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        Inhibition of ERK1/2 by silymarin in mouse mesangial cells

        Cha Kyung Youn,Sung Il Cho,Min Young Lee,Young Jin Jeon,Seog Ki Lee 대한생리학회-대한약리학회 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.1

        The present study aimed to show that pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-1β] synergistically induce the production of nitric oxide (NO) production in mouse mesangial cells, which play an important role in inflammatory glomerular injury. We also found that co-treatment with cytokines at low doses (TNF-α; 5 ng/ml, IFN-γ; 5 ng/ml, and IL-1β; 1.25 U/ml) synergistically induced NO production, whereas treatment with each cytokine alone did not increase NO production at doses up to 100 ng/ml or 50 U/ml. Silymarin, a polyphenolic flavonoid isolated from milk thistle (<i>Silybum marianum</i>), attenuates cytokine mixture (TNF-α, IFN-γ, and IL-1β)-induced NO production. Western blot and RT-PCR analyses showed that silymarin inhibits inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner. Silymarin also inhibited extracellular signal-regulated protein kinase-1 and -2 (ERK1/2) phosphorylation. Collectively, we have demonstrated that silymarin inhibits NO production in mouse mesangial cells, and may act as a useful anti-inflammatory agent.

      • SCIESCOPUSKCI등재

        Inhibition of ERK1/2 by silymarin in mouse mesangial cells

        Youn, Cha Kyung,Cho, Sung Il,Lee, Min Young,Jeon, Young Jin,Lee, Seog Ki The Korean Society of Pharmacology 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.1

        The present study aimed to show that pro-inflammatory cytokines [tumor necrosis factor (TNF)-${\alpha}$, interferon (IFN)-${\gamma}$, and interleukin (IL)-$1{\beta}$] synergistically induce the production of nitric oxide (NO) production in mouse mesangial cells, which play an important role in inflammatory glomerular injury. We also found that co-treatment with cytokines at low doses (TNF-${\alpha}$; 5 ng/ml, IFN-${\gamma}$; 5 ng/ml, and IL-$1{\beta}$; 1.25 U/ml) synergistically induced NO production, whereas treatment with each cytokine alone did not increase NO production at doses up to 100 ng/ml or 50 U/ml. Silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), attenuates cytokine mixture (TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$)-induced NO production. Western blot and RT-PCR analyses showed that silymarin inhibits inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner. Silymarin also inhibited extracellular signal-regulated protein kinase-1 and -2 (ERK1/2) phosphorylation. Collectively, we have demonstrated that silymarin inhibits NO production in mouse mesangial cells, and may act as a useful anti-inflammatory agent.

      • 비용종 상피세포와 섬유아세포 동시배양 모델에서 시토카인의 발현

        김성완,조중생,박재경,이건희,차창일 WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2007 東西醫學硏究所 論文集 Vol.2007 No.-

        Background and Objectives: Nasal polyposis is a chronic inflammatory disease characterized histologically by edematous fluid with sparse fibrous cells, few mucous glands and proliferation of stromal and epithelial cells. There have been many studies done separately about epithelial cells, fibroblasts, and other inflammatory cells in nasal polyps. However, there is no usable study model for the cell-to-cell interaction. Therefore, we tried to make a new model for the study of nasal polyp by coculture of epithelial cells and fibroblasts. Subjects and Method: Nasal polyp was collected during endoscopic sinus surgery. Almost half of them were used for epithelial cell culture and the remaining portion was used for fibroblast culture in the same polyp. Using a transwell insert fibroblasts were placed in the bottom and epithelial cells were placed on the insert respectively. RNA were isolated both from cpithelial cells and fibroblasts of 12,24, and 48 hours' coculture. The expressions of IL-8,IL-6, and eotaxin from coculturcd cells were compared with cells that were cultured alone by semiquantitative RT-PCR. Results: IL-8 was highly expressed in fibroblasts than in epithelial cells, especially in cocultured cells. The expression of IL-6 in fibroblasts was much higher than in epithelial cells, especially in cocultured fibroblasts. Eotaxin is weakly expressed in fibroblasts but not in epithelial cells. Conclusion : These findings indicate that cocultured cells show different expression of the mRNA of various cytokines compared with cultured cells alone. And this coculture system may be more ideal than the mono-cell culture system for the study of cell-to-cell interactions and to reveal the pathogenesis of oasal polyposis.

      • 상악골 확장과 재발에 관한 연구

        이영일,차경석 단국대학교 치의학연구소 1990 논문집 Vol.2 No.-

        This research was carried out in order to study the effects of Rapid Maxillary Expansion on maxilla and it's surrounding skeletal structures. The sample for this study consists of 14 patients who were in retention period after rapid maxillary expansion. Following results were obtained after performing comparative analysis of cephalograms taken before and after rapid maxillary expansion. 1. In almost every cases, inferior displacement of palatal planes with concurrent changes in their inclination were observed. 2. Changes in the inclination of palatal plane can be categorized into inferiorly inclined group, superiorly inclined group and constant group in relation to the states before rapid masillary expansion. 3. Decrease in <Se-FMN/PMV and increase in <Se-FMN-A were evident in the superiorly inclined group and vice versa for the inferiorly inclined group.

      • SCOPUSSCIEKCI등재

        상악골 확장과 재발에 관한 연구

        이영일,차경석 대한치과교정학회 1991 대한치과교정학회지 Vol.21 No.2

        This research was carried out in order to study the effects of Rapid Maxillary Expansion on maxilla and it's surrounding skeletal structures. The sample for this study consists of 14 patients who were in retention period after rapid maxillary expansion. Following results were obtained after performing comparative analysis of cephalograms taken before and after rapid maxillary expansion. 1. In almost every cases, inferior displacement of palatal planes with concurrent changes in their inclination were observed. 2. Changes in the inclination of palatal plane can be categorized into inferiorly inclined group, superiorly inclined group and constant group in relation to the states before rapid maxillary expansion. 3. Decrease in < Se-FMN/PMV and increase in < Se-FMN-A were evident in the superiorly inclined group and vice versa for the inferiorly inclined group.

      • KCI등재

        위탁급식전문업체 인증제도 도입을 위한 급식운영 평가 모형 기준항목 선정

        양일선,박문경,차진아,이경태,박상용 한국조리과학회 2004 한국식품조리과학회지 Vol.20 No.3

        The foodservice industry is changing more and more from on-site foodservice management to contract foodservice management. However there are differences according to the level of management and operation of contract foodservice management company (CFMC), The necessity of certification on CFMC is increasing to enable fair discrimination of CFMC among most clients that want to contract with CFMC. This study was performed to identify the foodservice operation evaluation model's criteria items for certifying CFMC. The analysis research methods included literature review, content analysis, individual interview, Delphi technique, and brain storming. First, the following infrastructure items were prepared in the contractor's viewpoint: procurement, transparency of operation, menu development and operation system, nutrition service system, professional employee education, sanitation and safety management system, customer satisfaction system, facility system, management information system (MIS), business and economics. Second, the evaluation criteria required by the contractor on the client's view point was similar to school foodservice, hospitalfoodservice, and business andindustry foodservice except extraordinary items of field. Third, evaluation criteria and detail categories and items were identified such as financial focus, customer focus, process focus, human focus, and renewal and development by grafting on intellectual capital evaluation methodology for CFMC.

      • SCOPUSSCIEKCI등재

        한국인 2급 1류 부정교합자의 FHI (Facial Height Index)에 영향을 미치는 요소에 관한 두부방사선 계측학적 연구

        박영일,이진우,차경석 대한치과교정학회 1996 대한치과교정학회지 Vol.26 No.4

        안모의 수직적 부조화는 안면의 전방 고경 요소와 후방 고경 요소 사이의 상관 관계에 따라 결정되는 것이므로, 전하안면 고경에 대한 후하안면 고경의 비인 FHI에 따라 수직적 control이 치료 성공의 관건인2급 1류 부정 교합을 분류하고 FHI에 영항을 미치는 요소를 파악하여 치료의 지침으로 삼고자 본 연구를 시행하였다. 단국대학교 치과대학 교정과에 내원한 혼합치열기의 2급 1류 부정 교합자를 대조군의 FHI(평균 0.6999)의 1 S.D(0.25)를 기준으로 수직적으로 분류하였다. 임상적으로 수직적 부조화에 영향을 미칠 것으로 사료되었던 상악 제 1 재 구치 치조 교경, 구치간 각도, 구개평면 기울기, 하악지 기울기 등의 영향을 검증하고, 만약 영향을 미치지 않는다면 어느 요소가 FHI에 영향을 미치는가 알아보고자 하였으며, 각 군간에 골격적 양상을 알아보고자 하여 다음의 결론을 얻었다. 2급 1류 부정 교합자의 FHI에 주로 기여하는 요소로 구개 평면과 하악 평면 사이의 경사도이고, RH, ID의 순으로 나타났으며, 구개 및 하악 평면의 독립적인 경사도 보다는 상호 경사도가 중요하게 나타났다. 2급 1류 부정 교합의 양상은 FHI에 따라보면, Low group은 상악이 전돌되고 하악지의 발육이 아주 강하고 하악체의 길이 및 전후방 위치는 정상이다. Normo group은 상악은 약간 전돌되고 하악지의 발육이 정상보다 약하고 하악이 다소 후방에 위치하고, High group은 상악은 정상위치이고 하악지 및 하악체의 발육이 제일 약하며 하악이 후방에 위치하는 것으로 나타났다. 2급 1류 부정 교합자의 각 군간 FHI를 결정짓는 요소를 보면 Low group은 MP-PP각이 아주 작고, ID는 정상군과 유사하나 RH가 아주 커서 FHI가 크게된다. Normo-group은 PP-MP각이 정상이고, ID는 정상군보다 약간 작고 RH가 정상군보다 작아 FHI가 정상비를 유지하였다. High group은 PP-MP각이 아주 크고 ID는 정상군과 유사하나 RH가 정상군보다 작아 FHI가 작았던 것으로 나타났다. Facial vertical dyscrepancies is decided on the relationship between the anterior vertical facial height and posterior vertical facial height. Thus this study was conducted to determine the factors that affect the FHI, and classify the Class II div.1, malocclusion, which success is dependent on the vertical control according to the FHI, which is the ratio of antero-inferior facial height, posterio-inferior facial height ratio, and to use this as a guideline for treatment. Angle between palatal plane and Mandibular plane were in the order of RH, ID. Thus showing that interrelated angle was more important than the independent angle of both, palatal plane and Mandibular plane. The tendency of Cl II div.1. Malocclusion according to FHI, showed the Low group to have Mx. protrusion, prominent development of Mn. ramus, and the Mn. body length and ant. post. position was normal. The Normo group showed slight protrusion of the Maxilla,. The development of the ramus was less than normal and the Mn. was in a slight retruded position. The High group showed the Mx. in a normal position, the development of the Mn. ramus and body was the lowest, and the Mn. was in a Posterior position. In observation of the factors affecting the FHI between each groups of Cl II div.1. malocclusion; In the Low group the MP-PP angle was very small, the ID was smililar to the normal group, but the RH was very large thus the FHI was increased. In the Normo group, the PP-MP angle was normal, ID was slightly smaller than the normal group and the RH was slightly smaller than the normal group, thus maintaining a normal FHI ratio. In the High group the PP-MP angle was very large, the ID was similar to the normal group, but the RH was smaller than the normal group thus the FHI was small.

      • SCOPUSKCI등재

        당뇨병 환자에서 혈장 Thrombin-Antithrombin Ⅲ 및 Plasmin-α_2-Plasmin Inhibitor 복합체의 임상적 의의

        김경욱,김은숙,정상수,윤수지,박우일,이준희,남수연,안철우,문병수,김경래,차봉수,송영득,임승길,이현철,허갑범 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.25 No.5

        연구배경:당뇨병 환자에서 혈액응고 및 섬유소용해 체계의 이상경향이 있어 그 결과로 여러 혈관합병증의 발생위험이 높다는 사실은 널리 알려져 있다. 그 기전은 아직 확실히 밝혀지지 않았으나, 고혈당으로 인한 혈장 단백질들의 비효소성 당화작용이나 산화성 스트레스로 인한 유리 라티칼 작용으로 응고항진이나 섬유소용해 활성의 저하를 유발하는 것으로 생각되고 있다. 최근 응고 및 용해인자와 그 억제자의 복합체들의 증가가 이 상태를 비교적 예민하게 반영한다고 알려져 있다. 방법:본 연구에서는 당뇨병 환자 101명과 정상 대조군 20명에서 혈장내 thrombin­antithrombin complex(TAT)와 plasmin­α₂­plasmin inhibitor complex(PIC)를 측정하여 비교하고, 당뇨병 환자에서 미세혈관 합병증과 대혈관합병증의 유무에 따른 차이와, 이미 혈관 질환의 위험인자로 알려져 있는 인자들간의 상관성을 알아보고자 하였다. 결과:1. 환자의 분포를 살펴보면 혈관합병증이 있는 군은 85명, 혈관합병증이 없는 군은 16명이었고, 평균연령은 각각 57.9±14.1세, 49.9±16.6세로 혈관 합병증이 있는 군에서 더 나이가 많았고, 체질량지수는 23.2±3.4㎏/㎡, 24.1±3.4㎏/㎡로 두 군간 유의한 차이는 없었다. 또 두 군간의 혈압 및 HbA1c, 공복혈당 및 인슐린과 C­peptide, 총 콜레스테롤, 중성지방, HDL­콜레스테롤, Lp⒜는 유의한 차이가 없었고, 미세혈관합병증이 있는 군에서 당뇨병의 유병기간이 길었다. 2. TAT 및 PIC의 농도는 정상 대조군에서는 2.8±1.2 ng/mL, 240.4±69.7 ng/mL이었고, 당뇨병 환자군에서는 9.5±22.6 ng/mL, 472.2±258.7 ng/mL이었다. TAT와 PIC 모두 당뇨병 환자군에서 정상 대조군에 비해 유의하게 증가되어 있었고(p<0.001), TAT/PIC ratio는 두 군간 차이가 없었다. 3. 당뇨병 환자의 혈관합병증에 따른 TAT 및 PIC, fibrinogen 농도는 합병증이 없는 군은 각각 4.1±2.4ng/mL, 362.2±272.0ng/mL, 322.7±102.4mg/mL으로 PIC와 fibrinogen의 증가를 보였으나, 연령을 보정한 후에는 통계학적 유의성은 없었다. 또 대혈관 합병증군에서는 각각 6.0±4.9 ng/mL, 507.4±321.6 ng/mL, 427.1±194.7 mg/dL이었으며 미세·대혈관 합병증군에서는 10.4±6.4 ng/mL, 484.8±269.7 ng/mL, 388.4±132.4 mg/dL으로 TAT의 증가를 보였으나 역시 연령을 보정한 후에는 통계학적 유의성은 없었다. 4. 미세혈관합병증군에서 HbA1c(>8%)가 높은 군의 PIC 농도가 유의하게 높았고(p=0.049), 대혈관합병증군에서 HbA1c(>8%)가 높은 군의 총 콜레스테롤 농도가 유의하게 높았다(p=0.042). 5. 총 당뇨병 환자군에서 PIC는 fibrinogen과 HbA1c와 양의 상관관계를, BMI와 음의 상관관계를 보였으며(r=0.47, 0.31,-0.25), 혈관 합병증이 없는 당뇨병 환자군에서만 TAT는 HbA1c와 양의 상관관계를 보였다(r=0.67). 결론:이상의 결과에서 혈장 TAT 및 PIC 농도는 당뇨병 환자에서 정상 대조군에 비해 의미있게 증가되어 있었고, 당뇨병 환자군에서는 연령의 증가와 유병기간이 혈액응고항진 및 용해의 장애에 큰 역할을 함을 알 수 있었으며, 총 당뇨병 환자군에 PIC와 HbA1c와 양의 상관관계를, BMI와 음의 상관관계를 보였으며 혈관 합병증이 없는 당뇨병 환자군에서만 TAT는 HbA1c와 양의 상관관계를 보였다. 따라서 당뇨병 환자에서 혈액응고 및 용해의 장애가 동반되어 있다고 볼 수 있으며, 혈장 TAT 및 PIC는 혈관합병증으로의 진행을 예측하는 지표로서 유용하리라 생각된다. 또 혈당조절정도와 상관성이 있으므로 혈당조절후에 추적검사를 시행하여 합병증의 예방이 가능한지 추후 연구가 필요하리라 생각된다. Background : Abnormality of coagulation and fibrinolystic system is known as a predisposing factor of vascular complication in diabetes. Although the pathogenesis is not well known, non-enzymatic glycation reaction and the increase in production of free radicals due to an increased oxidative stress may be linked to the hypercoagulibility and hypofibrinolytic activity. As indices of abnormality in coagulation and firinolysis in peripheral blood, plasma thrombin-antithrombin Ⅲ complex (TAT) and plasmin-α_2-plasmin inhibitor complex (PIC) were measured. The purpose of this study was to clarify whether hypercoagulability exists in diabetic patients with or without vascular complication. Methods : In our study, we measured plasma thrombin-antithrombin Ⅲ compelx (TAT) and plasmin-α_2-plasmin inhibit or complex (PIC) in 101 diabetic subjects and 20 controls. Comparing TAT and PIC levels in diabetic microvascular complication group, diabetic macrovascular complication group and controls, we examined correlation between risk factors associated with diabetic vascular complication. Results : 1. The group with diabetic vascular complication was older than group without complication. There was no significant difference in BMI, blood pressure, HbA_ic, blood sugar level, insulin, C-peptide, serum creatinine, total cholesterol, triglyceride, HDL-cholesterol, Lp (a) between two groups. The group with diabetic microvascular complication had longer duration of diabetes. 2. Concentration of TAT and PIC were 2.8±1.2 ng/ mL, 240.4±69.7 ng/ mL in controls and 9.5±22.6 ng/ mL, 472.2±258.7 ng/ mL in diabetic patients, respectively. TAT and PIC were significantly higher in diabetic patients than in control (p<0.001). But TAT/PIC ratio was no significant difference between two groups. 3. In diabetic patients, concentration of TAT and PIC and fibrinogen were respectively 4.1±2.4 ng/ mL, 362.2±272.0 ng/ mL, 322.7±102.4 mg/ dL in group without vascular complication and 5.3±4.1 ng/ mL, 529.5±258.7 ng/ mL, 374.9±106.2 mg/ dL in group with microvascular complication, which group had increase in PIC and Fibrinogen but no significance after correction of age. Concentration of TAT and PIC and Fibrinogen were 60.±4.9 ng/ mL, 507.4±321.6 ng/ mL, 427.1±194.7 mg/ dL in macrovascular complication, and 10.4±6.7 mg/ mL, 484.8±269.7 ng/ mL, 388.4±132.4 mg/ dL in combined vascular complication which group showed increase of TAT but also had no significant increase after correction of age. 4. In diabetic microvascular complication patients, group of high HbA_1c (>8%) (p=0.049) had significant high PIC concentration. In diabetic macrovascular complication patients, group of high HbA_1c (>8%) (p=0.042) had significant high total cholesterol concentration. 5. In all diabetic patients, PIC was positively correlated with fibrinogen and HbA_1c and negatively correlated BMI (r=0.47, 0.31, -0.25). Only in daibetic patients without angiopathy, TAT was positively correlated with HbA_1c (r=0.67). Conclusion : In this study, plasma TAT and PIC concentration significantly increased in diabetic patients compared with controls, and PIC was increased in group with microvascular complication, TAT were increased in group with combined micro macrovascular complication. However, there was no significance relationship existed when correctinf for age. PIC was correlated with HbA_1c. TAT was correlated with HbA_1c only in the group without angiopathy. Abnormality of coagulation and fibrinolysis were combined in diabetes, plasma TAT and PIC can be used as an index of vascular complication. Also we found the correlation with the degree of the blood glucose control. Therefore we need follow up study for the possibility of prevention of vascular complication after controlling the blood glucose to age-matched patients (J Kor Diaabetes Asso 25:354~363, 2001).

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