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.

Relationship Between K_trans and K₁ with Simultaneous Versus Separate MR/PET in Rabbits with VX2 Tumors

Lee, K. H.,Kang, S. K.,Goo, J. M.,Lee, J. S.,Cheon, G. J.,Seo, S.,Hwang, E. J. INTERNATIONAL INSTITUTE OF ANTICANCER RESEARCH 2017 Anticancer research Vol.37 No.3

<P>Background/Aim: To compare the relationship between Ktrans from DCE-MRI and K1 from dynamic (NNH3)-N-13- PET, with simultaneous and separate MR/PET in the VX-2 rabbit carcinoma model. Materials and Methods: MR/PET was performed simultaneously and separately, 14 and 15 days after VX-2 tumor implantation at the paravertebral muscle. The Ktrans and K-1 values were estimated using an in-house software program. The relationships between Ktrans and K-1 were analyzed using Pearson's correlation coefficients and linear/non-linear regression function. Results: Assuming a linear relationship, Ktrans and K-1 exhibited a moderate positive correlations with both simultaneous ( r=0.54-0.57) and separate ( r=0.53-0.69) imaging. However, while the Ktrans and K-1 from separate imaging were linearly correlated, those from simultaneous imaging exhibited a non-linear relationship. The amount of change in K-1 associated with a unit increase in Ktrans varied depending on Ktrans values. Conclusion: The relationship between K-trans and K-1 may be mis-interpreted with separate MR and PET acquisition.</P>

Phase II study of S-1 combined with oxaliplatin as therapy for patients with metastatic biliary tract cancer: influence of the <i>CYP2A6</i> polymorphism on pharmacokinetics and clinical activity

Kim, K-p,Jang, G,Hong, Y S,Lim, H-S,Bae, K-s,Kim, H-S,Lee, S S,Shin, J-G,Lee, J-L,Ryu, M-H,Chang, H-M,Kang, Y-K,Kim, T W Nature Publishing Group 2011 The British journal of cancer Vol.104 No.4

<P><B>Background:</B></P><P>Advanced biliary cancer is often treated with fluoropyrimidine-based chemotherapy. In this study, we evaluated the efficacy and tolerability of a combination of S-1, an oral fluoropyrimidine prodrug, and oxaliplatin in patients with metastatic biliary cancer.</P><P><B>Methods:</B></P><P>Patients with histologically confirmed metastatic biliary cancer and no history of radiotherapy or chemotherapy were enrolled. Oxaliplatin was administered intravenously (130 mg m<SUP>−2</SUP>), followed by 14-day administration of oral S-1 (40 mg m<SUP>−2</SUP> twice daily) with a subsequent 7-day rest period every 21 days. Pharmacokinetic analysis of S-1 was performed at cycle 1. Patients were genotyped for <I>CYP2A6</I> polymorphisms (<SUP>*</SUP>1, <SUP>*</SUP>4, <SUP>*</SUP>7, <SUP>*</SUP>9 or <SUP>*</SUP>10), and pharmacokinetic and clinical parameters compared according to the <I>CYP2A6</I> genotype.</P><P><B>Results:</B></P><P>In total, 49 patients were evaluated, who received a median of four cycles. The overall response rate was 24.5%. Median progression-free and overall survival was 3.7 and 8.7 months, respectively. The most common haematological grade 3 out of 4 toxicity was neutropenia (14%), while non-hematological grade 3 out of 4 toxicities included anorexia (14%), nausea (12%), asthenia (10%), vomiting (10%), and diarrhoea (4%). Biotransformation of S-1 (AUC<SUB>0−24 h</SUB> of 5-fluorouracil/AUC<SUB>0−24 h</SUB> of tegafur) was 1.85-fold higher for the <I>*1/*1</I> group than for the other groups (90% confidence interval 1.37–2.49). Diarrhoea (<I>P</I>=0.0740), neutropenia (<I>P</I>=0.396), and clinical efficacy (response rate, <I>P</I>=0.583; PFS, <I>P</I>=0.916) were not significantly associated with <I>CYP2A6</I> genotype, despite differences in 5-FU exposure.</P><P><B>Conclusion:</B></P><P>The combination of S-1 and oxaliplatin appears to be active and well tolerated in patients with metastatic biliary cancer, and thus is feasible as a therapeutic modality. <I>CYP2A6</I> genotypes are associated with differences in the biotransformation of S-1. However, the impact of the <I>CYP2A6</I> polymorphism on variations in clinical efficacy or toxicity requires further evaluation.</P>

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>

반추위 곰팡이의 분리 · 동정과 섬유소 분해효소의 특성구명 및 이들의 산업적 이용에 관한 연구 (4) 한우 및 재래산양의 반추위에서 분리된 곰팡이의 섬유소 분해력 측정

이성실(S . S . Lee),하종규(J . K . Ha),최윤재(Y . J . Choi),한인규(In K . Han),김창현(C . H . Kim),강수현(S . H . Kang) 한국영양사료학회 1995 韓國營養飼料學會誌 Vol.19 No.5

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>

Antibiotic susceptibility and resistance of Streptococcus iniae and Streptococcus parauberis isolated from olive flounder (Paralichthys olivaceus)

Park, Y.K.,Nho, S.W.,Shin, G.W.,Park, S.B.,Jang, H.B.,Cha, I.S.,Ha, M.A.,Kim, Y.R.,Dalvi, R.S.,Kang, B.J.,Jung, T.S. Elsevier Scientific Pub. Co 2009 Veterinary microbiology Vol.136 No.1

The rates of antibiotic susceptibility and resistance were investigated in Streptococcus iniae and Streptococcus parauberis isolates obtained from diseased olive flounders (Paralichthys olivaceus) collected from fish farms in Jeju Island, Korea. Isolates of S. iniae (n=65) were susceptible to cefotaxime, erythromycin, ofloxacin, penicillin, tetracycline and vancomycin, as demonstrated by the minimum inhibitory concentration (MIC) test. Isolates of S. parauberis (n=86) were highly resistant to erythromycin (58% of the 86 isolates tested) and tetracycline (63% of the 86 isolates tested). Fifty-four isolates of tetracycline-resistant S. parauberis contained the tet(M/O/S) genes, of which 39 and 12 isolates contained the tet(M) and tet(S) genes, respectively, whereas 3 isolates contained both the tet(M) and tet(S) genes. Among the erythromycin-resistant isolates of S. parauberis (n=50) only 14 contained the erm(B) gene. These results suggest that the tet(S) and erm(B) genes of S. parauberis are involved in the acquisition of high-level resistance to erythromycin and tetracycline. Our findings reveal a high rate of antibiotic resistance among strains of S. parauberis and emphasize the need to develop an appropriate vaccine to reduce the use of antibiotics.

The prolyl isomerase Pin1 interacts with a ribosomal protein S6 kinase to enhance insulin-induced AP-1 activity and cellular transformation

Lee, N. Y.,Choi, H.-K.,Shim, J.-H.,Kang, K.-W.,Dong, Z.,Choi, H. S. Oxford University Press 2009 Carcinogenesis Vol.30 No.4

<P>Phosphorylation of proteins on serine or threonine residues that immediately precede proline (pSer/Thr-Pro) is specifically catalyzed by the peptidyl-prolyl cis-trans isomerase Pin1 and is a central signaling mechanism in cell proliferation and transformation. Although Pin1 is frequently overexpressed in hepatocellular carcinoma (HCC), the molecular mechanism of Pin1 in HCC has not been completely elucidated. Here, we show that Pin1 interacts with p70S6K in vitro and ex vivo. Overexpression of Pin1 resulted in enhanced p70S6K phosphorylation induced by insulin in SK-HEP-1 cells. In contrast, Pin1(-/-) mouse embryonic fibroblasts (MEFs) exhibited significantly decreased insulin-induced p70S6K phosphorylation compared with Pin1(+/+) MEFs. Furthermore, Pin1 enhanced the insulin-induced extracellular signal-regulated protein kinase (ERK)1/2 phosphorylation through its interaction with p70S6K, whereas the inhibition of p70S6K activity by rapamycin suppressed insulin-induced ERK1/2 phosphorylation in SK-HEP-1 cells. Hence, Pin1 affected activator protein-1 activity through p70S6K-ERK1/2 signaling in SK-HEP-1 cells. Most importantly, Pin1-overexpressing JB6 Cl41 cells enhanced neoplastic cell transformation promoted by insulin much more than green fluorescent protein-overexpressing JB6 Cl41 control cells. These results imply that Pin1 amplifies insulin signaling in hepatocarcinoma cells through its interaction with p70S6K, suggesting that Pin1 plays an important role in insulin-induced tumorigenesis and is a potential therapeutic target in hepatocarcinoma.</P>

Development of a systematic, self-consistent algorithm for the K-DEMO steady-state operation scenario

Kang, J.S.,Park, J.M.,Jung, L.,Kim, S.K.,Wang, J.,Lee, C.Y.,Na, D. H.,Im, K.,Na, Y.-S.,Hwang, Y.S. IOP 2017 Nuclear fusion. Fusion nucléaire. &n.Illiga Vol.57 No.12

<P>An optimum plasma pressure/current density profile and corresponding heating/current drive (H/CD) determination scheme is newly developed by integrating equilibrium, stability, confinement, and H/CD, self-consistently subject to maximize the fusion gain for Korean fusion demonstration reactor (K-DEMO) steady-state operation scenarios. The integrated plasma modeling package, FASTRAN/IPS, is adopted for the integrated numerical apparatus. The target pressure profile with a pedestal structure is investigated by varying its peaking, pedestal height and width as a first step. Formation of stable equilibria is evaluated by solving the Grad–Shafranov equation and checking linear MHD stability. For the case of potentially stable equilibrium, required external heating distribution is calculated by considering both power balance and external current drive alignment to reproduce the pressure profile of the stable equilibrium. Electron/ion temperature and poloidal flux evolutions are solved with the derived heating configuration to find a steady-state scenario and achieve self-consistent plasma profiles. A self-consistent target steady-state pressure and current profile parameters are proposed through designed systematic algorithm with fusion power <I>P</I> <SUB>F</SUB>  =  2070 MW, fusion gain <I>Q</I>  =  19.7, and normalized beta <I>β</I> <SUB>N</SUB>  =  2.8 at toroidal field <I>B</I> <SUB>T</SUB>  =  7.4 T and plasma current <I>I</I> <SUB>P</SUB>  =  15.5 MA. Feasibility of fusion power <I>P</I> <SUB>F</SUB>  =  3000 MW operation is also explored with enhanced density and temperature limit assumption.</P>

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.