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>

Cold stress causes rapid but differential changes in properties of plasma membrane H⁺-ATPase of camelina and rapeseed

Kim, H.S.,Oh, J.M.,Luan, S.,Carlson, J.E.,Ahn, S.J. G. Fischer 2013 Journal of plant physiology Vol.170 No.9

Camelina (Camelina sativa) and rapeseed (Brassica napus) are well-established oil-seed crops with great promise also for biofuels. Both are cold-tolerant, and camelina is regarded to be especially appropriate for production on marginal lands. We examined physiological and biochemical alterations in both species during cold stress treatment for 3 days and subsequent recovery at the temperature of 25<SUP>o</SUP>C for 0, 0.25, 0.5, 1, 2, 6, and 24h, with particular emphasis on the post-translational regulation of the plasma membrane (PM) H<SUP>+</SUP>-ATPase (EC3.6.3.14). The activity and translation of the PM H<SUP>+</SUP>-ATPase, as well as 14-3-3 proteins, increased after 3 days of cold stress in both species but recovery under normal conditions proceeded differently. The increase in H<SUP>+</SUP>-ATPase activity was the most dramatic in camelina roots after recovery for 2h at 25<SUP>o</SUP>C, followed by decay to background levels within 24h. In rapeseed, the change in H<SUP>+</SUP>-ATPase activity during the recovery period was less pronounced. Furthermore, H<SUP>+</SUP>-pumping increased in both species after 15min recovery, but to twice the level in camelina roots compared to rapeseed. Protein gel blot analysis with phospho-threonine anti-bodies showed that an increase in phosphorylation levels paralleled the increase in H<SUP>+</SUP>-transport rate. Thus our results suggest that cold stress and recovery in camelina and rapeseed are associated with PM H<SUP>+</SUP>-fluxes that may be regulated by specific translational and post-translational modifications.

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 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>

A phase II study of S-1 monotherapy administered for 2 weeks of a 3-week cycle in advanced gastric cancer patients with poor performance status

Jeung, H-C,Rha, S Y,Shin, S J,Ahn, J B,Noh, S H,Roh, J K,Chung, H C Nature Publishing Group 2007 The British journal of cancer Vol.97 No.4

<P>Systemic chemotherapy for gastric cancer is often associated with treatment-related toxicity, which is particularly severe in patients with a poor performance status. In this paper, we describe the first study to evaluate S-1 monotherapy as an option for advanced gastric cancer patients who are not candidates for combination chemotherapy due to poor clinical condition. Fifty-two patients with Eastern Cooperative Oncology Group (ECOG) performance scale 2–3, whose general condition had made use of combination chemotherapy impossible, were enrolled. S-1 was administered to 30 patients as second- or third-line therapy. The initial dose of S-1 was 35 mg m<SUP>−2</SUP>, administered b.i.d for 14 days every 3 weeks. With a median follow-up period of 33 weeks, the median progression-free survival, and overall survival were 11 weeks (95% CI, 8–14) and 33 weeks (95% CI, 19–47), respectively. The overall 1-year survival rate was 29% by intent-to-treat analysis. The overall response rate was 12% (95% CI, 3–21), and the percentage of stable disease was 35%, resulting in the disease control rate of 47% (95% CI, 32–60). Significant drug-related toxicity included grade 3 diarrhoea (14%), anorexia (14%), fatigue (10%), neutropenia (10%), and leucopenia (6%). In conclusion, this study indicated the modest activity of S-1 in gastric cancer patients with poor performance status.</P>

Electrochemical analysis on the growth of oxide formed on stainless steels in molten carbonate at 650 ^oC

Ahn, S.,Oh, K.,Kim, M.,Youn, J.,Jo, K.,Kim, K.,Kwon, H. Pergamon Press ; Elsevier Science Ltd 2014 International journal of hydrogen energy Vol.39 No.23

The oxide growth on stainless steel (SS) 310S and 316L, used as a cathode current collector material of molten carbonate fuel cell (MCFC), were examined in the mixture of 62 mol% Li<SUB>2</SUB>CO<SUB>3</SUB>-38 mol% K<SUB>2</SUB>CO<SUB>3</SUB> at 650 <SUP>o</SUP>C by measuring the change in corrosion potential and potentiodynamic response of the alloys and also in terms of impedance analysis on the alloy|oxide layer|electrolyte system. The corrosion potential of SS 316L was in an active region for 12 h-immersion, whereas that of SS 310S drastically increased after 6 h-immersion due to an active to passive transition. The corrosion rate of the two SSs decreased with immersion due to the growth of protective oxide. However, the decrease in the corrosion rate of SS 310S is much greater than that of SS 316L. The oxide formed on the two SSs was found to be duplex layer, composed of inner Cr enriched oxide and outer Fe enriched oxide. However, the inner Cr enriched layer of 310S is more clearly separated from the outer Fe enriched layer than that of SS 316L due primarily to the higher Cr content in SS 310S. The drastic increase in the corrosion potential of SS 310S after 6 h-immersion is closely associated with the growth of the inner Cr enriched oxide layer. The corrosion resistance of SS depends dominantly on the resistance of the inner Cr enriched oxide that is determined form the impedance analysis on the alloy|oxide layer|electrolyte system. The higher corrosion resistance of SS 310S compared with SS 316L results from the more protective inner Cr enriched oxide layer, as confirmed by its higher resistance associated with the higher Cr content in SS 310S.

Purification and characterization of a novel fibrinolytic α chymotrypsin like serine metalloprotease from the edible mushroom, Lyophyllum shimeji

Moon, S.M.,Kim, J.S.,Kim, H.J.,Choi, M.S.,Park, B.R.,Kim, S.G.,Ahn, H.,Chun, H.S.,Shin, Y.K.,Kim, J.J.,Kim, D.K.,Lee, S.Y.,Seo, Y.W.,Kim, Y.H.,Kim, C.S. Society for Bioscience and Bioengineering, Japan ; 2014 Journal of bioscience and bioengineering Vol.117 No.5

A novel fibrinolytic enzyme was purified from Lyophyllum shimeji, a popular edible mushroom in Asia. The enzyme was purified using combination of anion exchange chromatography on a Mono Q 5/5 column and size exclusion gel filtration chromatography on Superdex 200 100/300 column. This purification protocol resulted 80.9-fold purification of the enzyme and a final yield of 5.7%. The molecular weight of the purified enzyme was estimated to be 21 kDa by SDS-PAGE and size exclusion gel filtration. The N-terminal amino acid sequence was found to be ITFQSASP, which is dissimilar from that of known fibrinolytic enzymes. The purified enzyme was a neutral protease with an optimal reaction pH and temperature of 8.0 and 37<SUP>o</SUP>C, respectively. Enzymatic activity was inhibited by Cu<SUP>2+</SUP> and Co<SUP>2+</SUP>. It was also significantly inhibited by PMSF and TPCK. Furthermore, it was found to exhibit a higher specificity for S-7388, a well-known chymotrypsin chromogenic substrate, indicating chymotrypsin like serine metalloprotease. The relative fibrinolytic activity of 5 μg purified enzyme have two fold more activity than 1 unit/ml of plasmin on fibrin plate. Furthermore, purified enzyme preferentially hydrolyzed the Aα-chain followed by the Bβ- and γ-chain of fibrinogen, which is precursor of fibrin. Therefore, these data suggests that the fibrinolytic enzyme derived from edible mushroom, L. shimeji, might be useful for thrombolytic therapy and preventing thrombotic disease.

麥類의 屬間交雜에 關한 硏究 Ⅰ. 麥種間 相互交雜 및 EACA 處理가 雜種種子 形成에 미치는 影響

C.H. CHO(曺章煥),W.S. AHN(安完植),M.Z. KIM(金文子),K.S. MIN(閔庚洙) 한국육종학회 1977 한국육종학회지 Vol.9 No.1

Inter-generic hybridizations were made among the species T. aestivum, T. durum, H. vulgare and S. cereale using 0.1% concentration of immunosuppressant EACA treatment, The results obtained were as follows; 1. In reciprocal T. aestivum x H. vulgare crosses no viable seed were obtained. The cross T. durum x H. vulgar gave 6 viable seeds. 2. The cross H. vulgare x S. cereale resulted in 9.2% of the, fertilized florets setting seed. However, none had a hybird embryo. The reciprocal gave a 0.12% seed set. 22 seeds were viable from the 31 seeds obtained from this cross. 3. T. aestivum x S. cereale cross resulted in 26.3% of the fertilized florets setting seed. In T. durum x S. cereale crosses, 10.6% of the fertilized florets set seed. 4. A differential response to a 0.1% concentration of EACA was observed. T. aestivum intergeneric crosses showed a 4.8% to a 6.0% higher seed set than did none treated plants. However, H. vulgare plants gave a low seed set than did the none treated plants.

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>

Phase II study of preoperative chemoradiotherapy (CRT) with irinotecan plus S-1 in locally advanced rectal cancer

Shin, S.J.,Kim, N.K.,Keum, K.C.,Kim, H.G.,Im, J.S.,Choi, H.J.,Baik, S.H.,Choen, J.H.,Jeung, H.C.,Rha, S.Y.,Roh, J.K.,Chung, H.C.,Ahn, J.B. Elsevier Science Publishers 2010 Radiotherapy and oncology Vol.95 No.3

Background and purpose: The aim of this study is to evaluate the efficacy and safety of preoperative radiation therapy combined with S-1 and irinotecan (SI) in LARC. Materials and methods: Patients were considered LARC if they had a T3/T4 lesion or node positive. Weekly doses of 40mg/m<SUP>2</SUP> irinotecan were intravenously administered once per week during weeks 1-5 of radiotherapy. S-1 (70mg/m<SUP>2</SUP>) was given from Monday to Friday in all weeks of radiotherapy. 3-D conformal radiotherapy was given at daily fractions of 1.8Gy for 5days for a total dose of 50.4 (45+5.4)Gy. Surgery was performed 4-6weeks following the completion of chemoradiation. Results: Between June 2006 and November 2007, 43 pts were enrolled. The stage was: cT3 24 patients, cT4 6 patients; 28 patients were cN+. Forty-one patients completed the chemoradiation and 42 patients underwent operation: a low anterior resection was performed in 36 patients, a total colectomy in 1 patient, and an abdominal perineal resection in 5 patients. T downstaging was observed in 50%; 23 N+ patients became N- (55%). The complete pathological response was observed in 9 patients (21%). The 3-year locoregional failure rate, distant failure rate, disease-free survival, and overall survival were 9.5%, 18.6%, 72.1%, and 94.3%, respectively. Only three patients experienced G3 diarrhea; one had G3 sepsis and two had septic shock. Hematological toxicity (G3-G4) was observed in five patients. Conclusions: This study demonstrated the efficacy of preoperative CRT with S-1 and irinotecan with 21% of complete response. However, prompt recognition and management of infection is needed to use it in patients with locally advanced rectal cancer.