Hirsutenone reduces deterioration of tight junction proteins through EGFR/Akt and ERK1/2 pathway both converging to HO-1 induction

( Geom Seog Seo ),( Wen Yi Jiang ),( Pil Hoon Park ),( Dong Hwan Sohn ),( Jae Hee Cheon ),( Sung Hee Lee ) 영남대학교 약품개발연구소 2014 영남대학교 약품개발연구소 연구업적집 Vol.24 No.0

Oxidative stress-induced disruption of epithelial tight junctions (TJ) plays a critical role in the pathogenesis of intestinal disorders, including inflammatory bowel disease (IBD). The current study investigated the protective effect of hirsutenone against disruption of the intestinal barrier in vitro and in a mouse model of colitis. Caco-2 cells were stimulated with tert-butyl hydroperoxide (t-BH). Hirsutenone prevented the t-BH-induced increase in permeability by inhibiting the reduction in zonula occludens-1 (ZO-1) expression, and rapidly stimulated tyrosine phosphorylation of the epidermal growth factor receptor (EGFR). Hirsutenone-mediated protection against the loss of ZO-1 depends on the activation of both ERK1/2 and Akt signaling pathways. Interestingly, hirsutenone-mediated activation of Akt, but not ERK1/2, signaling was EGFR-dependent. Hirsutenone increased heme oxygenase-1 (HO-1) expression through both EGFR/Akt- and ERK1/2-dependent pathways, contributing to the protective effects against TJ dysfunction. Colitis was induced in mice by intrarectal administration of 2,4,6,-trinitrobenzene sulfonic acid (TNBS). Hirsutenone administration improved the clinical parameters and tissue histological appearance, increased HO-1 expression, attenuated reduction of ZO-1 and occludin mRNA, and promoted BrdU incorporation in the colonic epithelium of TNBS-treated mice. Taken together, our results demonstrate that hirsutenone reverse disordered intestinal permeability by activating EGFR/Akt and ERK1/2 pathways, which are involved in the regulation of HO-1 expression. These findings highlight the potential of hirsutenone for clinical applications in the treatment of IBD.ⓒ2014 Elsevier inc All rights reserved.

Original Articvle : The Prevalence of Erosive Esophagitis Is Not Significantly Increased in a Healthy Korean Population -Could It Be Explained?: A Multi-center Prospective Study

( Geom Seog Seo ),( Byung Jun Jeon ),( Jin Soo Chung ),( Young Eun Joo ),( Gwang Ha Kim ),( Gwang Ho Baik ),( Dae Yong Kim ),( Jeong Eun Shin ),( Heung Up Kim ),( Hyun Kyung Park ),( Nayoung Kim ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2013 Journal of Neurogastroenterology and Motility (JNM Vol.19 No.1

Background/Aims Researches on the potential risk factors for the development of erosive esophagitis have been conducted extensively, however, the results are conflicting. The aim of this multicenter study was to identify the prevalence rate and risk factors of erosive esophagitis and their interactions with residency status. Methods A total of 4,023 eligible subjects at 8 tertiary health care centers were evaluated using questionnaires, laboratory tests and endoscopy. Univariate and multivariate analyses were conducted to identify independent risk factors for erosive esophagitis. Results The prevalence rate of reflux esophagitis was 8.8%. Los Angeles grade A was common type of erosive esophagitis. Residence in a large urban areas was negatively associated with the development of erosive esophagitis (OR, 0.60; 95% CI, 0.40-0.90). The high body mass index (≥ 25 kg/m2) was more frequent in residents of small and medium-sized cities than those in big cities (38.8% and 26.9%, respectively; P < 0.001). Seronegativity of Helicobacter pylori was associated with increased erosive esophagitis (OR, 1.91; 95% CI, 1.48-2.46). Triglyceride ≥ 150 mg/dL (OR, 1.65; 95% CI, 1.08-2.07), fasting glucose level ≥ 126 mg/dL (OR, 1.73; 95% CI, 1.06-2.81), and hiatal hernia (OR, 3.11; 95% CI, 1.87-5.16) were also associated with erosive esophagitis. Conclusions The prevalence rate of erosive esophagitis and its risk factors in this study were similar to the result of 8.0% of nationwide study in 2006. Residency and obesity are more important independent risk factors than H. pylori infection status for development of erosive esophagitis in Korea. These results suggest that the prevalence rate of erosive esophagitis in Korea might not increase as in the Western countries. (J Neurogastroenterol Motil 2013; 19:70-77).

Expression of Proteinase-Activated Receptor 2 in Ulcerative Colitis

( Geom Seog Seo ),( Sang Wook Kim ),( Kyo Sang Yoo ),( Young Woo Sohn ),( Tae Hyeon Kim ),( Suck Chei Choi ),( Yong Ho Nah ),( Ki Jung Yun ),( Jin A Kim ),( Young Mi Lee ) 대한소화기학회 2002 대한소화기학회 추계학술대회 Vol.2002 No.-

REVIEW : Clostridium difficile Infection: What`s New?

( Geom Seog Seo ) 대한장연구학회 2013 Intestinal Research Vol.11 No.1

Since 2000, Clostridium difficile infection has increased substantially in both hospital-acquired and community-acquired diarrhea, not only in North America but also in Europe. There was a steady increase in the incidence and severity of C. difficile infection over the past decade, associated with significantly higher morbidity and mortality. The major risk factors for C. difficile infection appear to be the use of new antimicrobial therapy, long-term hospitalization in old age and emerging hypervirulent strains, such as various ribotypes. Rapid and accurate diagnosis of C. difficile infection is necessary for appropriate treatment as well as reliable epidemiological data. Currently available treatment options are withdrawal of the suspected offending antibiotics and then treating patients with highly effective antibiotics for C. difficile. Multiple recurrence or acute fulminant C. difficile infection could be treated with fecal microbiota transplantation. Promising therapies for treating C. difficile infection should always be equipped with high efficacy and safety in the future. (Intest Res 2013;11:1-13)

Medicinal Chemistry : Heme oxygenase-1 promotes tumor progression and metastasis of colorectal carcinoma cells by inhibiting antitumor immunity

( Geom Seog Seo ),( Wen Yi Jiang ),( Jin Hua Chi ),( Hao Jin ),( Won Chul Park ),( Dong Hwan Sohn ),( Pil Hoon Park ),( Sung Hee Lee ) 영남대학교 약품개발연구소 2015 영남대학교 약품개발연구소 연구업적집 Vol.25 No.-

Heme oxygenase-1 (HO-1) is upregulated in colorectal carcinoma (crc) cells.However, the role of HO-1 in the metastatic potential of CRC remains to be elucidated.In this study, we inves tigated the potential of HO-1 to control the antitumor immunity of CRC.Intercellular adhesion molecule-1(ICAM-1)plays an important role in the immune surveillance system. Hemin-induced HO-1 expression suppressed the expression of ICAM-1 in human CRC cells. HO-1 regulated ICAM-1 expression via tristetraprolin, an mRNA-binding protein, at the posttranscriptional level in CRC cells. The upregulated HO-1 espression in CRC cells markedly decreased the adhesion of peripheral blood mononuclear lymphocytes (PBMLs) to CRC cells and PBML-mediated cytotoxicity against CRC cells. Production of CXCL10, an effector T cell-recruiting chemokine, was significantly reduced by the increased HO-1 expression. The expression of the CXCL10 receptor, CKCR3, decreased significantly in PBMLs that adhered to CRC cells. HO-1 expression correlated negatively, although nonsignificantly, with ICAM-1 and CXCL10 expression in xenograft tumors. Taken together, our data suggest that HO-1 expression is functionally linked to the mediation of tumor progression and metastasis of CRC cells by inhibiting antitumor immunity.

Transactions : Dyeability and Colorfastness of Knitted Fabrics with Natural Dye Pinux(TM) (Part 1)

( Geom Bong Wang ),( Kyung Hun Song ) 한국의류학회 2011 한국의류학회지 Vol.35 No.12

Dyeability and colorfastness of the blended knits of cotton/rayon (40/60; C/R) and wool/tencel (10/90; W/T) are examined using the natural dyestuff (Pinux (TM)) manufactured from Pinus radiata pine bark extract. In addition, pre-treatments (such as bleaching, mercerization and cationization) are performed to improve dyeability and colorfastness. The Pinux(TM) powder dyestuffs produced by Pinux Co., Ltd. are used as dyestuffs and their properties are examined for dyeing concentration (0.5-2% (owb)), dyeing time (30-120 minutes) and dyeing temperature (30-90℃). Dyeability is evaluated with K/S value at 400nm, which is the maximum absorption wavelength for Pinux(TM). The results show the dyeability of W/T sample containing protein fiber with Pinux(TM) is superior to all cellulose fiber C/R. A concentration of dyestuff greater than 1.5% (owb), dyeing time 120 minutes and dyeing temperature of 90℃ are the most optimized conditions. It shows that the dyeability of C/R and W/T samples are high in the condition of an acid-dyeing bath and that dyeability highly declined in alkaline bath due to the instability of the proanthocyanidin pigment. After analyzing the effect of bleaching, mercerizing and cationizing (as pre-treatments on dyeability) it was concluded that the dyeability of the C/R sample was enhanced by mercerization but no significant effect by cationization. However, the simultaneous treatment of cationizing and dyeing resulted in far improved dyeability compared to dyeing after cationizing pre-treatment. As for the W/T sample, the effect of cationization was more prominent than the C/R sample. Colorfastness to color changes in the control W/T sample was higher than that of C/R`s level 1-2, and it increased to Level 2 when bleaching pre-treatment was given and when a simultaneous cationizing treatment was adopted to the dyeing process. Colorfastness to light in W/T control sample resulted in Level 3 and further increased to an excellent Level of 4 with bleaching and simultaneous cationizing during dyeing process.

Identification of the polymorphisms in IFITM3 gene and their association in a Korean population with ulcerative colitis

Geom Seog Seo,최석채,Jeong Kun Lee,Ji In Yu,윤기중,채수천 생화학분자생물학회 2010 Experimental and molecular medicine Vol.42 No.2

Interferons play critical roles in tumor pathogenesis by controlling apoptosis and through cellular anti-proliferative and differentiation activities. Interferon inducible transmembrane protein (IFITM) family genes have been implicated in several cellular processes such as the homotypic cell adhesion functions of IFN and cellular anti-proliferative activities. Expression levels of IFITM genes have been found to be up-regulated in gastric cancer cells and colorectal tumors. IFITM3 (also known as 1-8U) is a member of the IFITM family, and has been described as a key player in specification of germ cell fate. IFITM3 was first isolated from a genetic screen aimed at identifying genes involved in acquisition of germ cell competence. It has been proposed that epiblast cells have the highest expression of IFITM3 initiated germ cell specification and that homotypic association can discriminate germ cells from their somatic neighbors. In an attempt to better understand the genetic influences of IFITM3 on ulcerative colitis, we have identified possible variation sites and single nucleotide polymorphisms (SNPs) through two exons and their boundary IFITM3 intron sequences including the ∼2.1 kb promoter regions. To determine whether or not these IFITM3 SNPs are associated with susceptibility to ulcerative colitis, frequencies of the genotype and allele of IFITM3 polymorphisms were analyzed on genomic DNAs isolated from patients with ulcerative colitis and from healthy controls. We also investigated the haplotype frequencies constructed by these SNPs in both groups. In this study, we also showed that expression level of IFITM3 mRNA was significantly higher in tissues of the ileum and cecum of the digestive system. We identified a total of seven SNPs and multiple variation regions in the IFITM3 gene. The genotype frequency of the g.-204T>G polymorphism in patients with ulcerative colitis was significantly different from that of the control group. Our results strongly suggest that polymorphisms of the IFITM3 gene may be associated with susceptibility to ulcerative colitis.

The Korean Society of Gastroenterology & SIDDS 2034 : Slide Session ;K-LG-05 : Lower GI Tract ; Heme Oxygenase-1 Enhances Metastatic Properties of Colon Cancer Through Cancer Cell Escape from Immunological Recognition and Decrease Effector T Cells Recruit

( Geom Seog Seo ),( Suck Chei Choi ),( Wen Yi Jiang ),( Hao Jin ),( Jin Hua Chi ),( Sung Hee Lee ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: A growing body of evidence indicates that HO-1 activation may play a role in carcinogenesis and can potently infi uence the growth and metastasis of tumors.In this study, we investigated the metastatic potential of HO-1 focused on modulation of immunogenicity in colon cancer cells. Methods: By using colon cancer cell lines, HT-29 and Caco-2, the effect of HO-1 on intercellular adhesion molecule-1 (ICAM-1) expression, cell matrix attachment and cancer cell immunogenicity were investigated. In addition, we determined whether the expression of effector T cells (Teff)- and regulatory T cells (Treg)-recruiting chemokines are regulated by HO-1 in HT-29 cells. Results: HO-1 induction by treatment with hemin down-regulated ICAM-1 protein expression in colon cancer cells in dose-dependent way, whereas hemin did not reduce ICAM-1 mRNA expression. HO-1 decreases ICAM-1 expression via tristetraprolin (TTP), an mRNA-binding protein that destabilizes ICAM-1 mRNA. The adhesion of peripheral blood mononuclear lymphocytes (PBMLs) to HT-29 and HT-29 cytotoxicity during co-culture with PBMLs were remarkably decreased by treatment with hemin. In addition, Teff-recruiting chemokines, CCL5 and CXCL10 expressions signifi cantly decreased by hemin in HT-29 cells, whereas hemin did not infi uence CCL22 expression, which is Treg-recruiting chemokine. IFN-γ-induced CXCL10 mRNA expression and protein secretion was also inhibited by hemin in a dose-dependent manner. In contrast, CXCL10 mRNA and protein secretion were up-regulated in HT-29 cells transfected withHO-1-specifi c siRNA, which potentiated IFN-γ-stimulation. Conclusions: The present study suggested that decreased ICAM-1 expression and Teff-recruiting chemokines expression by hemin contributes to cancer cell detach from the primary tumor mass and escape from immunological recognition and cytotoxicity by host effector cells, which may provide a mechanism of HO-1 in the tumor progression and metastasis of colon cancer.

Comparison of pediatric injury patterns before and during the COVID-19 pandemic in Korea: a retrospective study

( Geom Pil Nam ),( Woo Sung Choi ),( Jin-seong Cho ),( Yong Su Lim ),( Jae-hyug Woo ),( Jae Ho Jang ),( Jea Yeon Choi ) 대한외상학회 2023 大韓外傷學會誌 Vol.36 No.4

Purpose: The COVID-19 pandemic led to significant changes in the lifestyle patterns of children and affected the patterns of pediatric injuries. This study analyzed the changing patterns of pediatric injury overall and by age groups, based on the datasets before and during the COVID-19 pandemic. Methods: This study is based on the data of patients who presented with injuries at 23 hospital emergency departments participating in the Emergency Department-based Injury In-depth Surveillance (EDIIS) conducted by the Korea Disease Control and Prevention Agency. The surveillance data was categorized by injury mechanism, location, activity, and severity. We analyzed the injury patterns of pediatric patients aged 0 to 15 years. Subgroup analysis was conducted by age group in children aged 7 to 15 years, 1 to 6 years, and <1 year. Results: When comparing the COVID-19 pandemic period to the pre-COVID-19 period, the total number of pediatric patients with injuries decreased by 38.7%, while the proportions of in-home injuries (57.9% vs. 67.9%), and minor injuries (38.9% vs. 39.7%) increased. In the 7 to 15 years group, bicycle riding injuries (50.9% vs. 65.6%) and personal mobility device injuries (2.4% vs. 4.6%) increased. The 1 to 6 years group also showed an increase in bicycle accident injuries (15.8% vs. 22.4%). In the <1 year group, injuries from falls increased (44.5% vs. 49.9%). Self-harm injuries in the 7 to 15 years group also increased (1.6% vs. 2.8%). Conclusions: During the COVID-19 pandemic period, the overall number of pediatric injuries decreased, while injuries occurring at home and during indoor activities increased. Traffic accidents involving bicycles and personal mobility devices and self-harm injuries increased in the 7 to 15 years group. In the <1 year group, the incidence of falls increased. Medical and societal preparedness is needed so that we might anticipate these changes in the patterns of pediatric injuries during future infectious disease pandemics.

일부 대학생들의 흡연실태 조사

강점덕(Geom-Duk Kang),조은정(Eun-Jeong Cho) 한국안전교육학회 2001 한국안전교육학회지 Vol.4 No.1

Objectives : This study aims to investigate smoking patterns in college students and to give students smoker effective information. Methods : The sample of 140 male college students was questioned in andong science college from september 26 to 27, 2000. Results : Among the surveyed students 55.5% of 19 years old smoke habitually. It also shows that 48.9% of smoking students began smoking in high school. 10~20 number of cigarettes smoke a day was 43.3%. Relationship of student smoking to parent with smoker was 80.0%. When it comes to the family factors in smoking, religon of family member did not make any noticeable statistical differences. 75.6% of smoking students say that they will stop smoking, While the remaining 24.4% say that they will keep smoking. The reason of 50.0% to stop smoking is that smoking is bad for the health. Conclusions : We should make specific plan to keep smoking by simple curiosity from being developed into habitual smoking.