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Induction of Apoptosis by Ethyl Acetate Fraction of Astragalus membranaceus in Human Non-small Cell Lung Cancer Cells - Apoptosis Induction by Astragalus membranaceus -

  • Park, Hyun-Ji;Park, Shin-Hyung
    • Journal of Pharmacopuncture
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    • v.21 no.4
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    • pp.268-276
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    • 2018
  • Objectives: The purpose of this study is to investigate the anti-cancer effects of different fractions of Astragalus membranaceus (AM) in human non-small cell lung cancer (NSCLC) cells. Methods: We isolated hexane, ethyl acetate, and butanol fractions from crude ethanol extract of AM. The cell death was examined by MTT assay and trypan blue exclusion assay. Apoptosis was detected by DAPI staining, annexin V-PI double staining and cell cycle analysis. The expression of apoptosis-related proteins and mitogen-activated protein kinases (MAPKs) was examined by western blot. Results: Among various fractions of AM, the ethyl acetate fraction of AM (EAM) showed the strongest cytotoxic effect in NSCLC cells. EAM reduced the cell proliferation in a time- and dose-dependent manner in NSCLC cells. In addition, EAM induced the chromatin condensation, and increased the population of sub-G1 phase and annexin V-positive cells in a time-dependent manner, indicating that EAM induced apoptosis in NSCLC cells. Consistently, EAM enhanced the expression of cleaved caspase-8 and -9, and induced the accumulation of cleaved- poly (ADP-ribose) polymerase (PARP). Among MAPK proteins, only ERK was dephosphorylated by EAM, suggesting that ERK might be related with EAM-induced apoptosis. Conclusion: Our results clearly demonstrate that EAM exhibited anti-cancer effects in NSCLC cells by induction of apoptosis. We provide a valuable evidence which suggests that AM could be a desirable therapeutic option for treatment of NSCLC.

Reactive Oxygen Species (ROS) Generation Contributes to the Synergistic Anticancer Effect of Astragalus Membranaceus and Adenophora Triphylla Var. Japonica in H1299 Human Lung Carcinoma Cells (H1299 인체폐암세포주에서 활성산소종 생성에 의한 황기와 사삼의 항암 시너지 작용)

  • Min, Tae Rin;Park, Hyun Ji;Park, Shin Hyung
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.32 no.3
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    • pp.157-164
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    • 2018
  • This study was designed to investigate the mechanism of the synergistic anticancer effect of Astragalus membranaceus (AM) and Adenophora triphylla var. japonica (AT) in H1299 human lung carcinoma cells. A combined treatment of ethanol extract of AM (EAM) and AT (EAT) explosively increased the reactive oxygen species (ROS) generation in H1299 cells compared to the single treatment of each of them. Co-treatment of N-acetyl-L-cysteine (NAC) with EAM and EAT markedly enhanced the cell viability and suppressed apoptosis in H1299 cells, suggesting that ROS generation contributed to the anticancer effect of EAM and EAT. Interestingly, the combined treatment of EAM and EAT down-regulated p-AKT in H1299 cells, which was abrogated by NAC treatment. These results clearly indicated that ROS generation mediated the inactivation of AKT. Co-treatment of LY294002 with EAM and EAT significantly reduced the cell viability at a concentration which EAM and EAT didn't show any cytotoxicity. In addition, the recovery of cell viability by co-treatment of NAC with EAM and EAT was quite reversed by LY294002 treatment, which confirmed that the inactivation of AKT played a pivotal role in ROS-mediated apoptosis. Taken together, our results demonstrated that the synergistic anticancer effect of EAM and EAT was mediated by ROS generation and inactivation of AKT. We provide a valuable preclinical data for the development of more effective combination of AM and AT to treat lung cancer.

Positional symmetry of porion and external auditory meatus in facial asymmetry

  • Choi, Ji Wook;Jung, Seo Yeon;Kim, Hak-Jin;Lee, Sang-Hwy
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.37
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    • pp.33.1-33.9
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    • 2015
  • Background: The porion (Po) is used to construct the Frankfort horizontal (FH) plane for cephalometrics, and the external auditory meatus (EAM) is to transfer and mount the dental model with facebow. The classical assumption is that EAM represents Po by the parallel positioning. However, we are sometimes questioning about the possible positional disparity between Po and EAM, when the occlusal cant or facial midline is different from our clinical understandings. The purpose of this study was to evaluate the positional parallelism of Po and EAM in facial asymmetries, and also to investigate their relationship with the maxillary occlusal cant. Methods: The 67 subjects were classified into three groups. Group I had normal subjects with facial symmetry ($1.05{\pm}0.52mm$ of average chin deviation) with minimal occlusal cant (<1.5 mm). Asymmetry group II-A had no maxillary occlusal cant (average $0.60{\pm}0.36$), while asymmetry group II-B had occlusal cant (average $3.72{\pm}1.47$). The distances of bilateral Po, EAM, and mesiobuccal cusp tips of the maxillary first molars (Mx) from the horizontal orbital plane (Orb) and the coronal plane were measured on the three-dimensional computed tomographic images. Their right and left side distance discrepancies were calculated and statistically compared. Results: EAM was located 10.3 mm below and 2.3 mm anterior to Po in group I. The vertical distances from Po to EAM of both sides were significantly different in group II-B (p=0.001), while other groups were not. Interside discrepancy of the vertical distances from EAM to Mx in group II-B also showed the significant differences, as compared with those from Po to Mx and from Orb to Mx. Conclusions: The subjects with facial asymmetry and prominent maxillary occlusal cant tend to have the symmetric position of Po but asymmetric EAM. Some caution or other measures will be helpful for them to be used during the clinical procedures.

Alternatively activated M2 macrophages increase in early stages of experimental autoimmune myocarditis in Lewis rats

  • Oh, Hanseul;Ahn, Meejung;Matsumoto, Yoh;Shin, Taekyun
    • Korean Journal of Veterinary Research
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    • v.53 no.4
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    • pp.225-230
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    • 2013
  • To better understand the role of macrophages in early stages of experimental autoimmune myocarditis (EAM), we compared the expression of inducible nitric oxide synthase (iNOS) and arginase-1, markers for classically activated M1 and alternatively activated M2 macrophages, respectively, in the hearts of EAM-affected and control rats. Immunohistochemical evidence revealed that both iNOS-positive and arginase 1-positive macrophages were found in EAM lesions, while some cells were co-localized with both markers. This finding suggests that the increased level of arginase-1, which is partly from M2 macrophages, contributes to the modulation of EAM, possibly through the reduction of nitric oxide in the lesion.

Beneficial effects of andrographolide in a rat model of autoimmune myocarditis and its effects on PI3K/Akt pathway

  • Zhang, Qi;Hu, Li-qun;Li, Hong-qi;Wu, Jun;Bian, Na-na;Yan, Guang
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.2
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    • pp.103-111
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    • 2019
  • The study is to investigate effects of andrographolide on experimental autoimmune myocarditis (EAM). Lewis rats were immunized on day 0 with porcine cardiac myosin to establish EAM. The EAM rats were treated with either andrographolide (25, 50, 100 mg/kg/day) or vehicle for 21 days. An antigen-specific splenocytes proliferation assay was performed by using the cells from control rats immunized with cardiac myosin. Survival rates, myocardial pathology and myocardial functional parameters (left ventricle end-diastolic pressure, ${\pm}dP/dt$ and left ventricular internal dimension) of EAM rats received andrographolide were significantly improved. Andrographolide treatment caused an decrease in the infiltration of $CD3^+$ and $CD14^+$ positive cells in myocardial tissue. Moreover, andrographolide treatment caused a reduction in the plasma levels of tumor necrosis factor-alpha, interleukin-17 (IL-17) and myosin-antibody, and an increase in the level of IL-10 in EAM rats. Oral administration of andrographolide resulted in the decreased expression of p-PI3K, p-Akt without any change of PI3K and Akt. Further results indicate andrographolide significantly inhibited myosin-induced proliferation in splenocytes, and this effect was inhibited by co-treatment of SC79 (Akt activator). Our data indicate andrographolide inhibits development of EAM, and this beneficial effect may be due to powerful anti-inflammatory activity and inhibitory effect on PI3K/Akt pathway.

Optimal Cardiac Magnetic Resonance Contrast-Enhanced Timing Robust Angiography (CMR-CENTRA) for the Three-Dimensional Reconstruction of the Bilateral Atria in the Electroanatomic Mapping (EAM) of Atrial Fibrillation

  • Kim, Jun Seong;Oh, Yu-Whan;Shim, Jaemin;Kim, Young-Hoon;Hwang, Sung Ho
    • Investigative Magnetic Resonance Imaging
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    • v.21 no.3
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    • pp.131-138
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    • 2017
  • Purpose: To optimize the timing of scans using cardiac magnetic resonance contrast-enhanced timing robust angiography (CMR-CENTRA) for electroanatomic mapping (EAM) of the right atrium (RA) and left atrium (LA) in patients with atrial fibrillation (AF). Materials and Methods: Fifty patients with AF (38 men; mean age, $59.6{\pm}9.3years$) underwent CMR-CENTRA in preparation for EAM. The CMR-CENTRA data were acquired at five different scan times: 0 seconds, 5 seconds, 10 seconds, 15 seconds, and 20 seconds after an intravenous injection of contrast media. To evaluate the degree of contrast enhancement, right atrial relative contrast (RA-RC) and left atrial relative contrast (LA-RC) on the CMR-CENTRA scans were assessed at each time point. The three-dimensional (3D) reconstruction of the RA and LA for the EAM system was performed using the CMR-CENTRA data. Results: A CMR-CENTRA at a scan time of 10 seconds showed significantly greater LA-RC (P < 0.05) compared with all other scan times. A CMR-CENTRA at a scan time of 15 seconds showed significantly greater RA-RC (P < 0.05) compared with all other scan times. In the 3D reconstruction of the RA, the success rates of CMR-CENTRA at scan times of 10 seconds and 15 seconds were 18% and 100%, respectively. In the 3D reconstruction of the LA, the success rates of CMR-CENTRA at 10- and 15-second scan times were 100%. Conclusion: The CMR-CENTRA data acquired at 15 seconds after the injection of contrast media is appropriate for the preparation of an EAM system that is focused on the RA and LA in patients with AF.

Synergistic Anticancer Effect of Astragalus Membranaceus and Adenophora Triphylla Var. Japonica in H1299 Human Lung Carcinoma Cells (H1299 인체폐암세포주에서 황기와 사삼의 항암 시너지 효과)

  • Lee, Ji Min;Kim, Hong Jae;Choi, Yung Hyun;Chi, Gyoo Yong;Park, Shin Hyung
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.31 no.2
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    • pp.111-117
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    • 2017
  • The anti-cancer effects of Astragalus membranaceus (AM) and Adenophora triphylla var. japonica (AT) have been described. Each of their effects mainly focused on the immunopotentiating and apoptosis inducing-ability in several cancer cell lines. Although the combination of AM and AT is occasionally used in Chinese medicine to treat lung cancers, their synergistic effect has not been proved yet. This study was designed to verify whether AM combined with AT exhibits a synergistic anti-cancer effect in H1299 human lung carcinoma cells. The ethanol extracts of AM (EAM) and AT (EAT) showed only slight cytotoxicity in H1299 cells when treated alone. However, the combination of EAM and EAT markedly suppressed the cell growth measured by MTT assay and trypan blue counting assay. In addition, co-treatment of EAM with EAT significantly reduced the colony-forming ability compared with single treatment of EAM or EAT in H1299 cells. We demonstrated that the synergistic effect of AM and AT was related with apoptosis induction proved by an accumulation of chromatin condensation, annexin V-positive cells, sub-G1 phase population, and cleaved-PARP expression, which were not observed by single treatment of EAM or EAT. In conclusion, the combination of EAM and EAT exhibited superior anti-cancer activity in H1299 cells than single treatment of EAM or EAT. We suggest that EAM combined with EAT might be a novel therapeutic option for lung cancer patients, and provide a reference for the development of more effective combination of Chinese herbs to treat lung cancer.

Fabrication of Large Area Transmission Electro-Absorption Modulator with High Uniformity Backside Etching

  • Lee, Soo Kyung;Na, Byung Hoon;Choi, Hee Ju;Ju, Gun Wu;Jeon, Jin Myeong;Cho, Yong Chul;Park, Yong Hwa;Park, Chang Young;Lee, Yong Tak
    • Proceedings of the Korean Vacuum Society Conference
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    • 2013.08a
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    • pp.220-220
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    • 2013
  • Surface-normal transmission electro-absorption modulator (EAM) are attractive for high-definition (HD) three-dimensional (3D) imaging application due to its features such as small system volume and simple epitaxial structure [1,2]. However, EAM in order to be used for HD 3D imaging system requires uniform modulation performance over large area. To achieve highly uniform modulation performance of EAM at the operating wavelength of 850 nm, it is extremely important to remove the GaAs substrate over large area since GaAs material has high absorption coefficient below 870 nm which corresponds to band-edge energy of GaAs (1.424 eV). In this study, we propose and experimentally demonstrate a transmission EAM in which highly selective backside etching methods which include lapping, dry etching and wet etching is carried out to remove the GaAs substrate for achieving highly uniform modulation performance. First, lapping process on GaAs substrate was carried out for different lapping speeds (5 rpm, 7 rpm, 10 rpm) and the thickness was measured over different areas of surface. For a lapping speed of 5 rpm, a highly uniform surface over a large area ($2{\times}1\;mm^2$) was obtained. Second, optimization of inductive coupled plasma-reactive ion etching (ICP-RIE) was carried out to achieve anisotropy and high etch rate. The dry etching carried out using a gas mixture of SiCl4 and Ar, each having a flow rate of 10 sccm and 40 sccm, respectively with an RF power of 50 W, ICP power of 400 W and chamber pressure of 2 mTorr was the optimum etching condition. Last, the rest of GaAs substrate was successfully removed by highly selective backside wet etching with pH adjusted solution of citric acid and hydrogen peroxide. Citric acid/hydrogen peroxide etching solution having a volume ratio of 5:1 was the best etching condition which provides not only high selectivity of 235:1 between GaAs and AlAs but also good etching profile [3]. The fabricated transmission EAM array have an amplitude modulation of more than 50% at the bias voltage of -9 V and maintains high uniformity of >90% over large area ($2{\times}1\;mm^2$). These results show that the fabricated transmission EAM with substrate removed is an excellent candidate to be used as an optical shutter for HD 3D imaging application.

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Correlation analysis between COVID-19 cases and emergency alerts service (COVID-19 확진자 수와 긴급재난문자 서비스의 상관관계 분석)

  • Ju, Sang-Lim;Kang, Hyunjoo;Oh, Seung-Hee
    • The Journal of the Institute of Internet, Broadcasting and Communication
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    • v.21 no.5
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    • pp.1-9
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    • 2021
  • In Korea, various information related to COVID-19 has been provided to the public through an EAM (Emergency Alert Message) service using CBS (Cell Broadcast Service) technology to respond to COVID-19. In particular, local governments have been actively using the EAM service as a major means of responding to COVID-19. However, since excessive use of EAM service has caused the inconvenience of the people rather than the positive effects, the authority to be able to send EAMs has be limited. In this paper, with the purpose of providing primary data for establishing a plan to properly operate EAMs, we compare and analyze the number of EAMs issued and the incidence rate of COVID-19 cases during the period from 2020 to the present. In addition, the monthly EAM usage and incidence rate of COVID-19 cases are compared in detail and correlation analysis is performed for local governments that have issued many EAMs. We expect that the analysis results of this paper will be used as primary data in establishing strategies for EAM service to counteract the prolonged COVID-19.

A Four-Channel Laser Array with Four 10 Gbps Monolithic EAMs Each Integrated with a DBR Laser

  • Sim, Jae-Sik;Kim, Sung-Bock;Kwon, Yong-Hwan;Baek, Yong-Soon;Ryu, Sang-Wan
    • ETRI Journal
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    • v.28 no.4
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    • pp.533-536
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    • 2006
  • A distributed Bragg reflector (DBR) laser and a high speed electroabsorption modulator (EAM) are integrated on the basis of the selective area growth technique. The typical threshold current is 4 to 6 mA, and the side mode suppression ratio is over 40 dB with single mode operation at 1550 nm. The DBR laser exhibits 2.5 to 3.3 mW fiber output power at a laser gain current of 100 mA, and a modulator bias voltage of 0 V. The 3 dB bandwidth is 13 GHz. A 10 Gbps non-return to zero operation with 12 dB extinction ratio is obtained. A four-channel laser array with 100 GHz wavelength spacing was fabricated and its operation at the designed wavelength was confirmed.

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