Polymer‐Stabilized Chromonic Liquid‐Crystalline Polarizer

Park, Seul&#x2010,Ki,Kim, So&#x2010,Eun,Kim, Dae&#x2010,Yoon,Kang, Shin‐,Woong,Shin, Seunghan,Kuo, Shiao&#x2010,Wei,Hwang, Seok&#x2010,Ho,Lee, Seung Hee,Lee, Myong&#x2010,Hoon,Jeong, Kwang&#x201 WILEY‐VCH Verlag 2011 Advanced functional materials Vol.21 No.11

<P><B>Abstract</B></P><P>Robust coatable polarizer is fabricated by the self‐assembly of lyotropic chromonic liquid crystals and subsequent photo‐polymerizing processes. Their molecular packing structures and optical behaviors are investigated by the combined techniques of microscopy, scattering and spectroscopy. To stabilize the oriented Sunset Yellow FCF (H‐SY) films and to minimize the possible defects generated during and after the coating, acrylic acid (AA) is added to the H‐SY/H<SUB>2</SUB>O solution and photo‐polymerized. Utilizing cross‐polarized optical microscopy, phase behaviors of the H‐SY/H<SUB>2</SUB>O/AA solution are monitored by varying the compositions and temperatures of the solution. Based on the experimental results of two‐dimensional wide angle X‐ray diffraction and selected area electron diffraction, the H‐SY crystalline unit cell is determined to be a monoclinic structure with the dimensions of <I>a</I> = 1.70 nm, <I>b</I> = 1.78 nm, <I>c</I> = 0.68 nm, <I>α</I> = <I>β</I> = 90.0° and <I>γ</I> = 84.5°. The molecular arrangements in the oriented H‐SY films were further confirmed by polarized Fourier‐transform infrared spectroscopy. The polymer‐stabilized H‐SY films show good mechanical and chemical stabilities with a high polarizability. Additionally, patterned polarizers are fabricated by applying a photo‐mask during the photo‐polymerization of AA, which may open new doors for practical applications in electro‐optic devices.</P>

Anti‐inflammatory mechanism of ginsenoside Rh1 in lipopolysaccharide‐stimulated microglia: critical role of the protein kinase A pathway and hemeoxygenase‐1 expression

Jung, Ji&#x2010,Sun,Shin, Jin A.,Park, Eun&#x2010,Mi,Lee, Jung&#x2010,Eun,Kang, Young&#x2010,Sook,Min, Sung&#x2010,Won,Kim, Dong&#x2010,Hyun,Hyun, Jin&#x2010,Won,Shin, Chan&#x2010,Young,Kim, Hee&#x201 Blackwell Publishing Ltd 2010 Journal of Neurochemistry Vol.115 No.6

<P> <I>J. Neurochem.</I> (2010) <B>115,</B> 1668–1680.</P><P><B>Abstract</B></P><P>Microglia activation plays a pivotal role in neurodegenerative diseases, and thus controlling microglial activation has been suggested as a promising therapeutic strategy for neurodegenerative diseases. In the present study, we showed that ginsenoside Rh1 inhibited inducible nitric oxide synthase, cyclooxygenase‐2, and pro‐inflammatory cytokine expression in lipopolysaccharide (LPS)‐stimulated microglia, while Rh1 increased anti‐inflammatory IL‐10 and hemeoxygenase‐1 (HO‐1) expression. Suppression of microglial activation by Rh1 was also observed in the mouse brain following treatment with LPS. Subsequent mechanistic studies revealed that Rh1 inhibited LPS‐induced MAPK phosphorylation and nuclear factor‐κB (NF‐κB)‐mediated transcription without affecting NF‐κB DNA binding. As the increase of pCREB (cAMP responsive element‐binding protein) is known to result in suppression of NF‐κB‐mediated transcription, we examined whether Rh1 increased pCREB levels. As expected, Rh1 increased pCREB, which was shown to be related to the anti‐inflammatory effect of Rh1 because pre‐treatment with protein kinase A inhibitors attenuated the Rh1‐mediated inhibition of nitric oxide production and the up‐regulation of IL‐10 and HO‐1. Furthermore, treatment of HO‐1 shRNA attenuated Rh1‐mediated inhibition of nitric oxide and reactive oxygen species production. Through this study, we have demonstrated that protein kinase A and its downstream effector, HO‐1, play a critical role in the anti‐inflammatory mechanism of Rh1 by modulating pro‐ and anti‐inflammatory molecules in activated microglia.</P>

Nogo‐A expression in oligodendroglial tumors

Jung, Tae&#x2010,Young,Jung, Shin,Lee, Kyung&#x2010,Hwa,Cao, Van Thang,Jin, Shu&#x2010,Guang,Moon, Kyung&#x2010,Sub,Kim, In&#x2010,Young,Kang, Sam&#x2010,Suk,Kim, Hyung&#x2010,Seok,Lee, Min&#x2010,Che Blackwell Publishing Asia 2011 Neuropathology Vol.31 No.1

<P>Nogo‐A belongs to the reticulon protein family and is expressed in the inner and outer loops of myelin sheaths of oligodendrocytes. We analyzed the patterns of Nogo‐A expression in human gliomas in an effort to identify a useful marker for the characterization of oligodendroglial tumors. We determined the expression of Nogo‐A in a panel of 58 astrocytic and oligodendroglial tumors using immunohistochemistry and compared the expression of Nogo‐A with Olig‐2, a recently identified marker for oligodendrogliomas. To localize Nogo‐A expression, immunofluorescent staining was performed using other glial markers (MAP‐2 and GFAP). We also confirmed the overexpression of the Nogo‐A protein in 53 astrocytic and oligodendroglial tumors using Western blot analysis. Based on immunohistochemical analysis, Nogo‐A and Olig‐2 had specificity in the detection of oligodendroglial tumors from astrocytic tumors (<I>P</I> = 0.001). The level of Nogo‐A staining was highly correlated with Olig‐2 (<I>P</I> = 0.001). The sensitivity and specificity of Nogo‐A for oligodendroglial tumors was 86.9% and 57.1%, respectively. Nogo‐A expression overlapped that of other oligodendroglial markers, but with different patterns of expression. Western blot analysis revealed that Nogo‐A is predominantly expressed in 85.7% of oligodendroglioma cells and 93.7% of anaplastic oligodendroglioma cells. Like other oligodendroglial markers, Nogo‐A is highly expressed in oligodendroglial tumors; however, it does not serve as a definite marker specific for oligodendroglial tumors.</P>

Solid Free‐Form Fabrication of Tissue‐Engineering Scaffolds with a Poly(lactic‐co‐glycolic acid) Grafted Hyaluronic Acid Conjugate Encapsulating and Intact Bone Morphogenetic Protein–2/Poly(ethylene glycol) Complex

Park, Jung Kyu,Shim, Jin&#x2010,Hyung,Kang, Kyung Shin,Yeom, Junseok,Jung, Ho Sang,Kim, Jong Young,Lee, Keum Hong,Kim, Tae&#x2010,Ho,Kim, Shin‐,Yoon,Cho, Dong&#x2010,Woo,Hahn, Sei Kwang WILEY‐VCH Verlag 2011 Advanced Functional Materials Vol.21 No.15

<P><B>Abstract</B></P><P>Despite wide applications of bone morphogenetic protein–2 (BMP‐2), there are few methods to incorporate BPM‐2 within polymeric scaffolds while maintaining biological activity. Solid free‐form fabrication (SFF) of tissue‐engineering scaffold is successfully carried out with poly(lactic‐<I>co</I>‐glycolic acid) grafted hyaluronic acid (HA‐PLGA) encapsulating intact BMP‐2/poly(ethylene glycol) (PEG) complex. HA‐PLGA conjugate is synthesized in dimethyl sulfoxide (DMSO) by the conjugation reaction of adipic acid dihydrazide modified HA (HA‐ADH) and PLGA activated with <I>N</I>,<I>N</I>′‐dicyclohexylcarbodiimide (DCC) and <I>N</I>‐hydroxysuccinimide (NHS). BMP‐2 is complexed with PEG, which is encapsulated within the PLGA domain of the HA‐PLGA conjugate by SFF to prepare tissue‐engineering scaffolds. In vitro release tests confirm the sustained release of intact BMP‐2 from the scaffolds for up to a month. After confirmation of the enhanced osteoblast cell growth, and high gene‐expression levels of alkaline phosphatase (ALP), osteocalcin (OC), and osterix (OSX) in the cells, the HA‐PLGA/PEG/BMP‐2 scaffolds are implanted into calvarial bone defects of Sprague Dawley (SD) rats. Microcomputed tomography (μCT) and histological analyses with Masson's trichrome, and hematoxylin and eosin (H&E) staining reveal effective bone regeneration on the scaffolds of HA‐PLGA/PEG/BMP‐2 blends.</P>

Characterization of age‐associated exhausted CD 8 ⁺ T cells defined by increased expression of Tim‐3 and PD ‐1

Lee, Kyoo&#x2010,A,Shin, Kwang&#x2010,Soo,Kim, Ga&#x2010,Young,Song, You Chan,Bae, Eun&#x2010,Ah,Kim, Il&#x2010,Kyu,Koh, Choong&#x2010,Hyun,Kang, Chang&#x2010,Yuil John Wiley and Sons Inc. 2016 Aging Cell Vol.15 No.2

<P><B>Summary</B></P><P>Aging is accompanied by altered T‐cell responses that result in susceptibility to various diseases. Previous findings on the increased expression of inhibitory receptors, such as programmed cell death protein 1 (PD‐1), in the T cells of aged mice emphasize the importance of investigations into the relationship between T‐cell exhaustion and aging‐associated immune dysfunction. In this study, we demonstrate that T‐cell immunoglobulin mucin domain‐3 (Tim‐3), another exhaustion marker, is up‐regulated on aged T cells, especially CD8<SUP>+</SUP> T cells. Tim‐3‐expressing cells also produced PD‐1, but Tim‐3<SUP>+</SUP>PD‐1<SUP>+</SUP>CD8<SUP>+</SUP> T cells had a distinct phenotype that included the expression of CD44 and CD62L, from Tim‐3<SUP>−</SUP>PD‐1<SUP>+</SUP> cells. Tim‐3<SUP>+</SUP>PD‐1<SUP>+</SUP>CD8<SUP>+</SUP> T cells showed more evident properties associated with exhaustion than Tim‐3<SUP>−</SUP>PD‐1<SUP>+</SUP>CD8<SUP>+</SUP> T cells: an exhaustion‐related marker expression profile, proliferative defects following homeostatic or TCR stimulation, and altered production of cytokines. Interestingly, these cells produced a high level of IL‐10 and induced normal CD8<SUP>+</SUP> T cells to produce IL‐10, which might contribute to immune dysregulation in aged mice. The generation of Tim‐3‐expressing CD8<SUP>+</SUP> T cells in aged mice seems to be mediated by encounters with antigens but not by specific infection, based on their high expression of CD49d and their unbiased TCR Vβ usage. In conclusion, we found that a CD8<SUP>+</SUP> T‐cell population with age‐associated exhaustion was distinguishable by its expression of Tim‐3. These results provide clues for understanding the alterations that occur in T‐cell populations with age and for improving dysfunctions related to the aging of the immune system.</P>

Ascochlorin inhibits growth factor‐induced HIF‐1α activation and tumor‐angiogenesis through the suppression of EGFR/ERK/p70S6K signaling pathway in human cervical carcinoma cells

Jeong, Ji&#x2010,Hak,Jeong, Yun&#x2010,Jeong,Cho, Hyun&#x2010,Ji,Shin, Jae&#x2010,Moon,Kang, Jeong&#x2010,Han,Park, Kwan&#x2010,Kyu,Park, Yoon&#x2010,Yub,Chung, Il&#x2010,Kyung,Chang, Hyeun&#x2010,Woo Wiley Subscription Services, Inc., A Wiley Company 2012 Journal of cellular biochemistry Vol.113 No.4

<P><B>Abstract</B></P><P>Ascochlorin, a non‐toxic prenylphenol compound derived from the fungus <I>Ascochyta viciae</I>, has been shown recently to have anti‐cancer effects on various human cancer cells. However, the precise molecular mechanism of this anti‐cancer activity remains to be elucidated. Here, we investigated the effects of ascochlorin on hypoxia‐inducible factor‐1α (HIF‐1α) and vascular endothelial growth factor (VEGF) expression in human epidermoid cervical carcinoma CaSki cells. Ascochlorin inhibited epidermal growth factor (EGF)‐induced HIF‐1α and VEGF expression through multiple potential mechanisms. First, ascochlorin selectively inhibited HIF‐1α expression in response to EGF stimulation, but not in response to hypoxia (1% O<SUB>2</SUB>) or treatment with a transition metal (CoCl<SUB>2</SUB>). Second, ascochlorin inhibited EGF‐induced ERK‐1/2 activation but not AKT activation, both of which play essential roles in EGF‐induced HIF‐1α protein synthesis. Targeted inhibition of epidermal growth factor receptor (EGFR) expression using an EGFR‐specific small interfering RNA (siRNA) diminished HIF‐1α expression, which suggested that ascochlorin inhibits HIF‐1α expression through suppression of EGFR activation. Finally, we showed that ascochlorin functionally abrogates in vivo tumor angiogenesis induced by EGF in a Matrigel plug assay. Our data suggest that ascochlorin inhibits EGF‐mediated induction of HIF‐1α expression in CaSki cells, providing a potentially new avenue of development of anti‐cancer drugs that target tumor angiogenesis. J. Cell. Biochem. 113: 1302–1313, 2012. © 2011 Wiley Periodicals, Inc.</P>

Development of a prognosis‐prediction model incorporating genetic polymorphism with pathologic stage in stage I non‐small cell lung cancer: A multicenter study

Lee, Won Kee,Lee, Shin Yup,Choi, Jin Eun,Seok, Yangki,Lee, Eung Bae,Lee, Hyun Cheol,Kang, Hyo&#x2010,Gyoung,Yoo, Seung Soo,Lee, Myung Hoon,Cho, Sukki,Jheon, Sanghoon,Kim, Young Chul,Oh, In Jae,Na, Koo John WileySons Australia, Ltd 2017 Thoracic cancer Vol.8 No.3

<P><B>Background</B></P><P>This multicenter study was performed to develop a prognosis‐prediction model incorporating genetic polymorphism with pathologic stage for surgically treated non‐small cell lung cancer (NSCLC) patients.</P><P><B>Methods</B></P><P>A replication study including 720 patients and a panel of eight single nucleotide polymorphisms (SNPs), which predicted the prognosis of surgically treated NSCLC in our previous study, was conducted. Using the combined cohort of current and previous studies including 1534 patients, a nomogram for predicting overall survival was made using Cox proportional hazards regression.</P><P><B>Results</B></P><P>Among the eight SNPs, C3 rs2287845, GNB2L1 (alias RACK1), and rs3756585 were significantly associated with overall survival. A nomogram was constructed based on pathologic stage and the genotypes of the two SNPs, and the risk score was calculated for each patient in the combined cohort. Using the prognosis‐prediction model, we categorized patients into low, intermediate, and high‐risk groups, which had greater accuracy in predictive ability (log‐rank statistics = 54.66) than the conventional tumor node metastasis staging (log‐rank statistics = 39.56). Next, we generated a prognosis‐prediction model for stage I to identify a subgroup of potential candidates for adjuvant chemotherapy. Notably, 97 out of 499 stage IB patients were classified as high‐risk patients with a similar prognosis to stage II patients, suggesting the benefit of adjuvant chemotherapy.</P><P><B>Conclusions</B></P><P>This prognosis‐prediction model incorporating genetic polymorphism with pathologic stage may lead to more precise prognostication in surgically resected NSCLC patients. In particular, this model may be useful in selecting a subgroup of stage IB patients who may benefit from adjuvant chemotherapy.</P>

Structure and function of the N‐terminal domain of the human mitochondrial calcium uniporter

Lee, Youngjin,Min, Choon Kee,Kim, Tae Gyun,Song, Hong Ki,Lim, Yunki,Kim, Dongwook,Shin, Kahee,Kang, Moonkyung,Kang, Jung Youn,Youn, Hyung&#x2010,Seop,Lee, Jung&#x2010,Gyu,An, Jun Yop,Park, Kyoung Ryou John Wiley and Sons Inc. 2015 EMBO reports Vol.16 No.10

<P><B>Abstract</B></P><P>The mitochondrial calcium uniporter (MCU) is responsible for mitochondrial calcium uptake and homeostasis. It is also a target for the regulation of cellular anti‐/pro‐apoptosis and necrosis by several oncogenes and tumour suppressors. Herein, we report the crystal structure of the MCU N‐terminal domain (NTD) at a resolution of 1.50 Å in a novel fold and the S92A MCU mutant at 2.75 Å resolution; the residue S92 is a predicted CaMKII phosphorylation site. The assembly of the mitochondrial calcium uniporter complex (uniplex) and the interaction with the MCU regulators such as the mitochondrial calcium uptake‐1 and mitochondrial calcium uptake‐2 proteins (MICU1 and MICU2) are not affected by the deletion of MCU NTD. However, the expression of the S92A mutant or a NTD deletion mutant failed to restore mitochondrial Ca<SUP>2+</SUP> uptake in a stable MCU knockdown HeLa cell line and exerted dominant‐negative effects in the wild‐type MCU‐expressing cell line. These results suggest that the NTD of MCU is essential for the modulation of MCU function, although it does not affect the uniplex formation.</P>

Functional intronic variant of <i>SLC5A10</i> affects <i>DRG2</i> expression and survival outcomes of early‐stage non‐small‐cell lung cancer

Hong, Mi Jeong,Yoo, Seung Soo,Choi, Jin Eun,Kang, Hyo&#x2010,Gyoung,Do, Sook Kyung,Lee, Jang Hyuck,Lee, Won Kee,Lee, Jaehee,Lee, Shin Yup,Cha, Seung Ick,Kim, Chang Ho,Lee, Eung Bae,Cho, Sukki,Jheon, S John Wiley and Sons Inc. 2018 Cancer Science Vol.109 No.12

<P>RegulomeDB is a new tool that can predict the regulatory function of genetic variants. We applied RegulomeDB in selecting putative functional variants and evaluated the relationship between these variants and survival outcomes of surgically resected non‐small‐cell lung cancer. Among the 244 variants studied, 14 were associated with overall survival (<I>P </I><<I> </I>0.05) in the discovery cohort and one variant (rs2257609 C>T) was replicated in the validation cohort. In the combined analysis, rs2257609 C>T was significantly associated with worse overall and disease‐free survival under a dominant model (<I>P </I>=<I> </I>2 × 10<SUP>−5</SUP> and <I>P </I>=<I> </I>0.001, respectively). rs2257609 is located in the <I>SLC5A10</I> intron, but RegulomeDB predicted that this variant affected <I>DRG2</I>, not <I>SLC5A10</I> expression. The expression level of <I>SLC5A10</I> was not different with the rs2257609 genotype. However, <I>DRG2</I> expression was different according to the rs2257609 genotype (<I>P</I><SUB>trend</SUB><SUP> </SUP>= 0.03) and was significantly higher in tumor than in non‐malignant lung tissues (<I>P </I>=<I> </I>1 × 10<SUP>−5</SUP>). Luciferase assay also showed higher promoter activity of <I>DRG2</I> in samples with the rs2257609 T allele (<I>P </I><<I> </I>0.0001). rs2257609 C>T affected <I>DRG2</I> expression and, thus, influenced the prognosis of early‐stage non‐small‐cell lung cancer. This study was approved by the Institutional Review Broad of Kyungpook National University of Hospital (Approval No. KNUMC 2014‐04‐210‐003).</P>

Non‐Volatile Control of 2DEG Conductivity at Oxide Interfaces

Kim, Shin‐,Ik,Kim, Dai&#x2010,Hong,Kim, Yoonjung,Moon, Seon Young,Kang, Min&#x2010,Gyu,Choi, Jong Kwon,Jang, Ho Won,Kim, Seong Keun,Choi, Ji&#x2010,Won,Yoon, Seok&#x2010,Jin,Chang, Hye Jung,Kang WILEY‐VCH Verlag 2013 ADVANCED MATERIALS Vol.25 No.33

<P><B>The functionalization of two‐dimensional electron gas (2DEG) at oxide interfaces</B> can be realized integrating 2DEG with multifunctional oxide overlayers by epitaxial growth. Using a ferroelectric Pb(Zr<SUB>0.2</SUB>Ti<SUB>0.8</SUB>)O<SUB>3</SUB> overlayer on 2DEG (LaAlO<SUB>3</SUB>/SrTiO<SUB>3</SUB>), we demonstrate a model system of the functionalized 2DEG, where electrical conductivity of 2DEG can be reversibly controlled with a large on/off ratio (>1000) in a non‐volatile way by ferroelectric polarization switching.</P>