Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation

( Sun-uk Bak ),( Suji Kim ),( Hae-jun Hwang ),( Jung-a Yun ),( Wan-sung Kim ),( Moo-ho Won ),( Ji-yoon Kim ),( Kwon-soo Ha ),( Young-guen Kwon ),( Young-myeong Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2017 BMB Reports Vol.50 No.2

Heme oxygenase (HO-1) catalyzes heme to carbon monoxide (CO), biliverdin/bilirubin, and iron and is known to prevent the pathogenesis of several human diseases. We assessed the beneficial effect of heme degradation products on osteoclastogenesis induced by receptor activator of NF-κB ligand (RANKL). Treatment of RAW264.7 cells with CORM-2 (a CO donor) and bilirubin, but not with iron, decreased RANKLinduced osteoclastogenesis, with CORM-2 having a more potent anti-osteogenic effect. CORM-2 also inhibited RANKLinduced osteoclastogenesis and osteoclastic resorption activity in marrow-derived macrophages. Treatment with hemin, a HO-1 inducer, strongly inhibited RANKL-induced osteoclastogenesis in wild-type macrophages, but was ineffective in HO-1^+/-cells. CORM-2 reduced RANKL-induced NFATc1 expression by inhibiting IKK-dependent NF-κB activation and reactive oxygen species production. These results suggest that CO potently inhibits RANKL-induced osteoclastogenesis by inhibiting redox-sensitive NF-κB-mediated NFATc1 expression. Our findings indicate that HO-1/CO can act as an antiresorption agent and reduce bone loss by blocking osteoclast differentiation. [BMB Reports 2017; 50(2): 103-108]

Anti-Proliferative Effect of an Aqueous Extract of <i>Prunella vulgaris</i> in Vascular Smooth Muscle Cells

Hwang, Sun Mi,Lee, Yun Jung,Lee, Yong Pyo,Yoon, Jung Joo,Lee, So Min,Cha, Jeong Dan,Choi, Kyung Min,Kang, Dae Gill,Lee, Ho Sub Hindawi Publishing Corporation 2013 Evidence-based Complementary and Alternative Medic Vol.2013 No.-

<P>The abnormal proliferation of vascular smooth muscle cells (VSMCs) in arterial walls is an important pathogenic factor of vascular disorders such as diabetic atherosclerosis. We have reported the anti-inflammatory effect of an aqueous extract from <I>Prunella vulgaris</I> (APV) in vascular endothelial cell. In the present study, APV exhibited inhibitory effects on high glucose-stimulated VSMC proliferation, migration, and invasion activities, inducing G<SUB>1</SUB> cell cycle arrest with downregulation of cyclins and CDKs and upregulation of the CKIs, p21<SUP>waf1/cip1</SUP> and p27<SUP>kip1</SUP>. Furthermore, APV dose dependently suppressed the high glucose-induced matrix metalloproteinase activity. High glucose-induced phosphorylation of ERK, p38 MAPK, was decreased by the pretreatment of APV. NF-<I><I>κ</I></I>B activation by high glucose was attenuated by APV, as an antioxidant. APV attenuated the high glucose-induced decrease of nuclear factor E2-related factor-2 (Nrf2) translocation and heme oxygenase-1 (HO-1) expression. Intracellular cGMP level was also increased by APV treatment. These results demonstrate that APV may inhibit VSMC proliferation via downregulating ROS/NF-<I><I>κ</I></I>B /ERK/p38 MAPK pathways. In addition, APV has a beneficial effect by the interaction of Nrf2-mediated NO/cGMP with HO-1, suggesting that <I>Prunella vulgaris</I> may be useful in preventing diabetic atherosclerosis.</P>

<i>Prunella vulgaris</i> Suppresses HG-Induced Vascular Inflammation via Nrf2/HO-1/eNOS Activation

Hwang, Sun Mi,Lee, Yun Jung,Yoon, Jung Joo,Lee, So Min,Kim, Jin Sook,Kang, Dae Gill,Lee, Ho Sub Molecular Diversity Preservation International (MD 2012 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.13 No.1

<P>Vascular inflammation is an important factor which can promote diabetic complications. In this study, the inhibitory effects of aqueous extract from <I>Prunella vulgaris</I> (APV) on high glucose (HG)-induced expression of cell adhesion molecules in human umbilical vein endothelial cells (HUVEC) are reported. APV decreased HG-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. APV also dose-dependently inhibited HG-induced adhesion of HL-60 monocytic cells. APV suppressed p65 NF-κB activation in HG-treated cells. APV significantly inhibited the formation of intracellular reactive oxygen species (ROS). HG-stimulated HUVEC secreted gelatinases, however, APV inhibited it. APV induced Akt phosphorylation as well as activation of heme oxygenase-1 (HO-1), eNOS, and nuclear factor E2-related factor 2 (Nrf2), which may protect vascular inflammation caused by HG. In conclusion, APV exerts anti-inflammatory effect via inhibition of ROS/NF-κB pathway by inducing HO-1 and eNOS expression mediated by Nrf2, thereby suggesting that <I>Prunella vulgaris</I> may be a possible therapeutic approach to the inhibition of diabetic vascular diseases.</P>

말초혈액 내 백혈구수와 대사증후군과의 연관성

황상태,김범수,황상준,서정열,김병진,이원영,성기철,강진호,김선우,이만호,박정로 대한순환기학회 2004 Korean Circulation Journal Vol.34 No.3

Sulforaphane protects against acetaminophen-induced hepatotoxicity

Noh, Jung-Ran,Kim, Yong-Hoon,Hwang, Jung Hwan,Choi, Dong-Hee,Kim, Kyoung-Shim,Oh, Won-Keun,Lee, Chul-Ho Elsevier 2015 Food and chemical toxicology Vol.80 No.-

<P><B>Abstract</B></P> <P>Oxidative stress is closely associated with acetaminophen (APAP)-induced toxicity. Heme oxygenase-1 (HO-1), an antioxidant defense enzyme, has been shown to protect against oxidant-induced tissue injury. This study investigated whether sulforaphane (SFN), as a HO-1 inducer, plays a protective role against APAP hepatotoxicity <I>in vitro</I> and <I>in vivo</I>. Pretreatment of primary hepatocyte with SFN induced nuclear factor E2-factor related factor (Nrf2) target gene expression, especially HO-1 mRNA and protein expression, and suppressed APAP-induced glutathione (GSH) depletion and lipid peroxidation, which eventually leads to hepatocyte cell death. A comparable effect was observed in mice treated with APAP. Mice were treated with 300 mg/kg APAP 30 min after SFN (5 mg/kg) administration and were then sacrificed after 6 h. APAP alone caused severe liver injuries as characterized by increased plasma AST and ALT levels, GSH depletion, apoptosis, and 4-hydroxynonenal (4-HNE) formations. This APAP-induced liver damage was significantly attenuated by pretreatment with SFN. Furthermore, while hepatic reactive oxygen species (ROS) levels were increased by APAP exposure, pretreatment with SFN completely blocked ROS formation. These results suggest that SFN plays a protective role against APAP-mediated hepatotoxicity through antioxidant effects mediated by HO-1 induction. SFN has preventive action in oxidative stress-mediated liver injury.</P> <P><B>Highlights</B></P> <P> <UL> <LI> SFN pretreatment increases the cell viability against APAP-induced toxicity. </LI> <LI> SFN pretreatment protects depletion of cellular GSH after APAP treatment. </LI> <LI> SFN pretreatment enhances Nrf2 target gene expression, especially HO-1 after APAP treatment. </LI> <LI> SFN has protective effect against APAP overdose-induced liver injury <I>in vivo</I> model as well. </LI> </UL> </P>

원위 대퇴골의 고립성 골연골종에서 발생한 속발성 연골 육종 1례 보고

정필현,황장수,강석,김용민,오형호,채동주,김종필 동국대학교 경주대학 1996 東國論集 Vol.15 No.-

연골육종은 비교적 서서히 자라며 늦게 전이하는 악성 연골 종양으로 알려져 있다. 골 연골종에서 발생한 속발성 연골육종은 발생빈도는 드물며 타부위로의 전이가 적고 악성도가 낮은 경우가 많아 적합한 수술적 치료로서 좋은 예후를 보이는 것으로 보고되고 있다. 본 동국대학교 정형외과학 교실에서는 우측 대퇴골 원위부 골간단부에 생긴 고립성 골 연골종에서 이차적으로 발생한 연골육종을 치험한 바 문헌고찰과 함께 보고하는 바이다. A case of Secondary Chondrosarcoma Arising from Solitary Osteochondroma of the Distal Femur Department of Orthopaedic Surgery, College of Medicine, DongGuk University Phil Hyun Chung M.D., Jung Su Hwang M.D., Suk Kang M.D., Yang Mln Kim M.D., Hyung Ho Oh M.D., Dong Ju Chae M.D., Jong Pil Kim M.D. Chondrpsarcoma is a malignant cartilage-forming tumor that grows slowly and metastasis of this tumor occurs in late stage. Secondary chondrosarcomas arising from a solitary osteocartilaginous exostosis are rare and those have a better prognosis than other chondrosarcomas, and they rarely metastasize. We present our experience with a case of secondary chondrpsarcoma arising in solitary osteochondroma of distal metaphysis of right femur with clinical details.

Flattening class hierarchy for reorganization of object-oriented software

황석형,양해술,박정호 한국정보처리학회 2001 정보처리논문지 Vol.8-d No.6

최근의 객체지향 소프트웨어개발에서는 설계 및 유지보수와 관련된 많은 문제점들을 해결하기 위하여 클래스를 재설계하거나 클래스계층구조를 재구성하는 등 객체지향 소프트웨어에 대한 일련의 재이용 및 재구성기법이 사용되고 있다. 본 논문에서는 클래스계층구조의 재구성에 관한 정형적인 이론을 제공함으로써 클래스계층구조의 재구성에 e관하여 보다 수월하게 이해하고 적용할 수 잇도록 하였다. 구체적으로 본 논문에서는 객체지향 소프트웨어의 개발에 있어서 주요 골격이 되는 클래스계층구조를 평탄화시킨 형태로 정의한 평탄화된 클래스계층구조를 소개하고, 임의의 클래스계층구조를 평탄화된 형태로 변형시키기 위한 알고리즘을 제안하였다. 클래스계층구조를 평탄화함으로써 클래스계층구조상의 계승 및 집약관계가 각 인스턴스들에게 어떻게 사상되는가를 수월하게 파악할 수 있으며, 주어진 클래스계층구조로부터 생성가능한 객체를 그대로 유지보존할 수 있는 평탄화된 형태의 새로운 클래스계층구조를 구축할 수 있다. 평탄화된 클래스계층구조는 클래스계층구조를 재구성하여 객체지향 소프트웨어를 점증적으로 변화 발전시키거나 재이용함에 있어서 기초를 제공하는 등 중요한 역할을 수행한다. In the object-oriented software development, redesigning of classes and reorganizing of class hierarchy structures should be necessary to reduce many of the headaches of object-oriented software design and maintenance. To support this task, in this paper, we propose a theoretical foundation for class hierarchy reorganizations that is relatively complete, correct, formal and easy to understand and use. We introduce the flattened class hierarchy that characterizes the clan, hierarchy structures in object-oriented software evolution. And we also present an algorithm which transforms a given class hierarchy into the normalized form. The flattened class hierarchy helps us map the inheritance and aggregation paths in a class hierarchy to paths in an object hierarchy that is an instance of the class hierarchy. By applying the algorithm into a given class hierarchy, we can make a new, object-preserved, and flattened class hierarchy that is the cornerstone for reorganization of class hierarchy structure and plays an important role as a bridge on the incremental evolutionary changes and reuse of object-oriented software to reorganize class hierarchies.

장기투석을 받은 만성 신부전 환자에서 발생한 종양에 관한 고찰

황정화,이혜경,홍현숙,박재성,김대호,권귀향,최득린,황승덕,이희발 순천향의학연구소 1996 Journal of Soonchunhyang Medical Science Vol.2 No.2

The authors tried to evaluate tumor occurrence in long-term dialysis patients with chronic renal failure. Among 359 patients, 20 patients (about 5.6%) were diagnosed with malignancy during long-term dialysis from the period of 1983 to 1995 at our nephrology department. The ultrasonographic and computed tomographic findings including the clinical features of 20 patients that were retrospectively reviewed. The mean age of the patients was 53 (37-75)years old and the ratio of male to female was 9:1. Among the 20 cases, 7 cases of hepatoma (35%) were developed. Among them, urinary tract tumors such as renal and bladder cancer were developed in 4 (20%) and 2 (10%) of the cases. Other malignant tumors were lymphoma, stomach cancer, uterine cervical cancer, cholangiocarcinoma, lung cancer, meningioma, and acoustic neuroma one case of each (each of 5.3%). The most common tumor in patients with chronic renal failure, who were receiving long-term dialysis, was hepatoma and the second most common tumor was cancer of the urinary tract such as kidney and bladder.

2차원적 불순물 재 분포에 관한 공정 Simulator 개발

황호정,박화식 중앙대학교 기술과학연구소 1989 기술과학연구소 논문집 Vol.19 No.-

This paper presents an investigation of numeric approaches to efficient solution of diffusion equation describing the two-dimensional impurity redistribution phenomena in semiconductor during thermal oxidation. The numerical method to solve the two-dimensional moving boundary problems ueses boundary element techniques which based on Green's function.

혈액투석에 의해 유발된 조증 1례

정철호,박영남,이황희,김정범 啓明大學校 醫科大學 1994 계명의대학술지 Vol.13 No.4

Psychiatric complications in patients undergoing hemodialysis include depression, acute psychotic reactions, delirium, and mania. Mania during hemodialysis is not as common as depression, as evidenced by a paucity of such case reports in the foreign literature and by there is no such a report in domestic literature. We experienced the case of 39-year-old man with chronic renal failure secondary to chronic glomerulonephritis who developed mania during hemodialysis for about 2 months. He has been treated with haloperidol, clonazepam, and supportive psychotherapy. With 3 months follow up, has been doing well and has returned to work.