Implication of intracellular ROS formation, caspase-3 activation and Egr-1 induction in platycodon D-induced apoptosis of U937 human leukemia cells

Shin, D.Y.,Kim, G.Y.,Li, W.,Choi, B.T.,Kim, N.D.,Kang, H.S.,Choi, Y.H. Masson Pub. USA, Inc 2009 BIOMEDICINE AND PHARMACOTHERAPY Vol.63 No.2

Platycodon D is a major constituent of triterpene saponins found in the root of Platycodon grandiflorum, Platycodi Radix, which is widely used in traditional Oriental medicine for the treatment of many chronic inflammatory diseases. The results of previous studies have shown that this compound has in vitro growth-inhibitory activity in human cancer cells, however, the mechanism by which this action occurs is poorly understood. In this study, we examined the effects of platycodon D on the production of reactive oxygen species (ROS) and evaluated the association of these effects with apoptotic tumor cell death using a human leukemic U937 cell line. The results of this study demonstrate that platycodon D mediates ROS production, and that this mediation is followed by a decrease in mitochondrial membrane potential (MMP, ΔΨ<SUB>m</SUB>), activation of caspase-3, and cleavage of poly (ADP-ribose) polymerase (PARP). Both the cytotoxic effects and apoptotic characteristics induced by platycodon D treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrates the important role that caspase-3 plays in the observed cytotoxic effect. Additionally, the transcription factor early growth response-1 (Egr-1) gene was transcriptionally activated and the levels of non-steroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1) protein were elevated in platycodon D-treated U937 cells. However, the quenching of ROS generation in response to treatment with a ROS scavenger, N-acetyl-l-cysteine, reversed the platycodon D-induced apoptosis effects via inhibition of Egr-1 activation, ROS production, MMP collapse, and the subsequent activation of caspase-3. Although further studies are needed to demonstrate that increased expression of Egr-1 by platycodon D leads directly to NAG-1 induction and subsequent apoptosis, our observations clearly indicate that ROS induced through Egr-1 activation are involved in the early molecular events involved in the platycodon D-induced apoptotic pathway.

Aberrant ventral striatal responses during incentive processing in unmedicated patients with obsessive–compulsive disorder

Jung, W. H.,Kang, D.‐,H.,Han, J. Y.,Jang, J. H.,Gu, B.‐,M.,Choi, J.‐,S.,Jung, M. H.,Choi, C.‐,H.,Kwon, J. S. Blackwell Publishing Ltd 2011 Acta psychiatrica Scandinavica Vol.123 No.5

<P>Jung WH, Kang D‐H, Han JY, Jang JH, Gu B‐M, Choi J‐S, Jung MH, Choi C‐H, Kwon JS. Aberrant ventral striatal responses during incentive processing in unmedicated patients with obsessive–compulsive disorder.</P><P><B>Objective: </B> Obsessive–compulsive disorder (OCD) is characterized by the dysfunction of control and reward mechanisms. However, only few neuroimaging studies of OCD have examined the reward processing. We examined the neural responses during incentive processing in OCD.</P><P><B>Method: </B> Twenty unmedicated patients with OCD and 20 age‐, sex‐, and IQ‐matched healthy controls underwent functional magnetic resonance imaging while performing a modified monetary incentive delay task.</P><P><B>Results: </B> Compared with controls, patients with OCD showed increased ventral striatal activation in the no‐loss minus loss outcome contrast and a significant positive correlation between the ventral striatal activation and compulsion symptom severity. In addition, patients with OCD showed increased activations in the frontostriatal regions in the gain minus no‐gain outcomes contrast. During loss anticipation, patients with OCD showed less activations in the lateral prefrontal and inferior parietal cortices. However, during gain anticipation, patients with OCD and healthy controls did not differ in the ventral striatal activation.</P><P><B>Conclusion: </B> These findings provide neural evidence for altered incentive processing in unmedicated patients with OCD, suggesting an elevated sensitivity to negatively affect stimuli as well as dysfunction of the ventral striatum.</P>

HIV env 유전자의 V1-V5 부위 분석에 의한 HIV 분리주의 subtype 및 변이 분석

김성순,강춘,박근용,남정구,최병선,기미경,서순덕,이성래,이주실 국립보건연구원 1999 국립보건원보 Vol.36 No.-

Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis

Yu, K‐,H.,Hong, K‐,S.,Lee, B‐,C.,Oh, M‐,S.,Cho, Y‐,J.,Koo, J‐,S.,Park, J‐,M.,Bae, H‐,J.,Han, M‐,K.,Ju, Y‐,S.,Kang, D‐,W.,Appelros, P. Blackwell Publishing Ltd 2011 Acta neurologica Scandinavica Vol.123 No.5

<P>Yu K‐H, Hong K‐S, Lee B‐C, Oh M‐S, Cho Y‐J, Koo J‐S, Park J‐M, Bae H‐J, Han M‐K, Ju Y‐S, Kang D‐W, Appelros P, Norrving B, Terent A. Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis. 
Acta Neurol Scand: 2011: 123: 325–331. 
© 2010 John Wiley & Sons A/S.</P><P><B>Background – </B> It has not been clarified whether the disparity in ischemic stroke outcome between populations is caused by ethnic and geographic differences or by variations in case mix. Propensity score matching (PSM) analysis can overcome some analytical problems but is rarely used in stroke outcome research. This study was to compare the ischemic stroke case‐fatality between two PSM cohorts of Sweden and Korea.</P><P><B>Methods – </B> Prognostic variables related to baseline characteristics and stroke care were included in our PSM model. Then, we selected 7675 Swedish and 1220 Korean patients with ischemic stroke from each stroke registers and performed one‐to‐one matching based on propensity scores of each patient.</P><P><B>Results – </B> After PSM, all measured variables were well balanced in 1163 matched subjects, and the 90‐day case‐fatality was identical 6.2% (HR 0.997, 95%CI 0.905–1.099) in Sweden and Korea.</P><P><B>Conclusions – </B> No difference is found in the 90‐day case‐fatality in propensity score‐matched Swedish and Korean patients with ischemic stroke.</P>

Study on the HDDR Characteristics of the Nd-Fe(-Co)-B(-Ga-Zr)-type Alloys

S. W. Shon,H. W. Kwon,D. I. Kang,Yoon. B. Kim,W. Y. Jeung 한국자기학회 1999 Journal of Magnetics Vol.4 No.4

The HDDR characteristics of the Nd-Fe-B-type isotropic and anisotropic HDDR alloys were investigated using three types of alloys: alloy A (Nd_(12.6)Fe_(81.4)B_6), alloy B (Nd_(l2.6)Fe_(81.3)B_6Zr_(0.l)), and alloy C (Nd_(12.6)Fe_(68.8)CO_(11.5)B_6Ga_(1.0)Zr_(0.1)). The alloy A is featured with the isotropic HDDR character, while alloy Band C are featured with the anisotropic HDDR character. Hydrogenation and disproportionation characteristics of the alloys were examined using DTA under hydrogen gas. Recombination characteristics of the alloys were examined by observing the coercivity variation as a function of recombination time. The present study revealed that the alloy C exhibits slightly higher hydrogenation and disproportionation temperatures compared to the alloy A and B. Recombination of the anisotropic alloy Band C takes place more rapidly with respect to the isotropic alloy A. The intrinsic coercivities of the recombined materials rapidly increased with increasing the recombination time and then showed a peak, after which the coercivities decreased gradually. The degraded coercivity was, however, recovered significantly on prolonged recombination treatment. Compared with the isotropic HDDR alloy A the anisotropic HDDR alloy B and C are notable for their greater recovery of coercivity. The significant recovery of coercivity was accounted for in terms of the development of well-defined smooth grain boundary between the recombined grains on prolonged recombination.

IL-32γ inhibits cancer cell growth through inactivation of NF-κB and STAT3 signals

Oh, J H,Cho, M-C,Kim, J-H,Lee, S Y,Kim, H J,Park, E S,Ban, J O,Kang, J-W,Lee, D-H,Shim, J-H,Han, S B,Moon, D C,Park, Y H,Yu, D-Y,Kim, J-M,Kim, S H,Yoon, D-Y,Hong, J T Nature Publishing Group 2011 Oncogene Vol.30 No.30

<P>Several studies have shown physiological functions of interleukin (IL)-32, a novel cytokine. However, the role of IL-32 in cancer development has not been reported. In this study, we showed that IL-32γ inhibited tumor growth in IL-32γ-overexpressing transgenic mice inoculated with melanoma as well as colon tumor growth in xenograft nude mice inoculated with IL-32γ-transfected colon cancer cells (SW620). The inhibitory effect of IL-32γ on tumor growth was associated with the inhibition of constitutive activated nuclear transcription factor-κB (NF-κB) and of signal transducer and activator of transcription 3 (STAT3). The expression of antiapoptotic, cell proliferation and tumor-promoting genes (<I>bcl-2</I>, <I>X-chromosome inhibitor of apoptosis protein</I> (<I>IAP</I>), <I>cellular IAP</I> and <I>cellular FADD-like IL-1β-converting enzyme-inhibitory protein</I>, <I>cyclin D</I>), cyclin-dependent kinase 4, cycolooxygenase-2 and inducible nitric oxide synthase was decreased, whereas the expression of apoptotic target genes (<I>caspase-3</I> and <I>-9</I>, <I>bax</I>) increased. In tumor, spleen and blood, the number of cytotoxic CD8<SUP>+</SUP> T cells and CD57<SUP>+</SUP> natural killer cells and the levels of IL-10 increased, but that of tumor necrosis factor-α (TNF-α), IL-1β and IL-6 decreased. We also found that forced overexpression of IL-32γ inhibited colon cancer cell (SW620 and HCT116) growth accompanied with the inhibition of activated NF-κB and STAT3 <I>in vitro</I>. In addition, when IL-32γ was knocked down by small interfering RNA (siRNA) or neutralized with an anti-IL-32γ antibody, IL-32γ-induced colon cancer cell growth inhibition, the IL-32γ-induced decrease of TNF-α, IL-1 and IL-6 production, and the increase of IL-10 production were abolished. However, siRNA of NF-κB and STAT3 augmented IL-32γ-induced colon cancer cell growth inhibition. These findings indicate significant pathophysiological roles of IL-32γ in cancer development.</P>

TFAP2C promotes lung tumorigenesis and aggressiveness through miR-183- and miR-33a-mediated cell cycle regulation

Kang, J,Kim, W,Lee, S,Kwon, D,Chun, J,Son, B,Kim, E,Lee, J-M,Youn, H,Youn, B Macmillan Publishers Limited, part of Springer Nat 2017 Oncogene Vol.36 No.11

<P>Non-small cell lung cancer (NSCLC) remains one of the leading causes of death worldwide, and thus new molecular targets need to be identified to improve treatment efficacy. Although epidermal growth factor receptor (EGFR)/KRAS mutation-driven lung tumorigenesis is well understood, the mechanism of EGFR/KRAS-independent signal activation remains elusive. Enhanced TFAP2C (transcription factor activating enhancer-binding protein 2C) expression is associated with poor prognosis in some types of cancer patients, but little is known of its relation with the pathogenesis of lung cancer. In the present study, we found that TFAP2C overexpression was associated with cell cycle activation and NSCLC cell tumorigenesis. Interestingly, TFAP2C blocked AKAP12mediated cyclin D1 inhibition by inducing the overexpression of oncogenic microRNA (miRNA)-183 and simultaneously activated cyclin-dependent kinase 6-mediated cell cycle progression by downregulating tumor-suppressive miRNA-33a. In a mouse xenograft model, TFAP2C promoted lung tumorigenesis and disease aggressiveness via the miR-183 and miR-33a pathways. The study provides a mechanism of mitogenic and oncogenic signaling via two functionally opposed miRNAs and suggests that TFAP2Cinduced cell cycle hyperactivation contributes to lung tumorigenesis.</P>

Mitochondria-targeted fluorescent carbon nano-platform for NIR-triggered hyperthermia and mitochondrial inhibition

Kang, E.B.,In, I.,Lee, K.D.,Park, S.Y. THE KOREAN SOCIETY OF INDUSTRIAL AND ENGINEERING 2017 JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY -S Vol.55 No.-

<P>We report mitochondria-targeted photothermal nanoparticles with the blocker 3-bromopyruvate (BP), delocalized lipophilic triphenylphosphonium (TPP) cations to target them to the mitochondrial membrane, and folic acid (FA) to target cancer cells. The carbonized polyethylene glycol grafted poly (dimethyl aminoethyl methacrylate)-q-catechol (F-PEG-g-PDMA-CCDP) was crosslinked with boronic acid-grafted polyethylene glycol-g-poly (dimethyl aminoethyl methacrylate) conjugated with IR825 as a near-infrared (NIR) responsive fluorescent agent, FA, TPP, BP (PEG-g-PDMA-FA/IR/TPP/BP). The F-PEG-g-PDMA-CCDP@PEG-g-PDMA-FA/IR/TPP/BP (F-FNP) showed in vitro anticancer activity to normal and cancer cell under NIR light treatments. The blocking of metabolic activity in mitochondria with a photothermal system might represent a new pathway for cancer therapy. (C) 2017 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.</P>

MAGNETIC PROPERTIES OF NANOCRYSTALLINE (Fe, Co) - B - Al - M (M=Nb / Mo / Ta) ALLOYS

D. B. Kang,W. S. Cho,T. K. Kim,Y. S. Cho 한국자기학회 1995 韓國磁氣學會誌 Vol.5 No.5

Soft magnetic properties of Fe-based (Fe, Co)-B-Al-M (M=Nb, Mo or Ta) nanocrystalline alloy have been investigated. The alloy obtained directly from the rapid solidification process. Microstructure of the alloy is a mixture of ultrafine bcc Fe(Co) nanocrystallines and a small amount of retained amorphous phase. Heat treatment of as-prepared alloys improves soft magnetic properties in high frequency range. (Fe._(85)Co._(15))_(70)B_(18)Al_(10)Ta_6 alloy annealed at 500℃ for 1 h shows the most improved soft magnetic properties among the alloys examined. Average grain size of the nanocrystalline is about 10 ㎚.

Possible origin of stabilized monoclinic structure of KNbO₃ nanomaterials at room temperature

Kang, P.G.,Yun, B.K.,Shin, S.,Ko, J.H.,Lee, D.J.,Lee, Y.S.,Jung, J.H. Elsevier 2016 Materials science and engineering B. Advanced Func Vol.210 No.-

<P>We have investigated the structural phase transition and phase stability of newly discovered monoclinic crystal structure of KNbO3 nanomaterials. Through x-ray diffraction, Raman scattering, and neutron diffraction measurements, we have found that the KNbO3 grown at low temperature undergoes a successive structural transition from monoclinic, tetragonal, to cubic, while the KNbO3 grown at high temperature does from monoclinic, orthorhombic, tetragonal, to cubic with the increase of temperature. After heat treatment, the monoclinic structure of KNbO3 is transformed to an orthorhombic structure at room temperature. Accompanying the structural transformation, the Raman peaks corresponding to surface and lattice hydroxyl groups are strongly suppressed. These results imply that the hydroxyl defects should play a crucial role for the monoclinic structure of KNbO3 at room temperature. (C) 2016 Elsevier B.V. All rights reserved.</P>