• Title/Summary/Keyword: Pi-b

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Analysis of Cholangitis Rates with Extended Perioperative Antibiotics and Adjuvant Corticosteroids in Biliary Atresia

  • Goh, Lynette;Phua, Kong Boo;Low, Yee;Chiang, Li Wei;Yong, Chen;Chiou, Fang Kuan
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.24 no.4
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    • pp.366-376
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    • 2021
  • Purpose: There is no consensus regarding adjuvant therapies following Kasai portoenterostomy (KP) for biliary atresia (BA). This study aimed to analyze the effect of extended perioperative intravenous antibiotics (PI-Abx) and adjuvant corticosteroid on cholangitis and jaundice clearance rates in the 3 years post-KP in children with BA. Methods: Data of patients who underwent KP between 1999-2018 at a single center were retrospectively analyzed. Group A (1999-2010) received PI-Abx for 5 days, Group B (2010-2012) received PI-Abx for 5 days plus low-dose prednisolone (2 mg/kg), and Group C (2012-2017) received PI-Abx for 14 days plus high-dose prednisolone (5 mg/kg). Results: Fifty-four patients were included with groups A, B, and C comprising 25, 9, and 20 patients, respectively. The number of episodes of cholangitis was 1.0, 1.6, and 1.3 per patient (p=NS) within the first year and 1.8, 2.3, and 1.7 (p=NS) over 3 years in Groups A, B, and C, respectively. The jaundice clearance rate at 6 months was 52%, 78%, and 50% (p=NS), and the 3-year native liver survival (NLS) rate was 76%, 100%, and 80% (p=NS) in Groups A, B, and C, respectively. A near-significant association was observed between the incidence of cholangitis within the first year and decompensated liver cirrhosis/death at 3 years post KP (p=0.09). Persistence of jaundice at 6 months was significantly associated with decompensated cirrhosis/death at 3 years (p<0.001). Conclusion: The extended duration of PI-Abx and adjuvant corticosteroids was not associated with improved rates of cholangitis, jaundice clearance, or NLS in patients with BA.

Inhibition of DNMT3B and PI3K/AKT/mTOR and ERK Pathways as a Novel Mechanism of Volasertib on Hypomethylating Agent-Resistant Cells

  • Eun-Ji Choi;Bon-Kwan Koo;Eun-Hye Hur;Ju Hyun Moon;Ji Yun Kim;Han-Seung Park;Yunsuk Choi;Kyoo-Hyung Lee;Jung-Hee Lee;Eun Kyung Choi;Je-Hwan Lee
    • Biomolecules & Therapeutics
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    • v.31 no.3
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    • pp.319-329
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    • 2023
  • Resistance to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is a concerning problem. Polo-like kinase 1 (PLK1) is a key cell cycle modulator and is known to be associated with an activation of the PI3K pathway, which is related to the stabilization of DNA methyltransferase 1 (DNMT1), a target of HMAs. We investigated the effects of volasertib on HMA-resistant cell lines (MOLM/AZA-1 and MOLM/DEC-5) derived from MOLM-13, and bone marrow (BM) samples obtained from patients with MDS (BM blasts >5%) or AML evolved from MDS (MDS/AML). Volasertib effectively inhibited the proliferation of HMA-resistant cells with suppression of DNMTs and PI3K/AKT/mTOR and ERK pathways. Volasertib also showed significant inhibitory effects against primary BM cells from patients with MDS or MDS/AML, and the effects of volasertib inversely correlated with DNMT3B expression. The DNMT3B-overexpressed AML cells showed primary resistance to volasertib treatment. Our data suggest that volasertib has a potential role in overcoming HMA resistance in patients with MDS and MDS/AML by suppressing the expression of DNMT3 enzymes and PI3K/AKT/mTOR and ERK pathways. We also found that DNMT3B overexpression might be associated with resistance to volasertib.

Auranofin accelerates spermidine-induced apoptosis via reactive oxygen species generation and suppression of PI3K/Akt signaling pathway in hepatocellular carcinoma

  • Hyun Hwangbo;Da Hye Kim;Min Yeong Kim;Seon Yeong Ji;EunJin Bang;Su Hyun Hong;Yung Hyun Choi;JaeHun Cheong
    • Fisheries and Aquatic Sciences
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    • v.26 no.2
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    • pp.133-144
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    • 2023
  • Auranofin is a US Food and Drug Administration (FDA)-approved anti-arthritis medication that functions as a thioredoxin reductase inhibitor. Spermidine, a polyamine present in marine algae, can exert various physiological functions. Herein, we examined the synergistic anticancer activity of auranofin and spermidine in hepatocellular carcinoma (HCC). Combined treatment with auranofin and spermidine suppressed cell viability more efficiently than either treatment alone in HCC Hep3B cells. The isobologram plotted by calculating the half maximal inhibitory concentration (IC50) values of each drug indicated that the two drugs exhibited a synergistic effect. Based on the analysis of annexin V and cell cycle distribution, auranofin and spermidine markedly induced apoptosis in Hep3B cells. Moreover, auranofin and spermidine increased mitochondria-mediated apoptosis by promoting mitochondrial membrane potential (Δψm) loss. Auranofin and spermidine significantly increased reactive oxygen species (ROS) production in Hep3B cells, and the blocking ROS suppressed apoptosis induced by spermidine and auranofin. In addition, auranofin and spermidine reduced the expression of phosphorylated phosphatidylinositol-3 kinase (PI3K) and protein kinase B (Akt), and PI3K inhibitor accelerated auranofin- and spermidine-induced apoptosis. Using ROS scavenger and PI3K inhibitor, we revealed that ROS acts upstream of auranofin- and spermidine-induced apoptosis. Collectively, our study suggests that combination treatment with auranofin and spermidine could afford synergistic anticancer activity via ROS overproduction and reduced PI3K/Akt signaling pathway.

Excited States of Photoreceptor Molecules (I). Peridinin (광합성 에너지 수용색소 분자의 Excited States (第1報) Peridinin)

  • Pill-Soon Song;Tae Young Lee
    • Journal of the Korean Chemical Society
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    • v.23 no.5
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    • pp.314-319
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    • 1979
  • The electronic spectrum of marine dinoflagellate antenna pigment, peridinin, has been described in terms of PPP SCF MO CI computations and fluorescence polarization of the peridinin component in photosynthetic pigment complex of Amphidinium carterae. The main absorption band at 470 nm, $^1B{\leftarrow}A$, is polarized nearly along the long molecular axis. There appear to be two ${\pi}{\rightarrow}{\pi}^*$ transitions (C and $D{\leftarrow}A$) in the socalled "cis" peak region, and they are polarized roughly parallel to the main $B{\leftarrow}A$ absorption. In addition, we have found that the carbonyl group undergoes very 1ittle reorganization of the electronic structure in going from the ground to the $^1B$ excited states of peridinin, while the allenic group shows a strong charge transfer tendency in producing an electron-deficient allente allene group in the excited state.

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Luteolin and luteolin-7-O-glucoside inhibit lipopolysaccharide-induced inflammatory responses through modulation of NF-${\kappa}B$/AP-1/PI3K-Akt signaling cascades in RAW 264.7 cells

  • Park, Chung Mu;Song, Young-Sun
    • Nutrition Research and Practice
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    • v.7 no.6
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    • pp.423-429
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    • 2013
  • Luteolin is a flavonoid found in abundance in celery, green pepper, and dandelions. Previous studies have shown that luteolin is an anti-inflammatory and anti-oxidative agent. In this study, the anti-inflammatory capacity of luteolin and one of its glycosidic forms, luteolin-7-O-glucoside, were compared and their molecular mechanisms of action were analyzed. In lipopolysaccharide (LPS)-activated RAW 264.7 cells, luteolin more potently inhibited the production of nitric oxide (NO) and prostaglandin E2 as well as the expression of their corresponding enzymes (inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) than luteolin-7-O-glucoside. The molecular mechanisms underlying these effects were investigated to determine whether the inflammatory response was related to the transcription factors, nuclear factor (NF)-${\kappa}B$ and activator protein (AP)-1, or their upstream signaling molecules, mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K). Luteolin attenuated the activation of both transcription factors, NF-${\kappa}B$ and AP-1, while luteolin-7-O-glucoside only impeded NF-${\kappa}B$ activation. However, both flavonoids inhibited Akt phosphorylation in a dose-dependent manner. Consequently, luteolin more potently ameliorated LPS-induced inflammation than luteolin-7-O-glucoside, which might be attributed to the differentially activated NF-${\kappa}B$/AP-1/PI3K-Akt pathway in RAW 264.7 cells.

양자역학으로 π-π interaction 에너지 계산을 통한 ligand binding energy 분석

  • Lee, Seung-Jin;Yun, Ji-Hui;Jang, Seong-Min;Cho, Art E.
    • Proceeding of EDISON Challenge
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    • 2013.04a
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    • pp.89-100
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    • 2013
  • 생물정보학의 다양한 이론적 내용과 계산적 방법들이 갈수록 전문화 되어짐에 따라 신약 개발, 신 물질 합성, 단백질의 구조 예측 등 다양한 분야에서 필요성이 커져가고 있다. 이 중 molecular docking 기술은 단백질과 특정 분자간의 결합 형태를 분자 모델링 기법을 통해 알아내는 방법이며 신약개발 연구에 큰 영향을 미치고 있다. Molecular docking을 통하여 분자간의 결합 형태를 예측하는 과정에서 Protein-ligand complex의 정확한 에너지 측정을 가능하게 하는 scoring function이 필요하다. 그런데 본 연구에서 사용한 B-Raf kinase protein 은 active site 부분에서 ligand와 receptor 간에 aromatic ring로 인한 ${\pi}-{\pi}$ interaction이 정확한 에너지 계산을 어렵게 한다. 이러한 ${\pi}-{\pi}$ interaction 부분의 에너지를 정확하게 계산하기 위해 양자역학 계산을 실시하였다. Active site 부분에서 ligand와 receptor에서 발생하는 각각 다른 5개의 ${\pi}-{\pi}$ interaction 구조를 준비하여 Gaussian을 통해 양자역학 에너지를 계산하였다. 그리고 이러한 결과 값들이 ligand의 활성 값과 어떤 상관관계를 갖는지 살펴보았다. 그 결과 ${\pi}-{\pi}$ interaction을 양자역학으로 계산한 값이 그렇지 않은 것보다 더 좋은 상관관계를 보여주었다. 이는 특별한 구조의 영향으로 ligand와 receptor 간의 결합에너지를 정확하게 계산하기 어려운 문제에서 양자역학을 적용할 경우 더욱 좋은 결과값을 얻을 수 있었다. 또한 이러한 데이터가 신 물질 개발이나 신약 개발 등의 다양한 분야에서 계산화학 방법이 신뢰성을 얻는데 도움 될 수 있다고 생각된다.

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Transparent Polyimide Nanocomposite Films with Various Equi-biaxial Stretching Ratios (다양한 이축연신 비율에 따른 투명 폴리이미드 나노복합체 필름)

  • Kim, Young-Min;Chang, Jin-Hae
    • Polymer(Korea)
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    • v.36 no.4
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    • pp.478-485
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    • 2012
  • A series of transparent polyimide (PI) nanocomposite films was synthesized from bicyclo(2,2,2)oct-7-ene-2,3,5,6-tetracarboxylic dianhydride (BTDA) and 1,3-bis(3-aminophenoxy)benzene (BAPB) with various organoclay contents via solution intercalation polymerization to poly(amic acid)s, followed by thermal imidization. Varying organoclay loading in a range of 0 to 1.5 wt% produced variations in the optical transparency, morphology, and oxygen barrier property of the hybrids. An optimum oxygen barrier property was observed for the hybrids containing 1.0 wt% Cloisite 30B; these properties were degraded gradually by further increases in the clay content. The PI hybrid films were found to exhibit excellent optical transparency and almost no color. However, the transparency of the hybrid films decreased slightly with increasing organoclay content. Transparent PI hybrid films containing 1.0 wt% Cloisite 30B were stretched equi-biaxially with various stretching ratios in a range of 100-140% to investigate their optical transparency and oxygen permeability in detail; the variations of clay dispersion and morphology were also determined as a function of equi-biaxial stretching ratio. PI hybrid films with ${\geq}120%$ stretching were found to contain homogeneously dispersed clay in the polymer matrix and exfoliated nanocomposites. The highest barrier to oxygen permeation was found at an equi-biaxial stretching ratio of 130%.

Different Immunology Mechanisms of Phellinus igniarius in Inhibiting Growth of Liver Cancer and Melanoma Cells

  • Zhou, Cui;Jiang, Song-Song;Wang, Cui-Yan;Li, Rong;Che, Hui-Lian
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3659-3665
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    • 2014
  • To assess inhibition mechanisms of a Phellinus igniarius (PI) extract on cancer, C57BL/6 mice were orally treated with PI extractive after or before implanting H22 (hepatocellular carcinoma ) or B16 (melanoma) cells. Mice were orally gavaged with different doses of PI for 36 days 24h after introduction of H22 or B16 cells. Mice in another group were orally treated as above daily for 42 days and implanted with H22 cells on day 7. Then the T lymphocyte, antibody, cytokine, LAK, NK cell activity in spleen, tumor cell apoptosis status and tumor inhibition in related organs, as well as the expression of iNOS and PCNA in tumor tissue were examined. The PI extract could improve animal immunity as well as inhibit cancer cell growth and metastasis with a dose-response relationship. Notably, PI's regulation with the two kinds of tumor appeared to occur in different ways, since the antibody profile and tumor metastasis demonstrated variation between animals implanted with hepatocellular carcinoma and melanoma cells.

HearCAM Embedded Platform Design (히어 캠 임베디드 플랫폼 설계)

  • Hong, Seon Hack;Cho, Kyung Soon
    • Journal of Korea Society of Digital Industry and Information Management
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    • v.10 no.4
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    • pp.79-87
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    • 2014
  • In this paper, we implemented the HearCAM platform with Raspberry PI B+ model which is an open source platform. Raspberry PI B+ model consists of dual step-down (buck) power supply with polarity protection circuit and hot-swap protection, Broadcom SoC BCM2835 running at 700MHz, 512MB RAM solered on top of the Broadcom chip, and PI camera serial connector. In this paper, we used the Google speech recognition engine for recognizing the voice characteristics, and implemented the pattern matching with OpenCV software, and extended the functionality of speech ability with SVOX TTS(Text-to-speech) as the matching result talking to the microphone of users. And therefore we implemented the functions of the HearCAM for identifying the voice and pattern characteristics of target image scanning with PI camera with gathering the temperature sensor data under IoT environment. we implemented the speech recognition, pattern matching, and temperature sensor data logging with Wi-Fi wireless communication. And then we directly designed and made the shape of HearCAM with 3D printing technology.

Public key broadcast encryption scheme using new converting method

  • Jho, Nam-Su;Yoo, Eun-Sun;Rhee, Man-Young
    • Journal of the Korea Institute of Information Security & Cryptology
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    • v.18 no.6B
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    • pp.199-206
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    • 2008
  • Broadcast encryption is a cryptographical primitive which is designed for a content provider to distribute contents to only privileged qualifying users through an insecure channel. Anyone who knows public keys can distribute contents by means of public key broadcast encryption whose technique can also be applicable to many other applications. In order to design public key broadcast encryption scheme, it should devise some methods that convert a broadcast encryption scheme based on symmetric key cryptosystem to a public key broadcast encryption. Up to this point, broadcast encryption scheme on trial for converting from symmetric key setting to asymmetric public key setting has been attempted by employing the Hierarchical Identity Based Encryption (HIBE) technique. However, this converting method is not optimal because some of the properties of HIBE are not quite fitting for public key broadcast schemes. In this paper, we proposed new converting method and an efficient public key broadcast encryption scheme Pub-PI which is obtained by adapting the new converting method to the PI scheme [10]. The transmission overhead of the Pub-PI is approximately 3r, where r is the number of revoked users. The storage size of Pub-PI is O($c^2$), where c is a system parameter of PI and the computation cost is 2 pairing computations.