The Korean Society of Gastroenterology & SIDDS 2040 : Slide Session ;K-LG-11 : Lower GI Tract ; Guggulsterone Ameliorates Colitis by Blocking Crosstalk Between Nf-κb and Trem-1

( Soo Jung Park ),( Ki Cheong Park ),( You Hyun Kang ),( Hyun A Jin ),( Xiu Mei Che ),( Seung Won Kim ),( Sung Pil Hong ),( Tae Il Kim ),( Won Ho Kim ),( Jae Hee Cheon ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Triggering receptor expressed on myeloid cells (TREM)-1 constitutively expressed in macrophage, and upregulated by bacterial components, such as lipopolysaccharide (LPS), and functions as an amplifying molecule in infi ammatory responses. Recent studies have reported that TREM-1 expression is up-regulated in patients with infi ammatory bowel disease (IBD). In this study, we expected that guggulsterone (GGS) functions as reducer of TREM-1 in macrophage and investigated the anti-infi ammatory effects of GGS via the inhibition of NF-κB/TREM-1 in mononuclear cells using RAW264.7 activated by LPS and TNBS-induced colitis model of knockout mice. Methods: We are checked the mRNA level of TREM-1 and toll like receptor 4 (TLR4) using real time RT-PCR and the protein level of IκBa and phospho-IκBa using western blotting and ELISA, and nuclear translocation of NF-κB using immunofi uorescence. MG132 and TREM-1 antibody were used to determine the interaction of NF-κ B and TREM-1 signaling. Mouse colitis is induced by the administration of TNBS into the colon. Results: GGS treatment decreased the mRNA and protein levels of TREM-1, TLR4, TNF-a, IL-6, IL17, COX-2, and MMP-9 by blocking the phosphorylation and degradation of IκBa as well as nuclear translocation of NF-κB in RAW264.7 macrophage activated by LPS. In the TNBS-induced colitis model, GGS reduced disease activity index (DAI), and infi ammation related protein expressions by suppressing NF-κB and TREM- 1 activation in colon mucosa. Conclusions: GGS blocks the NF-κB signaling pathway by targeting the TREM-1 in RAW264.7 macrophage activated by LPS and TNBS-induced mouse colitis model. Ourresults provide an insight into the mutual relationship NF-κB and TREM-1 signaling pathway. Eventually, these fi ndings shows that GGS has a anti-infi ammatory effects in macrophage cells through the regulation of the TREM-1 and NF-κB signaling, which suggests that GGS is a potential therapeutic agent for the treatment of IBD.

노인 인구에서 신경인지기능저하와 혈청 지질농도와의 상관성

유영선,최석주,정성수,김지은,윤성욱,전동욱,백준형,박성우,이정구,추일한,김영훈 大韓神經精神醫學會 2008 신경정신의학 Vol.47 No.6

Objectives : In this study, the authors evaluated the correlation between eurocognitive impairments and serum lipids levels among Korean elderly over the age of 65. Methods : A total of 609 elderly individuals participated in this study. Screening for cognitive impairments were carried out using the Mini-Mental Status Examination-Korean version (MMSE-KC). There were 197 subjects above 1.5SD Of MMSE- KC and they were evaluated using the Korean versions of the Consortium to Establish a Registry for Alzheimer's Disease (AD) (CERAD-KC) and Geriatric Depression Scale (GDS-K). Results : There was a correlation between old age/low levels of education and AD (p<0.05, P<0.01). There was an inverse correlation between the serum level of total cholesterol and the word list recognition test scores. The serum levels of LDL cholesterol were inversely correlated with the scores on the constructional praxis test, word list recall test and word list recognition test. Inverse correlations between the serum level of triglyceride and scores on the word list recall test and word list recognition test were also observed. Conclusion : There were inverse correlations between the serum levels of lipids and language/memory function in subjects with AD.

난소암에서 CA125의 임상적 의의

윤병일,김수녕,손인숙,유연웅,최원석 건국대학교 의과학연구소 2000 건국의과학학술지 Vol.10 No.-

The concentration of the tumor marker CA125 in serum from patients with ovarian tumor was measured to define the usefulness of them in differentiating malignant ovarian tumor from benign ovarian mass. In the study of 105 patients with gynecologic neoplasm, of whom 38 were myoma uteri, 42 benign ovarian tumor, and 25 ovarian cancer, the level of serum CA125 were measured. CA125 was greater than 35 U/ml in 2.6% of myoma uteri, in 2.4% of benign ovarian tumors and 68.0% of ovarian cancers. Using a cut-off level of 35 U/ml, the results can be characterized by a 68.0% of sensitivity and 97.5% of specificity in detecting an ovarian cancer. Among 25 patients with ovarian cancer, 11 of 14 (78.6%) patients with serous cystadenocarcinoma, 4 of 6 (66.7%) patients with mucinous cystadenocarcinoma and 2 of 5 (40.0%) patients with endometrioid carcinoma had CA125 values greater than 35 U/ml. In relation to a higher tumor stage, there was an increasing incidence of elevated levels of CA125. As a result, it is likely that the measurement of CA125 is useful for early diagnosis of ovarian cancer.

협심증 환자에서 경피적 관동맥 확장술 후의 QT간격분산(QT Dispersion)의 변화

최일준,이일수,이상곤,홍명기,박성욱,박승정,김유호 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.9

Anti-inflammatory effect of polyphenol-rich extract from the red alga Callophyllis japonica in lipopolysaccharide-induced RAW 264.7 macrophages

Ryu, BoMi,Choi, Il-Whan,Qian, Zhong-Ji,Heo, Soo-Jin,Kang, Do-Hyung,Oh, Chulhong,Jeon, You-Jin,Jang, Chul Ho,Park, Won Sun,Kang, Kyong-Hwa,Je, Jae-Young,Kim, Se-Kwon,Kim, Young-Mog,Ko, Seok-Chun,Kim, G The Korean Society of Phycology 2014 ALGAE Vol.29 No.4

Despite the extensive literature on marine algae over the past few decades, a paucity of published research and studies exists on red algae. The purpose of this study was to evaluate the potential therapeutic properties of the ethanol extract of the red alga Callophyllis japonica against lipopolysaccharide (LPS)-stimulated macrophage inflammation. The C. japonica extract (CJE) significantly inhibited the nitric oxide (NO) production and the induced dose-dependent reduction of the protein and mRNA levels of inducible nitric oxide synthase and cyclooxygenase-2. Additionally, the CJE reduced the mRNA levels of inflammatory cytokines, including tumor necrosis factor-${\alpha}$, interleukin (IL)-$1{\beta}$, and IL-6. We investigated the mechanism by which the CJE inhibits NO by examining the level of mitogen-activated protein kinases (MAPKs) activation, which is an inflammation-induced signaling pathway in macrophages. The CJE significantly suppressed the LPS-induced phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase and p38 MAPK. Taken together, the results of this study demonstrate that the CJE inhibits LPS-induced inflammation by blocking the MAPK pathway in macrophages.

만경강의 수질 오염도 조사연구

최창진,유일수,황은희 圓光大學校 基礎自然科學硏究所 1986 基礎科學硏究誌 Vol.5 No.1

上關 저수지로부터 흘러 내려오는 맑은 물이 完山橋와 西新橋(〔A〕지점)를 지나면서 전주시민의 생활하수에 의하여 오염되어 흐르다가 전주 공업단지 폐수에 의하여 오염이 증가 되었다. 그러한 결과로 全州川과 전주 공업단지 폐수가 合流되는 〔D〕지점부터 全州川과 高山川이 合流되는 〔E〕지점 사이에서 水質汚染이 심하게 나타나고 있다. 全州川과 高山川의 맑은 물이 合流되는 〔E〕지점에서부터 水質汚染이 급격히 低下되고 있으며 만경강과 이리 공업단지 폐수가 合流되는 〔G〕와 〔H〕지점에서 수질오염은 加重되어 西海로 흘러가게 된다. 이와같은 결과로 볼때 만경강 수질오염의 主要因인 전주 공업단지 폐수와 이리 공업단지 폐수에 의하여 날로 오염이 심화되는 것을 알 수 있었다. An investigation on the water quality of the Mankyung river was carried out from March to september in 1984. The pollution levels of metals such as Pb, Cu and Cd were remarkably indicated high values at sites 〔C〕and 〔G〕. The values of BOD and COD were 30.1-468.4 ppm, 28.1-617.0 ppm, respectively and were serious. It is found that pH, SS, DO and Fe values of the river are 6.9-7.3ppm, 353-1322ppm, 2.8-6.7ppm and 1.29-9.226ppm, respectively. Those values were higher than values permitted by the environmental standards of the government. In conclusion that Mankyung river was being contaminated mainly by the waste water from the plants located at Jeon-ju Industrial Area and at Iri Industrial Area.

N-Arylnortropinone 유도체의 합성연구

李龍均,朴유미,鄭大一,金寅植,朴鍾勳,盧信愛,鄭逸守,朴敏洙 東亞大學校附設基礎科學硏究所 1998 基礎科學硏究論文集 Vol.15 No.1

Tropinone 화합물들은 색다른 고리계의 존재로 아주 오래전부터 약리학적으로 매우 흥미로운 연구과제로 주목되어 최근에 그들의 합성법,?? 입체적 구조분석?? 그리고 약리학적인 연구??가 활발히 진행되고 있다. Tropinone 1은 흔히 마약으로 알려져 있는 cocaine 2, 소염작용과 항경련성 작용 및 심장박동수를 조절 등 다양한 약리작용을 하는 tropane spirohy-dantoin ?? 그리고 안과질환을 검사 할 때 눈의 동공을 확장시키는 데 사용하는 atropine ??등을 합성하는 데 중요한 중간체이다. ??????????? Trigo, G, G등 ??은 aliphatic amine과 succinic aldehyde를 acetonedicarboxylic acid와 반응하여 nortropane 유도체를 합성하였으며, 그 후 [3+2] nitrone cycloaddition? 과 [3+4] cyclocoupling? 을 거치는 tropane alkaloid의 새로운 합성법이 개발되었다. 최근 lzquier M. L. 등¹은 acetonedicarboxylic acid를 사용하여 1차 지방족 amine과 succinic aldehyde대신 2,5-dimethoxytetrahydrofuran을 반응시켜 N-alkyl nortropinone 유도체를 합성하였다. 그러나 일반적으로 빙초산 속에서 amine과 2,5-dimethoxytetrahydrofuran을 반응시키면 pyrrole 유도체가 합성되어진다.?? 이러한 사실은 분명히 반응조건(예, 산, 온도)에 따른 다양한 화학이 존재한다고 볼 수 있다. 따라서 우리는 반응조건, 즉 산의 변화 및 온도 변화에 의한 amine과 2,5-dimethoxytetrahydrofuran의 반응을 자세하게 검토하면서 새로운 N-arylnortropinone 유도체를 합성하고자 한다.

그람양성구균에 대한 Teicoplanin과 Vancomycin의 시험관내 항균력

최태열,김경숙,전용관,서일혜,김정욱,이웅수,안정열,김홍석,정재용,최효선,김덕언,유진우 대한감염학회 1994 감염 Vol.26 No.1

An increasing frequency of methicillin resistant S. aureus(MRSA), methicillin resistant coagulase negative staphylococci(MRCNS) and Enterococcal infection have been observed in recent years. Teicoplanin is a new glycopeptide antibiotic obstained from the Actinoplanes teicomycetius. The molecular structure and spectrum of antimicrobial activity of teicoplanin is simillar to those of vancomycin, and has been reported to have an excellent in vitro and in vivo effect against various gram-positive infections. Therefore, we evaluated the in vitor susceptibility of gram positive cocci, such as, S. aureus, coagulase negative Staphylococci(CNS), and Enterococci to teicoplanin and vancomycin. The total 253 strains consisted of MSSA(40), MRSA(53), MSCNS(47), MRCNS(48), and Enterococci(65). They were assayed by disc diffusion and agar dilution. During the study, 57% of S. aureus and 49% of CNS showed resistance to methicillin. The inhibitory diameter of teicoplanin was 15-20mm in MSSA, 12-19mm in MRSA, 13-24mm in MSCNS, 11-23mm in MRCNS, and 15-22mm in Enterococci respectively, and showed sensitivity in all but 8 strains(3.2%). The range of the minimum inhibitory concentration (MIC) of teicoplanin to MSSA, MRSA, MSCNS, MRCNS and Enterococci were 9.12-2.0㎍/ml, 0.25-2.0㎍/ml, & 0.25-32㎍/ml, 0.12-1.0㎍/ml respectively. One case of S. haemolyticus was resistant to teicoplanin (32㎍/ml) by the agar dilution method. Eight minor (3.2%) and one major(0.4%) error was observed when the MIC and disk diffusion data were correlated with teicoplanin. As for vancomycin the inhibitory diameter was 17-21mm in MSSA, 15-21mm in MRSA, 18-26mm in MSCNS, 18-25mm in MRCNS, and 16-22mm in Enterococci respectively. The range of the MIC of vancomycin to MSSA, MRSA, MSCNS, MRCNS, and Enterococci were 0.25-1.0㎍/ml, 0.25-4.0㎍/ml, 0.5-2.0㎍/ml and 0.5-2.0㎍/ml respectively. One minor error (0.4%) was seen with the vancomycin disk. The MIC90 of MSSA and MRSA exhibited the same results in teicoplanin (1.0㎍/ml, 1.0㎍/ml), and vancomycin(2.0㎍/ml, 2.0㎍/ml). MSCNS and MRCNS exhibited greater MIC90 with teicoplanin(4.0㎍/ml, 8.0㎍/ml) than vancomycin(2.0㎍/ml, 2.0㎍/ml). Incontrase Enterococci were more susceptible to teicoplanin(0.5㎍/ml) than to vancomucin (2.0㎍/ml). Results from this analysis indicated that both teicoplanin and vancomycin were very excellent for gram positive infections, especially those resistant to methicillin.

Characterization of age‐associated exhausted CD 8 ⁺ T cells defined by increased expression of Tim‐3 and PD ‐1

Lee, Kyoo‐,A,Shin, Kwang‐,Soo,Kim, Ga‐,Young,Song, You Chan,Bae, Eun‐,Ah,Kim, Il‐,Kyu,Koh, Choong‐,Hyun,Kang, Chang‐,Yuil John Wiley and Sons Inc. 2016 Aging Cell Vol.15 No.2

<P><B>Summary</B></P><P>Aging is accompanied by altered T‐cell responses that result in susceptibility to various diseases. Previous findings on the increased expression of inhibitory receptors, such as programmed cell death protein 1 (PD‐1), in the T cells of aged mice emphasize the importance of investigations into the relationship between T‐cell exhaustion and aging‐associated immune dysfunction. In this study, we demonstrate that T‐cell immunoglobulin mucin domain‐3 (Tim‐3), another exhaustion marker, is up‐regulated on aged T cells, especially CD8<SUP>+</SUP> T cells. Tim‐3‐expressing cells also produced PD‐1, but Tim‐3<SUP>+</SUP>PD‐1<SUP>+</SUP>CD8<SUP>+</SUP> T cells had a distinct phenotype that included the expression of CD44 and CD62L, from Tim‐3<SUP>−</SUP>PD‐1<SUP>+</SUP> cells. Tim‐3<SUP>+</SUP>PD‐1<SUP>+</SUP>CD8<SUP>+</SUP> T cells showed more evident properties associated with exhaustion than Tim‐3<SUP>−</SUP>PD‐1<SUP>+</SUP>CD8<SUP>+</SUP> T cells: an exhaustion‐related marker expression profile, proliferative defects following homeostatic or TCR stimulation, and altered production of cytokines. Interestingly, these cells produced a high level of IL‐10 and induced normal CD8<SUP>+</SUP> T cells to produce IL‐10, which might contribute to immune dysregulation in aged mice. The generation of Tim‐3‐expressing CD8<SUP>+</SUP> T cells in aged mice seems to be mediated by encounters with antigens but not by specific infection, based on their high expression of CD49d and their unbiased TCR Vβ usage. In conclusion, we found that a CD8<SUP>+</SUP> T‐cell population with age‐associated exhaustion was distinguishable by its expression of Tim‐3. These results provide clues for understanding the alterations that occur in T‐cell populations with age and for improving dysfunctions related to the aging of the immune system.</P>

Deep resequencing of 131 Crohn's disease associated genes in pooled DNA confirmed three reported variants and identified eight novel variants

Hong, Sung Noh,Park, Changho,Park, Soo Jung,Lee, Chang Kyun,Ye, Byong Duk,Kim, You Sun,Lee, Seungbok,Chae, Jeesoo,Kim, Jong-Il,Kim, Young-Ho BMJ Publishing Group Ltd 2016 Gut Vol.65 No.5

<P>Objective Genome wide association studies (GWAS) and meta-analyses for Crohn's disease (CD) have not fully explained the heritability of CD, suggesting that additional loci are yet to be found and that the known loci may contain high effect rare risk variants that have thus far gone undetected by GWAS. While the cost of deep sequencing remains too high to analyse many samples, targeted sequencing of pooled DNA samples allows the efficient and cost effective capture of all variations in a target region. Design We performed pooled sequencing in 500 Korean CD cases and 1000 controls to evaluate the coding exon and 50 and 30 untranslated regions of 131 CD associated genes. The identified genetic variants were validated using genotyping in an independent set of 500 CD cases and 1000 controls. Results Pooled sequencing identified 30 common/low single nucleotide variants (SNVs) in 12 genes and 3 rare SNVs in 3 genes. Our results confirmed a significant association of CD with the following previously reported risk loci: rs3810936 in TNFSF15 (OR= 1.83, p< 2.2x10(-16)), rs76418789 in IL23R (OR= 0.47, p= 1.14x10(-8)) and rs2241880 in ATG16L1 (OR= 1.30, p= 5.28x10(-6)). In addition, novel loci were identified in TNFSF8 (rs3181374, OR= 1.53, p= 1.03x10(-14)), BTNL2 (rs28362680, OR= 1.47, p= 9.67x10(-11)), HLA-DQA2 (rs3208181, OR= 1.36, p= 4.66x10(-6)), STAT3 (rs1053004, OR= 1.29, p= 2.07x10(-5)), NFKBIA (rs2273650, OR= 0.80, p= 3.93x10(-4)), NKX2-3 (rs888208, OR= 0.82, p= 6.37x10(-4)) and DNAH12 (rs4462937, OR= 1.13, p= 3.17x10(-2)). A novel rare SNV, rs200735402 in CARD9, was shown to have a protective effect (OR= 0.09, p= 5.28x10(-5)). Conclusions Our deep resequencing of 131 CD associated genes confirmed 3 reported risk loci and identified 8 novel risk loci for CD in Koreans, providing new insights into the genetic architecture of CD.</P>