Hypoxia-Responsive MicroRNA-101 Promotes Angiogenesis <i>via</i> Heme Oxygenase-1/Vascular Endothelial Growth Factor Axis by Targeting Cullin 3

Kim, Ji-Hee,Lee, Kwang-Soon,Lee, Dong-Keon,Kim, Joohwan,Kwak, Su-Nam,Ha, Kwon-Soo,Choe, Jongseon,Won, Moo-Ho,Cho, Byung-Ryul,Jeoung, Dooil,Lee, Hansoo,Kwon, Young-Guen,Kim, Young-Myeong Mary Ann Liebert 2014 Antioxidants & redox signaling Vol.21 No.18

<P>Aims: Hypoxia induces expression of various genes and microRNAs (miRs) that regulate angiogenesis and vascular function. In this study, we investigated a new functional role of new hypoxia-responsive miR-101 in angiogenesis and its underlying mechanism for regulating heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) expression. Results: We found that hypoxia induced miR-101, which binds to the 3 ' untranslated region of cullin 3 (Cul3) and stabilizes nuclear factor erythroid-derived 2-related factor 2 (Nrf2) via inhibition of the proteasomal degradation pathway. miR-101 overexpression promoted Nrf2 nuclear accumulation, which was accompanied with increases in HO-1 induction, VEGF expression, and endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) production. The elevated NO-induced S-nitrosylation of Kelch-like ECH-associated protein 1 and subsequent induction of Nrf2-dependent HO-1 lead to further elevation of VEGF production via a positive feedback loop between the Nrf2/HO-1 and VEGF/eNOS axes. Moreover, miR-101 promoted angiogenic signals and angiogenesis both in vitro and in vivo, and these events were attenuated by inhibiting the biological activity of HO-1, VEGF, or eNOS. Moreover, these effects were also observed in aortic rings from HO-1(+/-) and eNOS(-/-) mice. Local overexpression of miR-101 improved therapeutic angiogenesis and perfusion recovery in the ischemic mouse hindlimb, whereas antagomiR-101 diminished regional blood flow. Innovation: Hypoxia-responsive miR-101 stimulates angiogenesis by activating the HO-1/VEGF/eNOS axis via Cul3 targeting. Thus, miR-101 is a novel angiomir. Conclusion: Our results provide new mechanistic insights into a functional role of miR-101 as a potential therapeutic target in angiogenesis and vascular remodeling. Antioxid. Redox Signal. 21, 2469-2482.</P>

Hepatoprotective and Antioxidative Activities of <i>Cornus officinalis</i> against Acetaminophen-Induced Hepatotoxicity in Mice

Lee, Nam-Hun,Seo, Chang-Seob,Lee, Ho-young,Jung, Da-Young,Lee, Jun-Kyung,Lee, Jin-Ah,Song, Kye Yong,Shin, Hyeun-kyoo,Lee, Mee-Young,Seo, Young Bae,Kim, Hokyoung,Ha, Hyekyung Hindawi Publishing Corporation 2012 Evidence-based Complementary and Alternative Medic Vol.2012 No.-

<P>The fruit of <I>Cornus officinalis </I>Sieb. et Zucc. is commonly prescribed in Asian countries as a tonic formula. In this study, the hepatoprotective effect of ethanolic extracts of the fruit of <I>C. officinalis</I> (ECO) was investigated in a mouse model of acetaminophen- (APAP-) induced liver injury. Pretreatment of mice with ECO (100, 250, and 500 mg/kg for 7 days) significantly prevented the APAP (200 mg/kg) induced hepatic damage as indicated by the serum marker enzymes (AST, ALT, and LDH). Parallel to these changes, ECO treatment also prevented APAP-induced oxidative stress in the mice liver by inhibiting lipid peroxidation (MDA) and restoring the levels of antioxidant enzymes (SOD, CAT, and HO-1) and glutathione. Liver injury and collagen accumulation were assessed using histological studies by hematoxylin and eosin staining. Our results indicate that ECO can prevent hepatic injuries associated with APAP-induced hepatotoxicity by preventing or alleviating oxidative stress.</P>

Validation of the oxford classification of iga nephropathy: A Single-Center Study in Korean Adults

( Ho Young Lee ),( Sul Hee Yi ),( Mi Seon Seo ),( Jin Nam Hyun ),( Jin Seok Jeon ),( Hyunjin Noh ),( Dong Cheol Han ),( Seung Duk Hwang ),( So Young Jin ),( Soon Hyo Kwon ) 대한내과학회 2012 The Korean Journal of Internal Medicine Vol.27 No.3

Background/Aims: The recently published Oxford classification of IgA nephropathy (IgAN) proposed a split system for histological grading, based on prognostic pathological features. This new classification system must be validated in a variety of cohorts. We investigated whether these pathological features were applicable to an adult Korean population. Methods: In total, 69 adult Korean patients with IgAN were analyzed using the Oxford classification system at Soonchunhyang University Hospital, Seoul, Korea. All cases were categorized according to Lee`s classification. Renal biopsies from all patients were scored by a pathologist who was blinded to the clinical data for pathological variables. Inclusion criteria were age greater than 18 years and at least 36 months of follow-up. We excluded cases with secondary IgAN, diabetic nephropathy combined other glomerulopathies, less than 36 months of follow-up, and those that progressed rapidly. Results: The median age of the patients was 34 years (range, 27 to 45). Mean arterial blood pressure was 97 ± 10 mmHg at the time of biopsy. The median follow-up period was 85 months (range, 60 to 114). Kaplan-Meier analysis showed significant prognostic predictions for M, E, and T lesions. A Cox proportional hazard regression analysis also revealed prognostic predictions for E and T lesions. Conclusions: Using the Oxford classification in IgAN, E, and T lesions predicted renal outcome in Korean adults after taking clinical variables into account.

만성두통 환자의 성격유형 A 행태, 스트레스, 우울 및 두통영향정도의 관계 연구

차남현,임사비나,정인태,김수영,안경애,김건식,이재동,이상훈,최도영,이윤호,이두익 EAST-WEST MEDICAL RESEARCH INSTITUTE KYUNG HEE UNI 2005 東西醫學硏究所 論文集 Vol.2005 No.-

To examine an estimate factor and grasp the relation of difference for Ype A Behavior Pattern(TABP), Perceived Stress Questionnaire. Depression and HIT-6 in the Chronic headache client. Method: Data collected by self-reported questionnaires from 38 client in S city who were selected by criteria of IHS, from the 19^(th) of October to 10^(th) of December, 2004. Result: 1) Differences between biographical data by TABP was significant by SaSang constitutions, by Stress was significantly influenced by age, and by Depression were significantly influenced health status and SaSang constitutions. 2) Correlations Coefficients among Study Variables were Stress and Depression(r=.494, p=.002) and Depression and HIT-6(r=.432, p=.010). 3) In regression analysis, HIT-6 were significantly influenced by Depression and Type A Behavior Pattern(TABP). These variables explained 38% and 34% respectively. Conclusion: The result suggest that chronic headache management with psychological aspect, as well as physical aspect should be a focus to enhance the quality of life.

만성두통환자에 대한 침치료가 심박변이도에 미치는 영향

정인태,이상훈,김수영,차남현,김건식,이두익,이재동,임사비나,이윤호,최도영 EAST-WEST MEDICAL RESEARCH INSTITUTE KYUNG HEE UNI 2005 東西醫學硏究所 論文集 Vol.2005 No.-

Objective : The purpose of this study was to assess the effect of acupuncture treatment for chronic headache patients using power spectrum analysis of the heart rate variability(HRV). Methods : 15 clinical experiment participants were gathered and through a questionnaire patients who experienced headache for more than 4 hours a day and more than 15 days per month were qualified as Chronic Headache patients. Treatment was applied 2 times a weeks for 8 weeks. The acupoints, GV20, HN23, ST8, HN46, TE17, GB20, LI20, LI11, LI14, ST36, and LR3 were stimulated for 20 minutes. The effects of acupuncture treatment were analyzed using power spectrum analysis of the HRV, HRV was recorded before and after acupuncture treatment. Results : HRV before and after treatment was compared after 8 weeks of acupuncture treatment. Increase in mean values of SDNN and RMSSD were observed but the increases were not statistically significants. Increase in mean values of TP, LF and HF were observed but, the increase was significant(p<0.05) only in TP. Conclusions : The results suggest that acupuncture treatment on chronic headache patients can increase the activity of autonomic nervous system. Further use of HRV for quantitative analysis of acupuncture treatment on autonomic nervous system related symptoms is suggested.

만성두통환자에 대한 동서협진의 임상적 연구

정인태,이상훈,김수영,차남현,김건식,이두익,이재동,임사비나,이윤호,최도영 EAST-WEST MEDICAL RESEARCH INSTITUTE KYUNG HEE UNI 2005 東西醫學硏究所 論文集 Vol.2005 No.-

Objective : Because the cause and etiology of chronic headache are not yet fully explained, the treatment of this symptom is not simple. In order to study the effectiveness East-West pain treatment on chronic headache, we evaluated its effect of pain alleviation and quality of life improvement on chronic headache patients who were treated with nerve block and acupuncture, and only acupuncture for eight weeks. Methods : 92 clinical experiment participants were gathered and through a questionnaire patients who experienced headache for more than 4 hours a day and more than 15 days per month were qualified as chronic headache patients. The qualified patients were classified into two groups, nerve block and acupuncture group(EW group, n=49) and acupuncture group(E group, n=43). Treatment was applied 2 times a weeks for 8 weeks. The acupoints, GV20, HN23, ST8, HN46, TE17, GB20, LI20, LI11, LI14, ST36, and LR3 were stimulated for 20 minutes. The effects of two groups were analyzed using VAS scores and BPI(Brief Pain Inventory). Results : The VAS and BPI after four weeks of treatment showed significant improvement among two but differences between the three groups was statistically insignificant. The VAS and BPI of the EW group after eight weeks of treatment showed statistically significant improvement compared to the other two groups. Conclusion : The pain treatment for chronic headache might be contributed to improvement of quality of life as well as alleviation of pain of chronic headache patients. It was suggested that the West pain treatment in combination with East pain treatment might be an useful modality to improve the pain and quality of life in chronic headache patients.

작업관련성 수근관증후근 감시체계

정우철,권호장,하미나,노상철,권범선,현정근,이성재,이종민,권정이,김준성,백남종,이호,이경우,이삼규 大韓産業醫學會 2004 대한직업환경의학회지 Vol.16 No.1

목적: 작업관련 근골격계질환은 중요한 직업관련성 질환 중의 하나이고 작업관련 수근관증후군은 이러한 작업관련 근골격계질환 중에서도 많은 부분을 차지한다. 이 연구는 작업관련 수근관증후군의 역학적 특성에 대해 알아보고자 수행되었다. 방법: 본 연구에서는 '수근관증후군 감시체계'를 통해 2000년 6월부터 2003년 2월까지 보고 된 672례의 수근관증후군 사례를 분석하였다. 직업력이 확인된 314명을 대상으로는 직업 및 작업내용에 따라 작업관련성 수근관증후군의 비율이 어떻게 달라지는지를 분석함으로써 수근관증후군 위험요인을 조사하였다. 결과: 직업력이 확인된 314명의 환자 중 작업 관련성이 의심되는 사람은 228명 (72.6%) 이었다. 직업별로는 '단순노무종사자', '농림어업숙련자', '서비스종사자' 등에서 작업관련 수근관증후군의 비율이 여성에서 유의하게 높게 나타났으나 연령, 비만도 지수, 과거병력 등에 따른 차이는 관찰되지 않았다. 주관적 증상 중에 '손을 많이 사용한 후 심해진다'와 '손을 털면 덜해진다'라는 항목을 작업관련성 수근관증후군 환자에서 더 많이 호소하였고 다른 증상은 별다른 차이를 보이지 않았다. 작업관련성 수근관증후군 환자가 비교적 많이 노출되는 작업은 '지나치게 손을 뻗쳐서 하는 일', '손을 불편한자세로 유지하는 일' 등이었다. 결론: 전체 수근관증후군 중 작업관련성이 있다는 비율이 매우 높은 것을 확인할 수 있었다. 수근관증후군 감시체계가 작업관련성 수근관증후군의 여러 특성을 밝히는데 매우 효과적인 것으로 나타났으나 현재까지는 중재 대상을 구체적으로 특정하기에는 한계가 있다. Objectives: Carpal tunnel syndrome (CTS) is one of the most important work related musculo-skeletal diseases in Korea. However, there are few epidemiologic studies on the work-related CTS (WR-CTS). This study aimed to investigate the epidemiologic characteristics of WR-CTS in Korea. Methods: Data obtained from the "CTS Surveillance System". Physician case-reports in the surveillance were used to document patterns of WR-CTS by age, gender, occupation, sign, symptom, working history. Results: Six hundred and seventy-two cases of WR-CTS were ascertained of which 3 14 with complete information on occupational history were analyzed. It has been estimated that as many as 72% of' all CTS cases are work-related. The highest proportion of WR-CTS was observed in 'elementary occupation workers', followed by 'skilled agricultural, forestry and fishery worker'. The distributions of WR-CTS cases were similar with respect to age, obesity, and past medical history. The proportion of WR-CTS was higher in females. There was no significant difference in physical examination findings between WR-CTS and non WR-CTS cases. Repetitive work and the inappropriate hand posture seemed to be the risks for WR-CTS. Conclusion: WR-CTS is a significant public health problem. The CTS surveillance system is quite useful to elucidate the characteristics of WR-CTS, but it remains of limited use in targeting specific industries and occupations for intervention.

복어중독에 의한 가사 상태에서 소생한 1예

송승찬,신진호,강석우,박경남,최호순,박근태,문희식,기춘석,이성희,윤병철,노우균,조균석,이민호 大韓應急醫學會 1998 대한응급의학회지 Vol.9 No.3

Tetrodotoxin is a neurotoxin produced by about 90 species of puffer fish and causes paralysis of central nervous system and peripheral nerves by blocking the movement of all monovalent cation. Ingestion of tetrodotoxin produces clinical manifestations such as paresthesias(within 10-45 min), vomiting, lightheadedness, salivation, muscle twitching, dysphagia, difficulty in speaking, convulsion and death that expressed by cardiopulmonary arrest with loss of brain stem reflex sometimes. Tetrodotoxin prevents or delays ischemia induced neuronal death by way of following 3 mechanisms. Firstly, it reduces the energy demand of the brain tissues. Secondly, it delays or even prevents anoxic depolarization. Finally, it deminishes ischemia induced cell swelling and cerebral edema. We report a case of puffer fish poisoning which presented with cardiopulmonary arrest and loss of brain stem reflex, but completely recovered by aggressive cardiopulmonary resuscitation.

심근 허혈-재관류 백서 모델에서 mitogen-activated protein kinase 활성화에 대한 α-lipoic acid의 효과

김연경,박은미,최준호,윤경호,유남진,이은미,김남호,정진원,김민선,박병림,오석규 圓光大學校 醫科學硏究所 2006 圓光醫科學 Vol.21 No.1

Effects of 17β-estradiol on colorectal cancer development after azoxymethane/dextran sulfate sodium treatment of ovariectomized mice

Song, Chin-Hee,Kim, Nayoung,Lee, Sun Min,Nam, Ryoung Hee,Choi, Soo In,Kang, So Ra,Shin, Eun,Lee, Dong Ho,Lee, Ha-Na,Surh, Young-Joon Elsevier 2019 Biochemical pharmacology Vol.164 No.-

<P><B>Abstract</B></P> <P>Estrogen is known to have a protective effect in colorectal cancer (CRC) development. Previously, we reported the anti-inflammatory and antitumorigenic effects of 17β-estradiol (E2) in azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated male mice. The aim of this study was to investigate whether ovariectomy in a female AOM/DSS mouse model increases colorectal tumorigenesis and whether tumorigenesis is reduced by estrogen supplementation after ovariectomy. Clinical symptoms and histological severity of colitis and the levels of inflammatory mediators were evaluated in the colon of AOM/DSS-treated ovariectomized (OVX) mice. The levels of E2, myeloperoxidase (MPO), and NF-κB-dependent cytokines (interleukin (IL)-1β and IL-6) were measured by ELISA. Furthermore, quantitative real-time (qRT) PCR and Western blot analysis were performed. Ovariectomy did not aggravate AOM/DSS-induced colitis at 2 weeks. At weeks 10 and 16, ovariectomy significantly increased tumor number and incidence rate in only the proximal colon after AOM/DSS treatment (F_AOM/DSS vs OVX_AOM/DSS), and these increases were significantly reduced by E2 supplementation (OVX_AOM/DSS vs OVX_AOM/DSS/E2). However, ovariectomy did not affect CRC development in the distal colon (F_AOM/DSS vs OVX_AOM/DSS). At week 2, E2 administration to AOM/DSS-treated OVX mice attenuated the histological severity of colitis by decreasing the protein and/or mRNA levels of estrogen receptor alpha (ERα) and NF-κB-related mediators (i.e., COX-2, TNF-α, and IL-6) and by enhancing estrogen receptor beta (ERβ) and nuclear Nrf2 protein expression and the mRNA expression of related antioxidant enzyme genes (i.e., HO-1, GCLC, GCLM, and NQO1). Endogenous estrogen in females protects against the development of proximal colon cancer, and exogenous E2 replacement in OVX female mice showed protective effects against AOM/DSS-induced colitis and carcinogenesis. The mechanism could involve modulating ERs-, NF-κB- and Nrf2-mediated pathways.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>