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DA-9601, a standardized extract of Artemisia asiatica, blocks TNF-α-induced IL-8 and CCL20 production by inhibiting p38 kinase and NF-κ-B pathways in human gastric epithelial cells

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World Journal of Gastroenterology 2006年第30期12卷 4850-4858页

作者： Suck-Chei Choi Eun-Ju Choi hyun-mee oh SungGa Lee Jeong-Kun Lee Meung-Su Lee Yong-Il Shin Suck-Jun Choi Jeong-Ryong Chae Kang-Min Lee Won-Jung Lee Jae-Sik Park Chang-Yell Shin Tae-Young oh Chang-Duk Jun Digestive Disease Research Institute Wonkwang University School of Medicine Iksan Chonbuk 570-749 Korea Department Physical Education Kunsan National University Chonbuk 573-701 Korea Department of Life Science Gwangju Institute of Science and Technology Gwangju 500-712 Korea Department of Leisure Sports Wonkwang Health Science College Iksan Chonbuk 570-749 Korea Division of Biological Sciences College of Natural Science Chonbuk National University Jeonju Chonbuk 561-756 Korea Department of Physiology Kyungpook National University School of Medicine Taegu 700-422 Korea Research Institute Dong-A Pharmaceutical Co. Ltd. Yongin 449-905 Korea

AIM: To investigate whether, or how, DA-9601, which is a new gastroprotective agent, inhibits TNF-α-induced inflammatory signals in gastric epithelial AGS cells. METHODS: Cell viability was determined by MTT assay. IL-8 and CCL20 promoter activities were determined by a luciferease reporter gene assay. NF-κB-dependent transcriptional activity was determined by I-κBαdegradation, NF-κB p65 nuclear translocation and a luciferase activity assay. IL-8 and CCL20 gene expression and protein secretion were determined by RT-PCR and an enzymelinked immunosorbent assay (ELISA). Total and phos-phorylated forms of mitogen-activated protein kinases (MAPKs) were determined by Western blot. RESULTS: Treatment of AGS cells with DA-9601 reduced TNF-α-induced IL-8 and CCL20 promoter activities, as well as their gene expression and protein release. TNF-αalso induced NF-κB-dependent transcriptional activity in AGS cells. In contrast, in cells treated with DA-9601, TNF-α-induced NF-κB activity was significantly blocked. Although all three MAP kinase family members were phosphorylated in response to TNF-α, a selective inhibitor of p38 kinase SB203580 only could inhibit both NF-κB-dependent transcriptional activity and IL-8 and CCL20 production, suggesting a potential link between p38 kinase and NF-κB-dependent pathways in AGS cells. Interestingly, DA-9601 also selectively inhibited p38 kinase phosphorylation induced by TNF-α. CONCLUSION: DA-9601 blocked TNF-α-mediated inflammatory signals by potentially modulating the p38 kinase pathway and/or a signal leading to NF-κBdependent pathways in gastric epithelial cells.

关键词： CCL20 IL-8 Artemisia asiatica DA-9601 TNF-α p38 kinase NF-κB

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Effect of Meteorological Data Assimilation on Regional Air Quality Forecasts over the Korean Peninsula

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Journal of Meteorological Research 2024年第2期38卷 262-284页

作者： Yunjae CHO hyun mee KIM Eun-Gyeong YANG Yonghee LEE Jae-Bum LEE Soyoung HA Department of Atmospheric Sciences Yonsei UniversitySeoul 03722Republic of Korea Air Quality Forecasting Center National Institute of Environmental ResearchIncheon 22689Republic of Korea National Center for Atmospheric Research BoulderCO 80305USA University of Maryland Baltimore County BaltimoreMD 21250USA Global Modeling and Assimilation Office NASA Goddard Space Flight CenterGreenbeltMD 20771USA

The Weather Research and Forecasting model coupled with Chemistry(WRF-Chem),a type of online coupled chemistry-meteorology model(CCMM),considers the interaction between air quality and meteorology to improve air quality *** data assimilation(DA)can be used to reduce uncertainty in meteorological field,which is one factor causing prediction uncertainty in the *** this study,WRF-Chem and three-dimensional variational DA were used to examine the impact of meteorological DA on air quality and meteorological forecasts over the Korean *** nesting model domains were configured over East Asia(outer domain)and the Korean Peninsula(inner domain).Three experiments were conducted by using different DA domains to determine the optimal model domain for the meteorological *** the meteorological DA was performed in the outer domain or both the outer and inner domains,the root-mean-square error(RMSE),bias of the predicted particulate matter(PM)concentrations,and the RMSE of predicted meteorological variables against the observations were smaller than those in the experiment where the meteorological DA was performed only in the inner *** indicates that the improvement of the synoptic meteorological fields by DA in the outer domain enhanced the meteorological initial and boundary conditions for the inner domain,subsequently improving air quality and meteorological *** to the experiment without meteorological DA,the RMSE and bias of the meteorological and PM variables were smaller in the experiments with *** effect of meteorological DA on the improvement of PM predictions lasted for approximately 58-66 h,depending on the ***,the uncertainty reduction in the meteorological initial condition by the meteorological DA contributed to a reduction of the forecast errors of both meteorology and air quality.

关键词： meteorological data assimilation regional air quality forecast particulate matter concentration optimal model domain forecast error WRF-Chem

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Effect of Doubling the Ensemble Size on the Performance of Ensemble Prediction in the Warm Season Using MOGREPS Implemented at the KMA

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Advances in Atmospheric Sciences 2013年第5期30卷 1287-1302页

作者： Jun Kyung KAY hyun mee KIM Young-Youn PARK Joohyung SON Department of Atmospheric Sciences Yonsei University Korea Meteorological Administration

Using the Met Office Global and Regional Ensemble Prediction System （MOGREPS） implemented at the Korea Meteorological Administration （KMA）, the effect of doubling the ensemble size on the performance of ensemble prediction in the warm season was evaluated. Because a finite ensemble size causes sampling error in the full forecast probability distribution function （PDF）, ensemble size is closely related to the efficiency of the ensemble prediction system. Prediction capability according to doubling the ensemble size was evaluated by increasing the number of ensembles from 24 to 48 in MOGREPS implemented at the KMA. The initial analysis perturbations generated by the Ensemble Transform Kalman Filter （ETKF） were integrated for 10 days from 22 May to 23 June 2009. Several statistical verification scores were used to measure the accuracy, reliability, and resolution of ensemble probabilistic forecasts for 24 and 48 ensemble member forecasts. Even though the results were not significant, the accuracy of ensemble prediction improved slightly as ensemble size increased, especially for longer forecast times in the Northern Hemisphere. While increasing the number of ensemble members resulted in a slight improvement in resolution as forecast time increased, inconsistent results were obtained for the scores assessing the reliability of ensemble prediction. The overall performance of ensemble prediction in terms of accuracy, resolution, and reliability increased slightly with ensemble size, especially for longer forecast times.

关键词： ensemble prediction ensemble size ensemble transform Kalman filter

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Effects of ethanol on the tonicity of corporal tissue and the intracellular Ca^2＋ concentration of human corporal smooth muscle cells

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Asian Journal of Andrology 2010年第6期12卷 890-898页

作者： Sung Chul Kam mee Ree Chae Ji Young Kim Seol Ho Choo Deok hyun Han Sung Won Lee Department of Urology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul 135-710 Korea

Heavy alcohol consumption is associated with an increased risk of erectile dysfunction （ED）; however, the acute effects of ethanol （Etoh） on penile tissue are not fully understood. We sought to investigate the effects of Etoh on corporal tissue tonicity, as well as the intracellular Ca^2＋ concentration （[Ca^2＋]i） and potassium channel activity of corporal smooth muscle. Strips of corpus cavernosum （CC） from rabbits were mounted in organ baths for isometric tension studies. Electrical field stimulation （EFS） was applied to strips precontracted with 10 μmol L^-1 phenylephrine as a control. Etoh was then added to the organ bath and incubated before EFS. The [Ca^2＋]i levels were monitored by the ratio of fura-2 fluorescence intensities using the fura-2 loading method. Single-channel and whole-cell currents were recorded by the conventional patch-clamp technique in short-term cultured smooth muscle cells from human CC tissue. The corpus cavernosal relaxant response of EFS was decreased in proportion to the concentration of Etoh. Etoh induced a sustained increase in [Ca^2＋]i in a dose-dependent manner, Extracellular application of Etoh significantly increased whole-cell K^＋ currents in a concentration-dependent manner （P 〈 0.05）. Etoh also increased the open probability in cell-attached patches; however, in inside-out patches, the application of Etoh to the intracellular aspect of the patches induced slight inhibition of Ca^2＋-activated potassium channel （KCa） activity. Etoh caused a dose-dependent increase in cavemosal tension by alterations to [Ca^2＋]i. Although Etoh did not affect KCa channels directly, it increased the channel activity by increasing [Ca^2＋]i. The increased corpus cavemosal tone caused by Etoh might be one of the mechanisms of ED after heavy drinking.

关键词： alcohol Ca^2+-activated potassium channel corporal smooth muscle penile erection

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Prognosis of hepatocellular carcinoma expressing cytokeratin 19:Comparison with other liver cancers

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World Journal of Gastroenterology 2012年第34期18卷 4751-4757页

作者： Jung Il Lee Jin-Woo Lee Joon mee Kim Ja Kyung Kim hyun Jung Chung Young Soo Kim Department of Internal Medicine School of MedicineInha UniversityIncheon 400-711South Korea Department of Pathology School of MedicineInha UniversityIncheon 400-711South Korea Department of Internal Medicine Yonsei University College of MedicineGangnam Severance HospitalSeoul 135-720South Korea

AIM:To investigate whether expressing biliary phenotype predicted poor outcome after the surgical treatment in primary liver cancers. METHODS:Out of 204 patients that underwent liver resection due to hepatocellular carcinoma (HCC), liver specimens of 70 patients with HCC were evaluated for biliary components by cytokeratin (CK) 19 immunostain (CK19 - HCC and CK19 + HCC). CK19 positivity was defined as membranous and/or cytoplasmic expression in ≥ 5% of tumor cells with moderate or strong intensity. Patients with other primary liver cancers, such as com- bined HCC and cholangiocarcinoma (cHCC-CC), intrahe- patic cholangiocarcinoma (ICC) who received curative liver resection, were also included in the study. Clinical characteristics of CK19-HCC and CK19 + HCC patients, including survival outcome after curative liver resection, were compared with that of cHCC-CC and ICC patients. RESULTS: The overall survival (OS) rate of CK19 - HCC(n = 49) after the curative surgical treatment was 90.7%, and 80.4% at 1 and 5 years after the resection. OS rate of CK19 + HCC (n = 21) was 74.3%, 28.9% and OS rate of cHCC-CC (n = 22) was 66.7%, 32.2% at 1 and 5 years after the surgery. For ICC (n = 19), 1 and 5-year-OS rate was 50.2% and 14.3% after the cura-tive resection. The OS rates of CK19 + HCC and cHCC-CC were significantly lower than that of CK19-HCC, but higher than the OS rate of ICC (P = 0.000). There was no statistically significant difference in OS rate between CK19 + HCC and cHCC-CC. The disease free survival (DFS) rate of CK19-HCC was 72.0% and 54.5% at 1 and 3 years after the surgical treatment. DFS rate of CK19 + HCC was 53.3%, 34.3% and DFS rate of cHCC- CC was 51.5%, 39.2% at 1 and 3 years after the resection. For ICC, 1 and 3-year-DFS rate was 28.0% and 14.0% after the curative resection. DFS rate of CK19-HCC was significantly higher than that of ICC (P = 0.017), but marginally higher than DFS rate of either CK19 + HCC or cHCC-CC (P = 0.097, P = 0.089, respec-tively).

关键词： Cytokeratin 19 Hepatocellular carcinoma Intrahepatic cholangiocarcinoma Liver cancers Hepa-tectomy

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Sutureless contact lens-type amniotic membrane for persistent epithelial defects after infectious keratitis

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International Journal of Ophthalmology(English edition) 2022年第8期15卷 1404-1406页

作者： Jung Hye Shin Young-Ho Jung hyun Beom Song mee Kum Kim Chang Ho Yoon Department of Ophthalmology Seoul National University Hospital101 Daehak-roJongno-guSeoul 03080Republic of Korea Department of Ophthalmology Seoul National University College of Medicine103 Daehak-roJongno-guSeoul 03080Republic of Korea Laboratory of Ocular Regenerative Medicine and Immunology Biomedical Research InstituteSeoul National University Hospital101 Daehak-roJongno-guSeoul 03080Republic of Korea Department of Medical Science Seoul National University College of Medicine103 Daehak-roJongno-guSeoul 03080Republic of Korea

Dear Editor,We are writing to present two case reports of persistent epithelial defect after infectious keratitis successfully treated with sutureless contact lens-type amniotic membrane(AM)*** keratitis is one of the leading causes of corneal *** disrupts the normal corneal healing process and induces inflammation,limbal cell dysfunction,and corneal surface irregularity,which can lead to corneal opacities or persistent epithelial defects(PEDs)[1].Untreated PED can cause corneal thinning,resulting in corneal perforation.

关键词： keratitis healing corneal

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Novel dual inhibitor for targeting PIM1 and FGFR1 kinases inhibits colorectal cancer growth in vitro and patient-derived xenografts in vivo

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Acta Pharmaceutica Sinica B 2022年第11期12卷 4122-4137页

作者： Fanxiang Yin Ran Zhao Dhilli Rao Gorja Xiaorong Fu Ning Lu Hai Huang Beibei Xu Hanyong Chen Jung-hyun Shim Kangdong Liu Zhi Li Kyle Vaughn Laster Zigang Dong mee-hyun Lee Department of Pathophysiology School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001China China-US(Henan)Hormel Cancer Institute Zhengzhou 450008China Translational Medical Center the First Affiliated Hospital of Zheng zhou UniversityZhengzhou 450052China The Hormel Institute University of MinnesotaAustinMN 55912USA Department of Biomedicine Health&Life Convergencen ScienceBK21 FourCollege of Pharmacy Mokpo National UniversityJeonnam 58554Republic of Korea The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention Zhengzhou 450001China Department of General Surgery the Affiliated Tumor Hospital of Zhengzhou UniversityZhengzhou 450008China College of Korean Medicine Dongshin UniversityNaju 58245Republic of Korea

Colorectal cancer(CRC) is the second most common cause of cancer-related death in the world. The pro-viral integration site for Moloney murine leukemia virus 1(PIM1) is a proto-oncogene and belongs to the serine/threonine kinase family, which are involved in cell proliferation, migration,and apoptosis. Fibroblast growth factor receptor 1(FGFR1) is a tyrosine kinase that has been implicated in cell proliferation, differentiation and migration. Small molecule HCI-48 is a derivative of chalcone, a class of compounds known to possess anti-tumor, anti-inflammatory and antibacterial effects. However,the underlying mechanism of chalcones against colorectal cancer remains unclear. This study reports that HCI-48 mainly targets PIM1 and FGFR1 kinases, thereby eliciting antitumor effects on colorectal cancer growth in vitro and in vivo. HCI-48 inhibited the activity of both PIM1 and FGFR1 kinases in an ATPdependent manner, as revealed by computational docking models. Cell-based assays showed that HCI-48inhibited cell proliferation in CRC cells(HCT-15, DLD1, HCT-116 and SW620), and induced cell cycle arrest in the G2/M phase through modulation of cyclin A2. HCI-48 also induced cellular apoptosis, as evidenced by an increase in the expression of apoptosis biomarkers such as cleaved PARP, cleaved caspase 3 and cleaved caspase 7. Moreover, HCI-48 attenuated the activation of downstream components of the PIM1 and FGFR1 signaling pathways. Using patient-derived xenograft(PDX) murine tumor models,we found that treatment with HCI-48 diminished the PDX tumor growth of implanted CRC tissue expressing high protein levels of PIM1 and FGFR1. This study suggests that the inhibitory effect of HCI-48 on colorectal tumor growth is mainly mediated through the dual-targeting of PIM1 and FGFR1kinases. This work provides a theoretical basis for the future application of HCI-48 in the treatment of clinical CRC.

关键词： PIM1 FGFR1 Colorectal cancer HCI-48 Targeted therapy Small moleculecompound ofchalcone Patient-derived xenograft model ATPKinase activity

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Effects of Ginkgo biloba extracts with mirodenafil on the relaxation of corpus cavernosal smooth muscle and the potassium channel activity of corporal smooth muscle cells

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Asian Journal of Andrology 2011年第5期13卷 742-746页

作者： Jung Jun Kim Deok hyun Han Soo hyun Lim Tae Hun Kim mee Ree Chae Kyung Jin Chung Sung Chul Kam Ju-Hong Jeon Jong Kwan Parks Sung Won Lee Department of Urology Samsung Medical Center Sungkyunkwan University School of Medicine Seou1135-710 Korea Department of Urology Gachon University Gil Hospital Incheon 405-760 Korea Department of Urology Gyeengsang National University College of Medicine Gyeongsangnam-do 660-702 Korea Department of Physiology and Biophysics Seeul National University College of Medicine Seeul 110-799 Korea Department of Urology Medical School Chonbuk National University and Institute for Medical Sciences Chonbuk National University and Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University Hospital Jeonju-si 561-712 Korea

In this study, we investigated the effects of a combination of Ginkgo biloba extracts （GBE） and phosphodiesterase type 5 （PDE-5） inhibitors on the muscular tone of the corpus cavernosum and potassium channel activity of corporal smooth muscle cells. Strips of corpus cavernosum from male New Zealand white rabbits were mounted in organ baths for isometric tension studies. After contraction with 1 × 10^-5 mol I^-1 norepinephrine, GBE （0.01-1 mg ml^-1） and mirodenafil （0.01-100 nmol I^-1） were added together into the organ bath. In electrophysiological studies, whole-cell currents were recorded by the conventional patch-clamp technique in cultured smooth muscle cells of the human corpus cavernosum. The corpus cavemosum was relaxed in response to GBE in a dose-dependent manner （from 0.64%±8.35% at 0.01 mg ml^-1 to 52.28%±11.42% at 1 mg ml^-1）. After pre-treatment with 0.03 mg ml^-1 of GBE, the relaxant effects of mirodenafil were increased at all concentrations, After tetraethylammonium （TEA）（1 mmol I^-1） administration, the increased effects were inhibited （P〈0.01）. Extracellular administration of GBE increased the whole-cell K^＋ outward currents in a dose-dependent fashion. The increase of the outward current was inhibited by I mmol 1-1 TEA. These results suggest that GBE could increase the relaxant potency of mirodenafil even at a minimally effective dose. The K＋ flow through potassium channels might be one of the mechanisms involved in this synergistic relaxation.

关键词： calcium-activated potassium channels erectile dysfunction Ginkgo biloba phosphodiesterase inhibitors smooth muscles

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Association of low muscle strength with metabolic dysfunctionassociated fatty liver disease:A nationwide study

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World Journal of Gastroenterology 2023年第45期29卷 5962-5973页

作者： Gyu Bae Lee Youn Huh Sang hyun Lee Byoungduck Han Yang-hyun Kim Do-Hoon Kim Seon mee Kim Youn Seon Choi Kyung Hwan Cho Ga Eun Nam Department of Family Medicine Korea University College of MedicineSeoul 02841South Korea Department of Family Medicine Uijeongbu Eulji Medical CenterEULJI UniversityDaejeon 11759South Korea School of Electrical Engineering Korea UniversitySeoul 02841South Korea

BACKGROUND There is limited evidence regarding the association between muscle strength and metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the association between muscle strength and MAFLD in the general population in *** This nationwide representative cross-sectional study included 31649 individuals aged≥19 years who participated in the Korea National Health and Nutrition Examination Survey between 2015 and *** ratios(ORs)and 95%confidence intervals(95%CIs)for MAFLD according to sex-specific quartiles of muscle strength,defined by relative handgrip strength,were calculated using multivariable logistic regression ***,multivariable logistic regression analysis was used to assess the association between muscle strength and probable liver fibrosis in patients with *** Of all the participants,29.3%had *** prevalence of MAFLD was significantly higher in the lower muscle strength quartile groups for all participants,sexes,and age groups(P<0.001).A 1.92-fold(OR=1.92,95%CI:1.70–2.16)and 3.12-fold(OR=3.12,95%CI:2.64–3.69)higher risk of MAFLD was observed in the lowest quartile(Q1)group than in the other groups(Q2–Q4)and the highest quartile(Q4)group,*** ORs of MAFLD were significantly increased in the lower muscle strength quartile groups in a dose-dependent manner(P for trend<0.001).These associations persisted in both *** inverse association between muscle strength and the risk of MAFLD was observed in all subgroups according to age,obesity,and diabetes *** patients with MAFLD,the odds of severe liver fibrosis were higher in Q1(OR=1.83,95%CI:1.25–2.69)than in other groups(Q2–Q4).CONCLUSION Among Korean adults,low muscle strength was associated with an increased risk of MAFLD and liver fibrosis in patients with MAFLD.

关键词： Muscle strength Handgrip strength Metabolic dysfunction-associated fatty liver disease Liver fibrosis Korea National Health and Nutrition Examination Survey

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SIMULA在Cu/ZnO/Al_2O_3催化剂上进行甲醇部分氧化蒸气重整制备氢气的模拟研究(英文)

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燃料化学学报 2001年第3期29卷 207-213页

作者：蒋元力黄强王福安 mee Sook Lim Dong hyun Kim 郑州工业大学化工学院 DepartmentofChemicalEngineering KyungpookNationalUniversityTaegu702701Korea

两个大气压下 ,对管状填充床反应器中在Cu ZnO Al2 O3催化剂上甲醇部分氧化蒸气重整制备氢气进行了实验研究。在Cu ZnO Al2 O3催化剂上进行该反应体系动力学研究的基础上 ,建立了该反应器内的稳态质量和热量衡算方程 ,同时考虑了颗粒内... 详细信息

两个大气压下 ,对管状填充床反应器中在Cu ZnO Al2 O3催化剂上甲醇部分氧化蒸气重整制备氢气进行了实验研究。在Cu ZnO Al2 O3催化剂上进行该反应体系动力学研究的基础上 ,建立了该反应器内的稳态质量和热量衡算方程 ,同时考虑了颗粒内的扩散限制。模型的预测结果与实验结果吻合较好。

关键词：氢气制备模拟质量衡算热量衡算部分氧化蒸气重整甲醇铜氧化锌氧化铝催化剂

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