DMNQ S-64 Induces Apoptosis via Caspase Activation and Cyclooxygenase-2 Inhibition in Human Nonsmall Lung Cancer Cells

LIM, E.-S.,RHEE, Y.-H.,PARK, M.-K.,SHIM, B.-S.,AHN, K.-S.,KANG, H.,YOO, H.-S.,KIM, S.-H. Wiley (Blackwell Publishing) 2007 Annals of the New York Academy of Sciences Vol.1095 No.1

<P>Shikonin has been reported to induce apoptosis and inhibit angiogenesis in vivo and in vitro. 6-(1-propoxyiminoalkyl)-5,8-dimethoxyoxy 1,4-naphtoquinone S-64 (DMNQ S-64) was synthesized as a shikonin derivative. In this article, the underlying apoptotic mechanism of DMNQ S-64 was examined. DMNQ S-64 exerted cytotoxicity against A549 lung carcinoma cells with IC(50) of 27.3 microM. Apoptotic bodies were observed in DMNQ S-64-treated A549 cells by 4'-6-diamidino-2-phenylindole (DAPI) staining assay. DMNQ S-64 also increased sub-G1 DNA portion in a concentration-dependent manner by flow cytometric analysis. Western blotting has revealed that DMNQ S-64 effectively activates the expression of caspase 8, 9, and 3, cleaves poly (ADP-ribose) polymerase, and increases the ratio of Bax/Bcl-2. Furthermore, cytochrome c was released in a concentration-dependent manner by DMNQ S-64. Similarly, DMNQ S-64 significantly increased caspase 3 activity by enzyme-linked immunosorbent assay (ELISA). It also significantly inhibited the level of prostaglandin E2 (PGE(2)) by ELISA and downregulated the expression of cyclooxygenase-2 (COX-2) in a concentration-dependent manner. Taken together, DMNQ S-64 may exhibit cytotoxicity against A549 cells via caspase activation and COX-2 inhibition.</P>

Comparison of contractile mechanisms of sphingosylphosphorylcholine and sphingosine-1-phosphate in rabbit coronary artery

Choi, S.-K.,Ahn, D.-S.,Lee, Y.-H. Oxford University Press 2009 Cardiovascular research Vol.82 No.2

<P>AIMS: Although stimulation with sphingosylphosphorylcholine (SPC) or sphingosine-1-phosphate (S1P) generally leads to similar vascular responses, the contractile patterns and their underlying signalling mechanisms are often distinct. We investigated the different reliance upon Ca2+-dependent and Ca2+-sensitizing mechanisms of constriction in response to SPC or S1P in coronary arteries. METHODS AND RESULTS: Contractile responses, changes in [Ca2+]i, and phosphorylation of myosin light chain phosphatase-targeting subunit (MYPT1) were measured. SPC induced a concentration-dependent sustained contraction. S1P evoked a rapid rise in force (initial transient), which was followed by a secondary sustained force. In the absence of extracellular Ca2+, the concentration dependency of constriction to SPC was shifted to the right, but with no change in maximum force, whereas S1P-induced contraction was significantly blunted. Cyclopiazonic acid (CPA) significantly decreased the initial transient force induced by S1P. In isolated single cells, S1P markedly increased [Ca2+]i, whereas only a modest elevation was noted with SPC. The S1P-induced elevation of [Ca2+]i was abolished by pre-treatment with CPA and was significantly reduced in the absence of extracellular Ca2+. In beta-escin-permeabilized strips, SPC augmented pCa 6.3-induced force; this was significantly inhibited by fasudil hydrochloride. S1P induced little or no augmentation of pCa 6.3-induced force. In intact arteries, SPC-induced contraction was completely inhibited by fasudil hydrochloride. Fasudil hydrochloride had no effect on the initial transient force induced by S1P but significantly inhibited the secondary sustained force. SPC induced a several-fold increase in Thr696 and Thr853 phosphorylation of MYPT1, but S1P did not affect phosphorylation of MYPT1. CONCLUSION: Our results suggest that constriction of coronary arteries in response to the bioactive lipid S1P or SPC occurs by distinct signalling pathways. Activation of the RhoA/RhoA-associated kinase pathway and subsequent phosphorylation of MYPT1 play a key role in SPC-induced coronary contraction, whereas elevation of [Ca2+]i is crucial for S1P-induced coronary constriction.</P>

Predicting temporal shifts in the spring occurrence of overwintered Scotinophara lurida (Hemiptera: Pentatomidae) and rice phenology in Korea with climate change

Lee, H.,Kang, W. S.,Ahn, M. I.,Cho, K.,Lee, J. H. Springer Science + Business Media 2016 International journal of biometeorology Vol.60 No.1

<P>Climate change could shift the phenology of insects and plants and alter their linkage in space and time. We examined the synchrony of rice and its insect pest, Scotinophara lurida (Burmeister), under the representative concentration pathways (RCP) 8.5 climate change scenario by comparing the mean spring immigration time of overwintered S. lurida with the mean rice transplanting times in Korea. The immigration time of S. lurida was estimated using an overwintered adult flight model. The rice transplanting time of three cultivars (early, medium, and medium-late maturing) was estimated by forecasting the optimal cultivation period using leaf appearance and final leaf number models. A temperature increase significantly advanced the 99 % immigration time of S. lurida from Julian day 192.1 in the 2000s to 178.4 in the 2050s and 163.1 in the 2090s. In contrast, rice transplanting time was significantly delayed in the early-maturing cultivar from day 141.2 in the 2000s to 166.7 in the 2050s and 190.6 in the 2090s, in the medium-maturing cultivar from day 130.6 in the 2000s to 156.6 in the 2050s and 184.7 in the 2090s, and in the medium-late maturing cultivar from day 128.5 in 2000s to 152.9 in the 2050s and 182.3 in the 2090s. These simulation results predict a significant future phenological asynchrony between S. lurida and rice in Korea.</P>

The degree complexity of smooth surfaces of codimension 2

Ahn, J.,Kwak, S.,Song, Y. Academic Press 2012 Journal of symbolic computation Vol.47 No.5

For a given term order, the degree complexity of a projective scheme is defined by the maximal degree of the reduced Grobner basis of its defining saturated ideal in generic coordinates (Bayer and Mumford, 1993). It is well known that the degree complexity with respect to the graded reverse lexicographic order is equal to the Castelnuovo-Mumford regularity (Bayer and Stillman, 1987). However, much less is known if one uses the graded lexicographic order (Ahn, 2008; Conca and Sidman, 2005). In this paper, we study the degree complexity of a smooth irreducible surface in P<SUP>4</SUP> with respect to the graded lexicographic order and its geometric meaning. As in the case of a smooth curve (Ahn, 2008), we expect that this complexity is closely related to the invariants of the double curve of a surface under a generic projection. As results, we prove that except in a few cases, the degree complexity of a smooth surface S of degree d with h<SUP>0</SUP>(I<SUB>S</SUB>(2))<>0 in P<SUP>4</SUP> is given by 2+(degY<SUB>1</SUB>(S)-12)-g(Y<SUB>1</SUB>(S)), where Y<SUB>1</SUB>(S) is a double curve of degree (d-12)-g(S@?H) under a generic projection of S. In particular, this complexity is actually obtained at the monomial x<SUB>0</SUB>x<SUB>1</SUB>x<SUB>3</SUB><SUP>(degY<SUB>1</SUB>(S)-12)-g(Y<SUB>1</SUB>(S))</SUP> where k[x<SUB>0</SUB>,x<SUB>1</SUB>,x<SUB>2</SUB>,x<SUB>3</SUB>,x<SUB>4</SUB>] is a polynomial ring defining P<SUP>4</SUP>. Exceptional cases are a rational normal scroll, a complete intersection surface of (2,2)-type, or a Castelnuovo surface of degree 5 in P<SUP>4</SUP> whose degree complexities are in fact equal to their degrees. This complexity can also be expressed in terms of degrees of defining equations of I<SUB>S</SUB> in the same manner as the result of A. Conca and J. Sidman (Conca and Sidman, 2005). We also provide some illuminating examples of our results via calculations done withMacaulay 2 (Grayson and Stillman, 1997).

S100A2 promoter-driven conditionally replicative adenovirus targets non-small-cell lung carcinoma

Lee, K,Yun, S-T,Yun, C-O,Ahn, B-Y,Jo, E-C Macmillan Publishers Limited 2012 Gene Therapy Vol.19 No.10

S100A2, a member of the S100 family of calcium-binding proteins, has been implicated in carcinogenesis as both a tumor suppressor and stimulator. Here, we characterized promoter activity of S100A2, generated an S100A2 promoter-driven conditionally replicative adenovirus (Ad/SA), and evaluated its anti-tumor activity in vitro and in vivo. Promoter activity of S100A2 was greatly restricted to tumor cells, and the S100A2 promoter bound with typical nuclear targets of epidermal growth factor receptor (EGFR) signaling. EGF-stimulated EGFR phosphorylation induced S100A2 expression and further activated E1A expression of Ad/SA, which was restored by EGFR signal inhibition in a concentration-dependent manner in non-small-cell lung carcinoma (NSCLC). In two EGFR-activated tumor xenograft animal models, Ad/SA exhibited potent anti-tumor activity, whereas cetuximab, an EGFR-targeting anticancer drug, was active transiently or ineffective. Combined treatment with cetuximab or cisplatin plus Ad/SA resulted in enhanced anti-tumor activity. Immunohistochemical analysis of tumor sections showed moderate-to-high grade signals for EGFR and adenovirus, and a reduction in viable cells in Ad/SA-treated tumors. Collectively, these results demonstrate that the S100A2 promoter-driven adenovirus is a potent inhibitor of cancers, and further suggest that S100A2 is a target gene of EGFR signaling pathway in NSCLC.

The microRNA miR-124 inhibits vascular smooth muscle cell proliferation by targeting S100 calcium-binding protein A4 (S100A4)

Choe, N.,Kwon, D. H.,Shin, S.,Kim, Y. S.,Kim, Y. K.,Kim, J.,Ahn, Y.,Eom, G. H.,Kook, H. Elsevier Science B.V., Amsterdam. 2017 FEBS letters Vol.591 No.7

<P>S100 calcium-binding protein A4 (S100A4) induces proliferation and migration of vascular smooth muscle cells (VSMCs). We aimed to find the microRNA regulating S100A4 expression. S100A4 transcripts are abruptly increased in the acute phase of carotid arterial injury 1 day later (at day 1) but gradually decreases at days 7 and 14. Bioinformatics analysis reveals that miR-124 targets S100A4. VSMC survival is attenuated by miR-124 mimic but increased by miR-124 inhibitor. miR-124 decreases immediately after carotid arterial injury but dramatically increases at days 7 and 14. miR-124 inhibitor-induced cell proliferation is blocked by S100A4 siRNA, whereas miR-124-induced cell death is recovered by S100A4. Our findings suggest that miR-124 is a novel regulator of VSMC proliferation and may play a role in the development of neointimal proliferation.</P>

早期破膜에 關한 臨床的 考察

許湘,吳文愛,安東源,申吳永 대한산부인과학회 1972 Obstetrics & Gynecology Science Vol.15 No.7

The circulating sphingosine-1-phosphate level predicts incident fracture in postmenopausal women: a 3.5-year follow-up observation study

Bae, S. J.,Lee, S. H.,Ahn, S. H.,Kim, H. M.,Kim, B. J.,Koh, J. M. Springer Science + Business Media 2016 Osteoporosis International Vol.27 No.8

<P>A high level of circulating sphingosine-1-phosphate (S1P) is associated with a high incidence of osteoporotic fracture and a high rate of an insufficient response to bisphosphonate therapy. Sphingosine-1-phosphate (S1P) is a significant regulator of bone metabolism. Recently, we found that a high plasma S1P level is associated with low bone mineral density (BMD), high levels of bone resorption markers (BRMs), and a high risk of prevalent vertebral fracture in postmenopausal women. We investigated the possibility that S1P is a predictor of incident fracture. A total of 248 postmenopausal women participated in this longitudinal study and were followed up for a mean duration of 3.5 years (untreated [n = 76] or treated with bisphosphonate or hormone replacement therapy [n = 172]). The baseline plasma S1P level and prevalent and incident fracture occurrence were assessed. A high S1P level was significantly associated with a higher rate of prevalent fracture after adjusting for femoral neck (FN) BMD, BRM, and potential confounders (odds ratio = 2.05; 95 % confidence interval [CI] = 1.03-4.00). Incident fractures occurred more frequently in the highest S1P tertile (T3) than in the lower two tertiles (T1-2) after adjusting for confounders, including baseline FN BMD, prevalent fracture, antiosteoporotic medication, annualized changes in FN BMD, BRM, and potential confounders (hazard ratio = 5.52; 95 % CI = 1.04-56.54). Insufficient response to bisphosphonate therapy occurred more frequently in T3 than T1-2 (odds ratio = 4.43; 95 % CI = 1.02-21.25). The plasma S1P level may be a potential predictor of fracture occurrence and an insufficient response to bisphosphonate therapy in postmenopausal women.</P>

Various supercritical carbon dioxide cycle layouts study for molten carbonate fuel cell application

Bae, S.J.,Ahn, Y.,Lee, J.,Lee, J.I. Elsevier Sequoia 2014 Journal of Power Sources Vol.270 No.-

Various supercritical carbon dioxide (S-CO<SUB>2</SUB>) cycles for a power conversion system of a Molten Carbonate Fuel Cell (MCFC) hybrid system are studied in this paper. Re-Compressing Brayton (RCB) cycle, Simple Recuperated Brayton (SRB) cycle and Simple Recuperated Transcritical (SRT) cycle layouts were selected as candidates for this study. In addition, a novel concept of S-CO<SUB>2</SUB> cycle which combines Brayton cycle and Rankine cycle is proposed and intensively studied with other S-CO<SUB>2</SUB> layouts. A parametric study is performed to optimize the total system to be compact and to achieve wider operating range. Performances of each S-CO<SUB>2</SUB> cycle are compared in terms of the thermal efficiency, net electricity of the MCFC hybrid system and approximate total volumes of each S-CO<SUB>2</SUB> cycle. As a result, performance and total physical size of S-CO<SUB>2</SUB> cycle can be better understood for MCFC S-CO<SUB>2</SUB> hybrid system and especially, newly suggested S-CO<SUB>2</SUB> cycle shows some success.

장티푸스 및 살모넬라증 병원체에 대한 역학적 연구

박미선,강연호,안윤형,이복권 국립보건연구원 1998 국립보건원보 Vol.35 No.-