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).

Administration of tauroursodeoxycholic acid enhances osteogenic differentiation of bone marrow-derived mesenchymal stem cells and bone regeneration

Cha, Byung-Hyun,Jung, Moon-Joo,Moon, Bo-Kyung,Kim, Jin-Su,Ma, Yoonji,Arai, Yoshie,Noh, Myungkyung,Shin, Jung-Youn,Kim, Byung-Soo,Lee, Soo-Hong Elsevier 2016 Bone Vol.83 No.-

<P><B>Abstract</B></P> <P>It is known that osteogenic differentiation of mesenchymal stem cells (MSCs) can be promoted by suppression of adipogenesis of MSCs. We have recently found that the chemical chaperone tauroursodeoxycholic acid (TUDCA) significantly reduces adipogenesis of MSCs. In the present study, we examined whether TUDCA can promote osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMMSCs) by regulating Integrin 5 (ITGA5) associated with activation of ERK1/2 signal pathway and thereby enhance bone tissue regeneration by reducing apoptosis and the inflammatory response. TUDCA treatment promoted <I>in vitro</I> osteogenic differentiation of BMMSCs and <I>in vivo</I> bone tissue regeneration in a calvarial defect model, as confirmed by micro-computed tomography, histological staining, and immunohistochemistry for osteocalcin. In addition, TUDCA treatment significantly decreased apoptosis and the inflammatory response <I>in vivo</I> and <I>in vitro</I>, which is important to enhance bone tissue regeneration. These results indicate that TUDCA plays a critical role in enhancing osteogenesis of BMMSCs, and is therefore a potential alternative drug for bone tissue regeneration.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Tauroursodeoxycholic acid (TUDCA) promotes osteogenic differentiation of mouse bone marrow mesenchymal stem cells (mBMMSCs). </LI> <LI> TUDCA stimulates Integrin 5 (ITGA5) associated with activation of ERK1/2 signal pathway. </LI> <LI> TUDCA enhances bone tissue regeneration by the suppression of apoptosis and inflammatory response. </LI> <LI> TUDCA promotes bone tissue regeneration in mouse calvarial defects. </LI> <LI> Ursodeoxycholic acid (UDCA), which has a similar chemical structure to TUDCA, also increases bone regeneration. </LI> <LI> TUDCA is a useful pharmacological substitute for BMP-2, which is clinically available for bone tissue regeneration. </LI> </UL> </P>

SIMULTANEOUS DESCRIPTION OF STRONG AND WEAK H2 ADSORPTION SITES COEXISTING IN MOFs

MOON-HYUN CHA,MANH CUONG NGUYEN,KEUNSU CHOI,MINSUNG KIM,임지순 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2011 NANO Vol.6 No.3

We present a theoretical model capable of identifying multiple adsorption sites in a gas storage material with different binding energies and different amounts of adsorbed molecules. By applying this model to experimental data on the hydrogen storage in MOFs, we extract hydrogen adsorption properties of MOFs with coexisting strong and weak adsorption sites.

Cationic Liposome-Mediated p53 Gene Therapy in Liver Cancers: Result of Basic and Clinical Study

Moon,Young Ho,Kim,Byung Koo,Shim,Hyung Jin,Uhm,Tae Han,Cha,Sung Jae,Moon,Chul So,Moon,Woo-Chul,Kwak,Byung Kook,Gi,Young Jin,Lim,Hyun Mook,Yoo,Nam Sook,Lee,Chang Joon 가톨릭중앙의료원 가톨릭암센터 1998 암심포지움 Vol.- No.2

p53 is a prototype tumor suppressor gene, which plays key roles in regulation of cell cycle progression, apoptosis, DNA repair and maintenance of genomic stability. Experimental stydy study on p53 gene therapy for cancer have been widely tried and Success of adenovirus or retrovirus-mediated p53 gene therapy have been reported in patients with lung cancer and cancer of the head and neck. However, viral vector-mediated gene therapy may have demerits to be widely applied in human cancers. We herein have designed a cationic liposome-mediated p53 gene therapy and have studied its antitumor efficacy and safety in vitro, in vivo and in human patients with advanced liver cancers. We constructed and prepared a complex of plamid vector carrying cDNA of human wild type(WT) p53, cationic liposome (HECH : DOPE) and cationic polymer (polylysine) in sterile and endotoxin-free condition depending on the guideline of FDA and used this complex for in vitro and in vivo transfer oi WT p53 gene. In vitro administration of p53 gene to a variety of human cancer cells with point mutation or deletion of p53 in DNA dose of 1㎍ per ?? cells induced high level expression of WT p53 and p21/WAF1 as demonstrated by RT-PCR-Southern blot and Western blot, apoptosis as demonstrated by DNA electrophoresis, and significant decrease of viable cell numbers by 70.4 to 98.5%, whereas, administration of p53 gene in same condition to human cancer cells with WT p53 didn't induce either apoptosis or significant decrease of viable cell numbers. In vivo antitumor efficacy of p53 gene transfer was initially analyzed in sc,ip, subrenal capsular and intrahepatic xenograft model of human cancers with deletion of p53. Local, ip, or iv administration of p53 gene in DNA dose of 100㎍ daily for 5 to 10 days induced expression of WT p53 and p21 in tumor tissues, significant decrease of tumor volume (by 62.0 to 99.5%)and/or incidence of tumors, and complete suppression of metastasis. Intravenous administration of p53 gene in DNA dose of up to 12 mg/kg to rats didn't induce significant acute or sub-acute toxicity as demonstrated by survival body weight, laboratory studies, and histologic analysis of vital organs. Trans-hepatic arterial administration of p53 in DNA dose of 0.5 to 5 mg per kg induced expression of human WT p53 in rabbits liver and/or lung and didn't induce significant hepatic toxicity or systemic toxicity. Trans-hepatic arterial administration of p53 gene in DNA dose of 1 mg per kg induced significant decrease of tumor incidence (to 40%) and volume (to 0.4% of control) and suppression of metastasis of rabbits liver VX2 carcinoma which carry point mutation of p53. These results suggested that our cationic polyliposome-mediated p53 gene trasfer might be a promising treatment modality for human cancers which carry mutation of p53. Based on the results of basic research, we carried out a pilot study to investigate antitumor efficacy and safety of cationic liposome-mediated p53 gene therapy in patients with liver cancer. Patients whth advanced, primary (N=12) or metastatic (N=4) liver cancer who had failed conventional therapy underwent p53 gene therapy, of whom 12 showed mutation of p53. Patients with advanced liver cirrhosis or metastasis were also included in the study. Fifteen patients with advanced liver cancer who underwent hepatic angiography alone served as control. p53 gene was administered in complex with HECH : DOPE : PLL into common hepatic artery in DNA dose of 10 to 30 mg every 3 to 4 weeks for 2 to 8 times (mean 4 times). Of 16 patients who underwent p53 gene therapy, 6 showed partial response, 4 minimal response and 3 stable disease. High level expression of WT p53 or p21 were found in tumor tissues of hepatovectin1 administered patients. After p53 gene therapy, 11 of 16 patients developed transient fever and chill, but none developed transient fever and chill, but none developed grade 4 toxicity or deterioration of liver function. Of 16 patients who underwent p53 gene therapy, 7 were alive on 1 year follow up and 9 died from metastatic cancer or liver cirrhosis-related complications. in contrast, none of control group survived for 1 year. These results suggest that cationic liposome-mediated p53 gene trasfer via hepatic artery may become a promising therapeutic modality for advanced liver cancer which carry mutation of p53 gene. Our studies strongly suggest that our cationic liposome-mediated p53 gene therapy may be a promising treatment modality for human cancers which carry mutation of p53 gene and failed by conventional therapies. Further stydies are necessary on the actual benefit of this experimental study and effective systemic delivery method of p53 gene.

Prospective Comparison of Intraductal Ultrasonography-Guided Transpapillary Biopsy and Conventional Biopsy on Fluoroscopy in Suspected Malignant Biliary Strictures

( Hyun Su Kim ),( Jong Ho Moon ),( Yun Nah Lee ),( Hyun Jong Choi ),( Hyun Woo Lee ),( Hee Kyung Kim ),( Tae Hoon Lee ),( Moon Han Choi ),( Sang-woo Cha ),( Young Deok Cho ),( Sang-heum Park ) 대한간학회 2018 Gut and Liver Vol.12 No.4

Background/Aims: In suspected malignant biliary strictures (MBSs), the diagnostic yield of endoscopic retrograde cholangiopancreatography (ERCP)-based tissue sampling is limited. Transpapillary forceps biopsy (TPB) under intraductal ultrasonography (IDUS) guidance is expected to improve the diagnostic accuracy in patients with indeterminate biliary strictures. We evaluated the usefulness of IDUS-guided TPB in patients with suspected MBS. Methods: Consecutive patients with suspected MBS were prospectively enrolled in the study. ERCP with IDUS was performed in all patients. Both conventional TPB and IDUS-guided TPB on fluoroscopy were performed in each patient. The primary outcome was the diagnostic accuracy of conventional TPB and IDUS-guided TPB. Results: The technical success rate of IDUS-guided TPB was 97.0% (65/67 patients). Of these 65 patients, the final diagnosis was malignancy in 61 patients (93.8%). On IDUS, the most common finding of IDUS was an intraductal infiltrating lesion in 29 patients (47.5%). The overall diagnostic accuracy was significantly higher using IDUS-guided TPB than that using conventional TPB (90.8% vs 76.9%, p=0.027). According to the subgroup analysis based on the tumor morphology, IDUS-guided TPB had a significantly higher cancer detection rate than conventional TPB for intraductal infiltrating lesions (89.6% vs 65.5%, p=0.028). Conclusions: IDUS-guided TPB appears to improve the accuracy of histological diagnosis in patients with MBS. (Gut Liver 2018;12:463-470)

Antioxidant and cytoprotective effects of morin against hydrogen peroxide-induced oxidative stress are associated with the induction of Nrf-2-mediated HO-1 expression in V79-4 Chinese hamster lung fibroblasts

Lee, Moon Hee,Cha, Hee-Jae,Choi, Eun Ok,Han, Min Ho,Kim, Sung Ok,Kim, Gi-Young,Hong, Su Hyun,Park, Cheol,Moon, Sung-Kwon,Jeong, Soon-Jeong,Jeong, Moon-Jin,Kim, Wun-Jae,Choi, Yung Hyun Spandidos Publications 2017 International journal of molecular medicine Vol.39 No.3

<P>Natural phytochemicals of plant origin, including flavonoids, have been found to be potent antioxidants providing beneficial effects against oxidative stress-related diseases. The present study was carried out to investigate the antioxidant properties of morin, a flavonoid originally isolated from the flowering plants of the Moraceae family. Superoxide dismutase (SOD)-like activity and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(center dot+)) radical scavenging activity were determined. We also investigated the cytoprotective effects of morin against hydrogen peroxide (H2O2)-induced DNA damage and apoptosis in V79-4 Chinese hamster lung fibroblasts. Our results demonstrated that morin had strong scavenging effects against ABTS' radicals with enhanced SOD activity, which varied in a dose-dependent manner. Morin was found to reduce H2O2-induced intracellular reactive oxygen species generation and nuclear DNA damage, and it recovered cell viability damaged by H2O2 via inhibition of mitochondrial dysfunction-mediated apoptosis. Notably, the treatment of V79-4 cells with morin markedly enhanced the expression of heme oxygenase-1 (HO-1) but not quinone oxidoreductase-1, which was associated with the increased expression and phosphorylation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and the downregulation of Kelch-like ECH-associated protein 1 expression. Based on our findings, we conclude that morin effectively ameliorated oxidative stress-induced DNA damage through intrinsic free radical scavenging activity and activation of the Nrf2/HO-1 pathway.</P>

First-Pass Recanalization with EmboTrap II in Acute Ischemic Stroke (FREE-AIS): A Multicenter Prospective Study

Baek Jang-Hyun,Kim Byung Moon,Suh Sang Hyun,Jeon Hong-Jun,Ihm Eun Hyun,Park Hyungjong,Kim Chang-Hyun,Cha Sang-Hoon,Choi Chi-Hoon,Yi Kyung Sik,Kim Jun-Hwee,Suh Sangil,Kim Byungjun,Chang Yoonkyung,Kim S 대한영상의학회 2023 Korean Journal of Radiology Vol.24 No.2

Objective: We aimed to evaluate the efficacy of EmboTrap II in terms of first-pass recanalization and to determine whether it could yield favorable outcomes. Materials and Methods: In this multicenter, prospective study, we consecutively enrolled patients who underwent mechanical thrombectomy using EmboTrap II as a front-line device. The primary outcome was the first pass effect (FPE) rate defined by modified Thrombolysis In Cerebral Infarction (mTICI) grade 2c or 3 by the first pass of EmboTrap II. In addition, modified FPE (mFPE; mTICI grade 2b–3 by the first pass of EmboTrap II), successful recanalization (final mTICI grade 2b–3), and clinical outcomes were assessed. We also analyzed the effect of FPE on a modified Rankin Scale (mRS) score of 0–2 at 3 months. Results: Two hundred-ten patients (mean age ± standard deviation, 73.3 ± 11.4 years; male, 55.7%) were included. Ninetynine patients (47.1%) had FPE, and mFPE was achieved in 150 (71.4%) patients. Successful recanalization was achieved in 191 (91.0%) patients. Among them, 164 (85.9%) patients underwent successful recanalization by exclusively using EmboTrap II. The time from groin puncture to FPE was 25.0 minutes (interquartile range, 17.0–35.0 minutes). Procedure-related complications were observed in seven (3.3%) patients. Symptomatic intracranial hemorrhage developed in 14 (6.7%) patients. One hundred twenty-three (58.9% of 209 completely followed) patients had an mRS score of 0–2. Sixteen (7.7% of 209) patients died during the follow-up period. Patients who had successful recanalization with FPE were four times more likely to have an mRS score of 0–2 than those who had successful recanalization without FPE (adjusted odds ratio, 4.13; 95% confidence interval, 1.59–10.8; p = 0.004). Conclusion: Mechanical thrombectomy using the front-line EmboTrap II is effective and safe. In particular, FPE rates were high. Achieving FPE was important for an mRS score of 0–2, even in patients with successful recanalization.

인체암에서 cationic liposome을 이용한 p53과 p21/WAF1 종양억제유전자 치료에 대한 연구

문우철,임현묵,차성재,심형진,기영진,엄태한,곽병국,유남숙,이창준 중앙대학교 의과대학 의과학연구소 1997 中央醫大誌 Vol.22 No.3

In vitro Virulence of Cultured Supernatant in Porphyromonas gingivalis W50 under Hemin and Menadione Limited Culture Condition

Moon, Sang-Eun,Cha, Joung-Dan,Kim, Ki-Gyung,Lee, Hyun-Ok,Kim, Kang-Ju 원광대학교 생체재료·매식연구소 1997 원광생체재료·매식 Vol.6 No.1

In order to investigate the change of virulence in P. gingivalis W50, in vitro virulence was measured by the change of cell activity in mouse 3T3 cell. The cell activity of cultured supernatant of P. gingivalis W50 in the presence of hemin was lower than that in the obsence of hemin and menadione, but there was no change according to the presence of menadione. These results suggest that the virulence of cultured supernatant in P. gingivalis W50 might be increased by hemin.

Zap70 Functions to Maintain Stemness of Mouse Embryonic Stem Cells by Negatively Regulating Jak1/Stat3/c-Myc Signaling

Cha, Young,Moon, Bo-hyun,Lee, Mi-ok,Ahn, Hee-jin,Lee, Hye-jin,Lee, Kyung-ah,Fornace Jr., Albert J.,Kim, Kwang-soo,Cha, Hyuk-jin,Park, Kyung-soon Wiley (John WileySons) 2010 Stem Cells Vol.28 No.9