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      • Anti-inflammatory effects of Stephania tetrandra S. Moore on interleukin-6 production and experimental inflammatory disease models

        Kang, H-S,Kim, Y-H,Lee, C-S,Lee, J-J,Choi, I.,Pyun, K-H 충남대학교 약학대학 의약품개발연구소 1997 藥學論文集 Vol.13 No.-

        DEREGULATION of interleukin-6 (IL-6) expression caused the synthesis and release of many inflammatory mediators. It is involved in chronic inflammation, autoimmune diseases, and malignancy. Stephania tetrandra S. Moore is a Chinese medicinal herb which has been used traditionally as a remedy for neuralgia and arthritis in China. To investigate the anti-inflammatory effects of S. tetrandra S. Moore in vitro and in vivo, its effects on the production of Il-6 and inflammatory mediators were analysed. When human monocytes/macrophages stimulated with silica were treated with 0.1-10 ㎍/㎖ S. tetranda S. Moore, the production of IL-6 was inhibited up to 50%. At these concentrations, it had no cytotoxicity effect on these cells. It also suppressed the production of Il-6 by alveolar macrophages stimulated with silica. In addition, it inhibited the release of superoxide anion and hydrogen peroxide from human monocytes/macrophages. To assess the anti-fibrosis efects of S. tetrandra S. Moore, its effects on in vivo experimental inflammatory models were evaluated. In the experimental silicosis model, IL-6 activities in the sera and in the culture supernatants of pulmonary fibroblasts were also inhibited by it. In vitro and in vivo treatment of S. tetrandra S. Moore reduced collagen production by rat lung fibroblasts and lung tissue. Also, S. tetrandra S. Moore reduced the levels of serum GOT and GPT in the rat cirrhosis model induced by CCl_4, and it was effective in reducing hepatic fibrosis and nodular formation. Taken together, these data indicate that it has a potent antiinflammatory and anti-fibrosis effect by reducing IL-6 production.

      • Strategy for enhancing the solar-driven water splitting performance of TiO<sub>2</sub> nanorod arrays with thin Zn(O,S) passivated layer by atomic layer deposition

        Shin, S.W.,Suryawanshi, M.P.,Hong, H.K.,Yun, G.,Lim, D.,Heo, J.,Kang, S.H.,Kim, J.H. Pergamon Press 2016 ELECTROCHIMICA ACTA Vol.219 No.-

        An array of one dimensional (1D) TiO<SUB>2</SUB> nanorods (TONRs) has been regarded as an attractive candidate for electrochemical energy conversion and as storage device due to its large surface area, effiective light scattering, and undisturbed charge transport pathway. However, the high defect/trap densities on surface of the nanostructured morphology and architecture may generally hinder the performance enhancement by providing electron-hole recombination sites. Hence, the surface passivation of nanoarchitectures based photoelectrodes has recently received much attention as an effective strategy to enhance the charge-separation and charge-transfer processes in photoelectrochemical (PEC) water splitting devices. In particular, a coating layer with narrowing band gap materials can promote enhanced light harvesting in the UV-vis region as well as surface passivation, directly supplying a driving force for charge separation and charge transfer due to band alignment. In this paper, the surface of TONRs were passivated by 10 and 30nm thick Zn(O,S) layers with a relatively narrow band gap using an atomic layer deposition technique to modulate the thickness exactly. The 10nm Zn(O,S)/TONR array exhibits a significantly enhanced photocurrent density (J<SUB>sc</SUB>) of 5.94mA/cm<SUP>2</SUP> at 1.23eV vs NHE and an incident photon-to-electron conversion efficiency (IPCE) of 49% at 374nm compared with that of TONR arrays (J<SUB>sc</SUB> of 1.99mA/cm<SUP>2</SUP> at 1.23eV vs NHE and an IPCE of 20% at 380nm). However, the PEC performance is worse in the 30nm Zn(O,S)/TONR arrays, showing a J<SUB>sc</SUB> of 3.09mA/cm<SUP>2</SUP> at 1.23eV vs NHE and an IPCE of 29% at 374nm. To clearly demonstrate these PEC behaviors, the TONR and Zn(O,S)/TONR arrays were characterized by electrochemical impedance spectroscopy (EIS), open circuit voltage decay (OCV) measurement, and X-ray photoelectron spectroscopy (XPS). The above mentioned characterizations indicate that the enhanced PEC performance of the 10nm Zn(O,S)/TONR array resulted from the (i) increased light harvesting in the UV-vis region, (ii) lower charge transfer resistance and (iii) high value of valence band offset (VBO, -1.44eV) and conduction band offset (CBO, -1.2eV) than those of the TONR. However, the deterioration of J<SUB>sc</SUB> in the 30nm Zn(O,S)/TONR array is attributed to the negative value of VBO (-0.13eV) and positive value of CBO (+0.27eV), as well as the higher charge transfer resistance to the electrolyte than that of the TONR arrays, despite of the improved light absorption in the visible region. The photocurrent densities of 10nm Zn(O,S)/TONR and 30nm Zn(O,S)/TONR photocathodes decay to 4.718mA/cm<SUP>2</SUP> (5.90mA/cm<SUP>2</SUP> at 0min) and 2.212mA/cm<SUP>2</SUP> (3.03mA/cm<SUP>2</SUP> at 0min) after 90min, respectively, they retain of about~80% and 70% of its original values. These experimental results and discussions not only provide the physical insights into the surface passivation effect and band alignment but also can open a promising route to design the thin passivation layer having the narrowing band gap energy (1.0eV~2.5eV) on the 1D TiO<SUB>2</SUB> nanostructure for further enhanced performance and realization of a TiO<SUB>2</SUB> based PEC system.

      • Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis

        Yu, K‐,H.,Hong, K‐,S.,Lee, B‐,C.,Oh, M‐,S.,Cho, Y‐,J.,Koo, J,S.,Park, J,M.,Bae, H‐,J.,Han, M‐,K.,Ju, Y‐,S.,Kang, D‐,W.,Appelros, P. Blackwell Publishing Ltd 2011 Acta neurologica Scandinavica Vol.123 No.5

        <P>Yu K‐H, Hong K‐S, Lee B‐C, Oh M‐S, Cho Y‐J, Koo J‐S, Park J‐M, Bae H‐J, Han M‐K, Ju Y‐S, Kang D‐W, Appelros P, Norrving B, Terent A. Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis. 
Acta Neurol Scand: 2011: 123: 325–331. 
© 2010 John Wiley & Sons A/S.</P><P><B>Background – </B> It has not been clarified whether the disparity in ischemic stroke outcome between populations is caused by ethnic and geographic differences or by variations in case mix. Propensity score matching (PSM) analysis can overcome some analytical problems but is rarely used in stroke outcome research. This study was to compare the ischemic stroke case‐fatality between two PSM cohorts of Sweden and Korea.</P><P><B>Methods – </B> Prognostic variables related to baseline characteristics and stroke care were included in our PSM model. Then, we selected 7675 Swedish and 1220 Korean patients with ischemic stroke from each stroke registers and performed one‐to‐one matching based on propensity scores of each patient.</P><P><B>Results – </B> After PSM, all measured variables were well balanced in 1163 matched subjects, and the 90‐day case‐fatality was identical 6.2% (HR 0.997, 95%CI 0.905–1.099) in Sweden and Korea.</P><P><B>Conclusions – </B> No difference is found in the 90‐day case‐fatality in propensity score‐matched Swedish and Korean patients with ischemic stroke.</P>

      • Production of soluble truncated spike protein of porcine epidemic diarrhea virus from inclusion bodies of Escherichia coli through refolding

        Piao, D.C.,Lee, Y.S.,Bok, J.D.,Cho, C.S.,Hong, Z.S.,Kang, S.K.,Choi, Y.J. Academic Press 2016 Protein expression and purification Vol.126 No.-

        The emergence of highly pathogenic variant porcine epidemic diarrhea virus (PEDV) strains, from 2013 to 2014, in North American and Asian countries have greatly threatened global swine industry. Therefore, development of effective vaccines against PEDV variant strains is urgently needed. Recently, it has been reported that the N-terminal domain (NTD) of S1 domain of PEDV spike protein is responsible for binding to the 5-N-acetylneuraminic acid (Neu5Ac), a possible sugar co-receptor. Therefore, the NTD of S1 domain could be an attractive target for the development of subunit vaccines. In this study, the NTD spanning amino acid residues 25-229 (S25-229) of S1 domain of PEDV variant strain was expressed in Escherichia coli BL21 (DE3) in the form of inclusion bodies (IBs). S25-229 IBs were solubilized in 20 mM sodium acetate (pH 4.5) buffer containing 8 M urea and 1 mM dithiothreitol with 95% yield. Solubilized S25-229 IBs were refolded by 10-fold flash dilution and purified by one-step cation exchange chromatography with >95% purity and 20% yield. The CD spectrum of S25-229 showed the characteristic pattern of alpha helical structure. In an indirect ELISA, purified S25-229 showed strong reactivity with mouse anti-PEDV sera. In addition, immunization of mice with 20 μg of purified S25-229 elicited highly potent serum IgG titers. Finally, mouse antisera against S25-229 showed immune reactivity with native PEDV S protein in an immunofluorescence assay. These results suggest that purified S25-229 may have potential to be used as a subunit vaccine against PEDV variant strains.

      • SCISCIESCOPUS
      • Glutathione S-transferase M1 and T1 polymorphisms: Susceptibility and outcomes in muscle invasive bladder cancer patients

        Kang, H.w.,Song, P.H.,Ha, Y.S.,Kim, W.T.,Kim, Y.J.,Yun, S.J.,Lee, S.C.,Choi, Y.H.,Moon, S.K.,Kim, W.J. Pergamon Press 2013 European journal of cancer Vol.49 No.14

        Background: We investigated whether genetic polymorphisms in the glutathione S transferase mu (GSTM1) and theta (GSTT1) genes modulated risk, disease progression and survival in primary muscle invasive bladder cancer (MIBC). Methods: GSTM1 and GSTT1 polymorphisms were analysed by multiplex polymerase chain reaction (PCR) using blood genomic DNA in 110 MIBC patients and 220 gender- and age-matched healthy controls. The influence of the genetic polymorphisms on patient survival was evaluated by Kaplan-Meier survival curves and Cox Proportional Hazard models. We also evaluated whether cigarette smoking and treatment modality modified the association between genotype and prognosis. Results: GSTM1-null individuals exhibited increased risk for MIBC and an association with cigarette smoking. GSTT1-null subjects showed significant disease progression and cancer-specific death. In the combined analysis, GSTT1-null genotype was an independent risk factor for disease progression and cancer specific death regardless of GSTM1 genotype. Significant differences in progression-free survival (PFS) and cancer-specific survival (CSS) were seen based on GSTT1 genotype. The survival impact of the GSTT1 genotype was only valid for smokers. The GSTT1-null genotype was an independent prognostic factor for shorter PFS in patients who received chemotherapy and those who did not undergo radical cystectomy. By multivariate Cox regression analysis, GSTT1-null genotype was a predictive factor for disease progression and cancer specific survival regardless of treatment modality. Conclusions: The GSTM1-null genotype plays an important role in genetic susceptibility to MIBC and the GSTT1-null genotype is associated with disease progression and shorter survival in MIBC.

      • Identification and mechanism of action of renoprotective constituents from peat moss Sphagnum palustre in cisplatin-induced nephrotoxicity

        Kang, H.R.,Lee, D.,Eom, H.J.,Lee, S.R.,Lee, K.R.,Kang, K.S.,Kim, K.H. Elsevier 2016 Journal of Functional Foods Vol.20 No.-

        In search for bioactive constituents from natural resources, the ethanol (EtOH) extract of Sphagnum palustre showed significant renoprotective effects against cisplatin-induced damage in kidney cells. Phytochemical investigation of the EtOH extract led to the identification of a new flavonoid, 6-methyl-(2R,3S)-alpinone, along with six known flavonoids, four steroids, six triperpenoids, and three fatty acids. Among them, ergosterol peroxide, (3β,22E,24S)-3-hydroxy-ergosta-5,22-dien-7-one, and betulinic acid ameliorated cisplatin-induced nephrotoxicity to 80% of the control value at 125, 125 and 50@?@?M, respectively. Moreover, the elevated percentage of apoptotic cells by cisplatin was significantly reduced after co-treatment with the EtOH extract of S.palustre and ergosterol peroxide, (3β,22E,24S)-3-hydroxy-ergosta-5,22-dien-7-one, and betulinic acid. Upregulated phosphorylation of JNK and p38 by cisplatin treatment was markedly decreased after co-treatment with ergosterol peroxide, (3β,22E,24S)-3-hydroxy-ergosta-5,22-dien-7-one, and betulinic acid. These results show that blocking the MAPKs signalling cascade plays a critical role in mediating the renoprotective effect of S.palustre.

      • Inhibition of acetylcholinesterase and glutathione S-transferase of the pinewood nematode (Bursaphelenchus xylophilus) by aliphatic compounds

        Kang, J.S.,Moon, Y.S.,Lee, S.H.,Park, I.K. Academic Press 2013 Pesticide biochemistry and physiology Vol.105 No.3

        To determine the nematicidal mode of action of aliphatic compounds against the pinewood nematode (Bursaphelenchus xylophilus), we evaluated the inhibition activity of 63 aliphatic compounds on B. xylophilus acetylcholinesterases (BxACEs) and glutathione S-transferase. In the primary inhibition assay using B. xylophilus crude proteins, more than 65% of BxACE inhibition activity was observed for C<SUB>6</SUB>, C<SUB>9</SUB>, C<SUB>10</SUB>, and C<SUB>12</SUB> 2E-alkenals. Other compounds showed moderate or weak inhibition activity. The inhibition activity against 3 recombinant BxACEs was subsequently evaluated using active compounds in a primary inhibition assay. C<SUB>12</SUB> 2E-alkenal showed the strongest inhibition activity against BxACE-1, followed by C<SUB>9</SUB>, C<SUB>6</SUB>, and C<SUB>10</SUB> 2E-alkenals. The IC<SUB>50</SUB> values of C<SUB>12</SUB>, C<SUB>6</SUB>, C<SUB>10</SUB>, and C<SUB>9</SUB> 2E-alkenal against BxACE-2 were 0.0059, 0.57, 0.86, and 0.99mg/ml, respectively. C<SUB>12</SUB> 2E-alkenal showed the strongest inhibition activity against BxACE-3 followed by C<SUB>6</SUB> 2E-alkenal. In an inhibition activity test using glutathione S-transferase from the pinewood nematode, C<SUB>10</SUB>, C<SUB>9</SUB>, and C<SUB>6</SUB> 2E-alkenals and C<SUB>12</SUB> alkanoic acid showed >45% inhibition activity.

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        Role of Human Aquaporin 5 In Colorectal Carcinogenesis

        Kang, S.K.,Chae, Y.K.,Woo, J.,Kim, M.S.,Park, J.C.,Lee, J.,Soria, J.C.,Jang, S.J.,Sidransky, D.,Moon, C. American Association of Pathologists and Bacteriol 2008 The American journal of pathology Vol.173 No.2

        While overexpression of several aquaporins (AQPs) has been reported in different types of human cancer, the role of AQPs in carcinogenesis has not been clearly defined. Here, by immunochemistry, we have found expression of AQP5 protein in 62.8% (59/94) of resected colon cancer tissue samples as well as association of AQP5 with liver metastasis. We then demonstrated that overexpression of human AQP5 (hAQP5) induces cell proliferation in colon cancer cells. Overexpression of wild-type hAQP5 increased proliferation and phosphorylation of extracellular signal-regulated kinase-½ in HCT116 colon cancer cells whereas these phenomena in hAQP5 mutants (N185D and S156A) were diminished, indicating that both membrane association and serine/threonine phosphorylation of AQP5 are required for proper function. Interestingly, overexpression of AQP1 and AQP3 showed no differences in extracellular signal-regulated kinase-½ phosphorylation, suggesting that AQP5, unlike AQP1, may be involved in signal transduction. Moreover, hAQP5-overexpressing cells showed an increase in retinoblastoma protein phosphorylation through the formation of a nuclear complex with cyclin D1 and CDK4. Small interfering RNA analysis confirmed that hAQP5 activates the Ras signaling pathway. These data not only describe the induction of hAQP5 expression during colorectal carcinogenesis but also provide a molecular mechanism for colon cancer development through the interaction of hAQP5 with the Ras/extracellular signal-regulated kinase/retinoblastoma protein signaling pathway, identifying hAQP5 as a novel therapeutic target.

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