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Song, Young‐,Jo,Jeong, Hyunx2010,Jeong,Kim, Yux2010,Jin,Lee, Sangx2010,Won,Lee, Jungx2010,Bok,Park, Seungx2010,Yong,Song, Chang‐,Seon,Park, Heex2010,Myung,Choi, Inx2010,Soo Wiley Subscription Services, Inc., A Wiley Company 2010 Journal of Medical Virology Vol.82 No.4
<P><B>Abstract</B></P><P>The hepatitis E virus (HEV) is an emerging zoonotic agent, for which pigs are the most important reservoir. Complete genome sequences of two swine HEV strains, designated swKOR‐1 and swKOR‐2, were determined via RT‐PCR and RACE‐PCR. The strains contained genomes composed of 7,222‐ and 7,221‐bp excluding the poly(A) tails, respectively. The swKOR‐1 and swKOR‐2 strains were classified into subtype 3a of genotype 3 via phylogenetic analysis. These strains formed a distinctive cluster in the phylogenetic tree with human and swine HEVs isolated in the USA and human HEVs isolated in Japan. Anti‐HEV antibodies were identified via ELISA in 8 of 99 (8.1%) cats, whereas, among 115 cattle and 213 dogs, no HEV‐specific antibodies were detected. The conserved RNA‐dependent RNA polymerase (RdRp) gene of HEV could be detected via RT‐PCR in 8.7% of raw oysters collected from coastal regions in Korea. The HEV RNAs detected in oysters were identified as belonging to subtype 3a. The HEV RNAs in oysters most closely resembled that of the swKOR‐2 strain. They also showed a close genetic relationship with the swKOR‐1 strain and the swine and human HEVs isolated in the USA. This is the first report describing the detection in oysters of HEV that may have originated from genotype 3 swine HEV in Korea. Pigs and cats infected with HEV, as well as oysters contaminated with HEV, are potential risk factors for HEV transmission to humans. J. Med. Virol. 82:583–591, 2010. © 2010 Wiley‐Liss, Inc.</P>
Ke, Qingbo,Kim, Ho Soo,Wang, Zhi,Ji, Chang Yoon,Jeong, Jae Cheol,Lee, Haengx2010,Soon,Choi, Young‐,Im,Xu, Bingcheng,Deng, Xiping,Yun, Daex2010,Jin,Kwak, Sangx2010,Soo John Wiley and Sons Inc. 2017 Plant biotechnology journal Vol.15 No.3
<P><B>Summary</B></P><P>The flowering time regulator GIGANTEA (GI) connects networks involved in developmental stage transitions and environmental stress responses in <I>Arabidopsis</I>. However, little is known about the role of GI in growth, development and responses to environmental challenges in the perennial plant poplar. Here, we identified and functionally characterized three <I>GI‐like</I> genes (<I>PagGIa</I>,<I> PagGIb</I> and <I>PagGIc)</I> from poplar (<I>Populus alba × Populus glandulosa</I>). <I>PagGIs</I> are predominantly nuclear localized and their transcripts are rhythmically expressed, with a peak around zeitgeber time 12 under long‐day conditions. Overexpressing <I>PagGIs</I> in wild‐type (WT) <I>Arabidopsis</I> induced early flowering and salt sensitivity, while overexpressing <I>PagGIs</I> in the <I>gi‐2</I> mutant completely or partially rescued its delayed flowering and enhanced salt tolerance phenotypes. Furthermore, the PagGIs‐PagSOS2 complexes inhibited PagSOS2‐regulated phosphorylation of PagSOS1 in the absence of stress, whereas these inhibitions were eliminated due to the degradation of PagGIs under salt stress. Down‐regulation of <I>PagGIs</I> by RNA interference led to vigorous growth, higher biomass and enhanced salt stress tolerance in transgenic poplar plants. Taken together, these results indicate that several functions of <I>Arabidopsis GI</I> are conserved in its poplar orthologues, and they lay the foundation for developing new approaches to producing salt‐tolerant trees for sustainable development on marginal lands worldwide.</P>
Upregulation of AMPK by 4‐O‐methylascochlorin promotes autophagy via the HIF ‐1α expression
Seok, Jix2010,Young,Jeong, Yunx2010,Jeong,Hwang, Soonx2010,Kyung,Kim, Cheorlx2010,Ho,Magae, Junji,Chang, Young‐,Chae John Wiley and Sons Inc. 2018 Journal of cellular and molecular medicine Vol.22 No.12
<P><B>Abstract</B></P><P>4‐O‐methylascochlorin (MAC) is a derivative of ascochlorin, a prenyl‐phenol compound antibiotic isolated from the fungus <I>Ascochyta viciae</I>. MAC induces caspase/poly (ADP‐ribose) polymerase‐mediated apoptosis in leukemia cells. However, the effects of MAC on autophagy in cancer cells and the underlying molecular mechanisms remain unknown. Here, we show that MAC induces autophagy in lung cancer cells. MAC significantly induced the expression of autophagy marker proteins including LC3‐II, Beclin1, and ATG7. MAC promoted AMP‐activated protein kinase (AMPK) phosphorylation and inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and its downstream signalling proteins P70S6K and 4EBP1. The AMPK activator AICAR upregulated LC3‐II expression through the AMPK/mTOR pathway similar to the effects of MAC. MAC‐induced LC3‐II protein expression was slightly reduced in AMPK siRNA transfected cells. MAC upregulated hypoxia‐inducible factor‐1α (HIF‐1α) and BNIP3, which are HIF‐1α‐dependent autophagic proteins. Treatment with CoCl<SUB>2</SUB>, which mimics hypoxia, induced autophagy similar to the effect of MAC. The HIF‐1α inhibitor YC‐1 and HIF‐1α siRNA inhibited the MAC‐induced upregulation of LC3‐II and BNIP3. These results suggest that MAC induces autophagy via the AMPK/mTOR signalling pathway and by upregulating HIF‐1α and BNIP3 protein expression in lung cancer cells.</P>
Lee, Yoox2010,Yong,Lee, Jix2010,Hoon,Cho, Jux2010,Young,Kim, Nax2010,Rae,Nam, Daex2010,Hyun,Choi, Inx2010,Suk,Nam, Ki Tae,Joo, Young‐,Chang WILEY‐VCH Verlag 2013 Advanced functional materials Vol.23 No.32
<P><B>Abstract</B></P><P>It remains a fundamental challenge in the development of stretchable electronics to understand how mechanical strain changes the electrical properties of materials. Although the piezoresistive behavior of poly(3,4‐ethylene‐ dioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) has been observed, its intrinsic origin is not yet fully understood because there are many extrinsic contributing factors and an experimental platform with which to assess such behavior has not been established. Here, systematic analysis shows that the matching Poisson's ratio and elastic modulus between PEDOT:PSS films and their underlying substrates is important in decoupling the factors that affect the material's piezoresistivity, allowing for tunable resistivity. Based on such a fundamental understanding, the conductivity of PEDOT:PSS can be controlled to be invariant and decrease as a function of applied tensile stress. Furthermore, a linear response of the resistivity with respect to mechanical strains of up to 60%, which has never before been realized, is shown. The irreversible conductivity enhancement is primarily caused by the coalescence‐induced growth of conductive PEDOT‐rich cores.</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, Young‐,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>
Cho, Young‐,ra,Lee, Ji Hyeon,Kim, Ji Hye,Lee, Sox2010,Yeon,Yoo, Suna,Jung, Minx2010,kyo,Kim, Su Jung,Yoo, Hyun Ju,Pack, Chang‐,Gi,Rho, Jin Kyung,Son, Jaekyoung John Wiley and Sons Inc. 2018 MOLECULAR ONCOLOGY Vol.12 No.7
<P>Matrine is a natural compound extracted from the herb <I>Sophora flavescens</I> Ait which is widely used in traditional Chinese medicine for treating various diseases. Recently, matrine was reported to have antitumor effects against a variety of cancers without any obvious side effects; however, the molecular mechanisms of its antiproliferative effects on cancer are unclear. Here, we report that matrine inhibits autophagy‐mediated energy metabolism, which is necessary for pancreatic cancer growth. We found that matrine significantly reduces pancreatic cancer growth <I>in vitro</I> and <I>in vivo</I> by insufficiently maintaining mitochondrial metabolic function and energy level. We also found that either pyruvate or α‐ketoglutarate supplementation markedly rescues pancreatic cancer cell growth following matrine treatment. Inhibition of mitochondrial energy production results from matrine‐mediated autophagy inhibition by impairing the function of lysosomal protease. Matrine‐mediated autophagy inhibition requires stat3 downregulation. Furthermore, we found that the antitumor effect of matrine on pancreatic cancer growth depends on the mutation of the KRAS oncogene. Together, our data suggest that matrine can suppress the growth of KRAS‐mutant pancreatic cancer by inhibiting autophagy‐mediated energy metabolism.</P>
Kim, Seix2010,Yong,Jeong, Wonx2010,Ik,Mayr, Christian,Park, Young‐,Seo,Kim, Kwonx2010,Hyeon,Lee, Jeongx2010,Hwan,Moon, Chang‐,Ki,Brü,tting, Wolfgang,Kim, Jangx2010,Joo WILEY‐VCH Verlag 2013 Advanced Functional Materials Vol.23 No.31
<P><B>Abstract</B></P><P>High‐efficiency phosphorescent organic light‐emitting diodes (OLEDs) doped with Ir(ppy)<SUB>2</SUB>(acac) [bis(2‐phenylpyridine)iridium(III)‐acetylacetonate] in an exciplex forming co‐host have been optically analyzed. This emitter has a preferred orientation with the horizontal to vertical dipole ratio of 0.77:0.23 as compared to 0.67:0.33 in the isotropic case. Theoretical analysis based on the orientation factor (<I>Θ</I>, the ratio of the horizontal dipoles to total dipoles) and the photoluminescence quantum yield (<I>q</I><SUB>PL</SUB>) of the emitter predicts that the maximum external quantum efficiency (EQE) of the OLEDs with this emitter is about 30%, which matches very well with the experimental data, indicating that the electrical loss of the OLEDs is negligible and the device structure can be utilized as a platform to demonstrate the validity of optical modeling. Based on the results, the maximum EQE achievable for a certain emitting dye in a host can be predicted by just measuring <I>q</I><SUB>PL</SUB> and <I>Θ</I> in a neat film on glass without the need to fabricate devices, which offers a universal plot of the maximum EQE as a function of <I>q</I><SUB>PL</SUB> and <I>Θ</I>.</P>
Jo, Nam Hyun,Kim, Jung Young,Elx2010,Gamal, Mohammed I.,Choi, Wonx2010,Kyoung,Park, Jinx2010,Hun,Kim, Eun Jung,Cho, Jungx2010,Hyuck,Ha, Hyunx2010,Joon,Choi, Tae Hyun,Oh, Chang‐,Hyun John Wiley Sons, Ltd. 2011 Journal of labelled compounds & radiopharmaceutica Vol.54 No.2
<P><B>Abstract</B></P><P>Synthesis, radiolabelling, and <I>in vitro</I> evaluation of a new <SUP>125</SUP>I‐labelled iodouracil hexitol nucleoside analogue are reported. The target compound was successfully synthesized by an iodination–destannylation method and then purified by reverse phase HPLC. The radiochemical purity of the product was >99% with decay‐corrected yields of 48±3%. <I>In vitro</I> cellular uptake testing was carried out using MCA and MCA‐tk cell lines for comparison of compound 1 with [<SUP>18</SUP>F]FHBG. The newly synthesized compound 1 showed higher accumulation in herpex simplex virus type 1 thymidine kinase (HSV1‐tk) gene expression cell line (MCA‐tk cell line) than in the wild type MCA cell line compared with [<SUP>18</SUP>F]FHBG. The MCA‐tk to MCA cellular uptake ratio for compound 1 was higher than that of [<SUP>18</SUP>F]FHBG from 2 h after incubation. The radioiodine‐labelled compound 1 (I‐125, <I>t</I><SUB>1/2</SUB>=59.37 days) has a longer physical half‐life than F‐18‐(<I>t</I><SUB>1/2</SUB>=110 min) labelled FHBG. Radioiodine‐labelled compound 1 could be used for monitoring gene expression for a long time. The selectivity for MCA‐tk cell line makes compound 1 a promising imaging agent for HSV1‐tk expression. Copyright © 2010 John Wiley & Sons, Ltd.</P>
Cho, Hyunx2010,Ji,Kang, Jeongx2010,Han,Kim, Teoan,Park, Kwangx2010,Kyun,Kim, Cheorlx2010,Ho,Lee, Inx2010,Seon,Min, Kwanx2010,Sik,Magae, Junji,Nakajima, Hiroo,Bae, Young‐,Seuk,Chang, Wiley Subscription Services, Inc., A Wiley Company 2009 Journal of cellular biochemistry Vol.107 No.2
<P><B>Abstract</B></P><P>Fibrosis in glomerulosclerosis causes progressive loss of renal function. Transforming growth factor (TGF)‐β, one of the major profibrotic cytokines, induces the synthesis of plasminogen activator inhibitor (PAI)‐1, a factor that plays a crucial role in the development of fibrosis. Here, we found that an isoprenoid antibiotic, ascofuranone, suppresses expression of profibrotic factors including matrix proteins and PAI‐1 induced by TGF‐β in renal fibroblasts. Ascofuranone selectively inhibits phosphorylation of epidermal growth factor receptor (EGFR), and downstream kinases such as Raf‐1, MEK‐1/2, and ERK‐1/2. PAI‐1 transcription also is suppressed by treatment with kinase inhibitors for MEK‐1/2 or EGFR, and with small interfering RNA for EGFR. Ascofuranone inhibits cellular metalloproteinase activity, and an inhibitor of metalloproteinases suppresses EGFR phosphorylation and PAI‐1 transcription. These results suggest that ascofuranone suppresses expression of profibrotic factors through the inhibition of an EGFR‐dependent signal transduction pathway activated by metalloproteinases. J. Cell. Biochem. 107: 335–344, 2009. © 2009 Wiley‐Liss, Inc.</P>
Lee, Sungx2010,Eun,Park, Sung Soo,Jeon, Young‐,Woo,Yoon, Jaex2010,Ho,Cho, Byungx2010,Sik,Eom, Kix2010,Seong,Kim, Yoox2010,Jin,Lee, Seok,Min, Chang‐,Ki,Kim, Heex2010,Je,Cho, Seo John Wiley Sons, Inc. 2018 American journal of hematology Vol.93 No.11
<P><B>Abstract</B></P><P>This prospective study explored an optimal conditioning regimen to ensure engraftment with minimal toxicity in adult patients with severe aplastic anemia (SAA) who received haplo‐identical stem cell transplantation from a related mismatched donor (Haplo‐SCT). We explored a safe and sufficient dose of rabbit ATG (Thymoglobulin) in combination with 800 cGy total body irradiation (TBI) and fludarabine (Flu, 30 mg/m<SUP>2</SUP>/day) for 5 days using step‐by‐step dose de‐escalation. The dose of ATG was de‐escalated from 10 mg/kg (group 1), to 7.5 mg/kg (group 2), to 5 mg/kg (group 3), and the TBI dose was reduced to 600 cGy (group 4) beginning in October 2014. If one patient developed transplant‐related mortality (TRM) with engraftment in a group, we moved to the next lower dose group. Thirty‐four patients were enrolled in groups 1‐3 (<I>n</I> = 10) and 4 (<I>n</I> = 24). All patients achieved primary engraftment. The incidence of acute GVHD (grade ≥ 2) and chronic GVHD (≥ moderate) was 29.4% and 14.7%, respectively. With a median follow‐up of 56.6 and 21.8 months in groups 1‐3 and group 4, respectively, the 2‐year probability of overall survival (91.7% in group 4 vs 70% in groups 1‐3, <I>P</I> = 0.155) and GVHD‐free survival (78.4% in group 4 vs 50% in groups 1‐3, <I>P</I> = 0.115) was shown tended to be better in group 4. This study explored an optimal conditioning with step‐by‐step de‐escalation dosage of ATG and TBI to reduce TRM with sustained graft function. TBI‐600 cGy/Flu/intermediate‐dose ATG resulted in feasible outcomes of Haplo‐SCT for adult patients with SAA.</P>