposited films are characterized by water contact angle measurements, surface energy test pens, atomic force microscopy, and Fourier transform infrared spectroscopy, respectively. We demonstrate significantly reduced tissue adhesion to HMDSO polymer film‐coated instruments during the tissue fusion procedure in comparison with uncoated and chromium nitride‐coated instruments.</P>