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>

서울의 Penicillinase Producing Neisseria Gonorrhoeae 발생빈도(1996)

김재홍,황동규,전재홍,김윤석,김중환,김용준,이창균,임동진,김현수,조창근,김경문,박상훈,전우형,김희성,이호정,차명수,김갑형,김형석,김석우,황지환,박병순,권오상,이민수,송기훈,성소영,이인섭,부태성 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.2

Background : In recent years, gonorrhea has been panedemic and remains one of the most commom STDs in the world, especially in developing countries. Objective & Methods: For the detection of a more effective therapeutic regimen and assessing the prevalence of PPNG, we have been trying to study the patients who have visited the VD Clinic of Choong-Ku Public Health Center in Seoul since 1980 by means of the chromogenic cephalosporin method. Results: In 1996, 139 strains of N. gonorrhoeae were isolated, among which 53(39.0%) were PPNG. Conclusion: Our results suggests that after a peak of 74.3% in 1993, the prevalence of PPNG in Seoul is gradually declining.

Slide Session : OS-IFD-07 ; Infectious Disease : In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus

( Myung Jin Lee ),( Kye Hyung Kim ),( Jong Youn Yi ),( Su Jin Choi ),( Chung Jong Kim ),( Nak Hyun Kim ),( Kyoung Ho Song ),( Pyoeng Gyun Choi ),( Ji Hwan Bang ),( Wan Beom Park ),( Eu Suk Kim ),( San 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus Myung Jin LEE1, Kye-Hyung KIM1, Jongyoun YI2, SuJin CHOI1, Chung-Jong KIM1, Nak- Hyun KIM1, Kyoung-Ho SONG1, Pyoeng Gyun CHOI1, Ji-Hwan BANG1, Wan Beom PARK1, Eu Suk KIM1, Sang-Won PARK1, Hong Bin KIM1, Nam Joong KIM1, Myoung- Don OH1 Seoul National University College of Medicine, Korea1, Pusan National University School of Medicine, Korea2 Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV). No effective antiviral therapy is proven yet, but clinical use of ribavirin (RBV) has been tried. We investigated the antiviral effect of RBV against SFTSV in vitro. Methods: To test for cytotoxicity of RBV, Vero cells were treated with different concentrations of RBV (3.90 to 500 μg/mL, two-fold dilution) and analyzed by cell viability MTS assay 48h post-infection. To determine antiviral activity of RBV against SFTSV, Vero cells were infected with SFTSV strain Gangwon/Korea/2012 at 100 TCID50 (50% tissue culture infective dose) per well in a 96-well plate, and RBV was added at the concentrations showing no or minimal cytotoxicity. Viral RNAs were extracted from the culture supernatants and quantifi ed using one-step real-time reverse transcription- PCR to amplify the partial large segment of SFTSV. Statistical analysis was done by one-way ANOVA with Tukey`s post hoc test. Results: Cytotoxicity due to RBV was not observed at RBV concentration =31.3 μg/ mL. Viral RNAs at 24h post-RBV treatment were reduced with increasing RBV concentrations (1-32 μg/mL), compared with those of mock-treated cells (P <0.01, Figure). Half maximal inhibitory concentration (IC50) of RBV was 3.69 μg/mL at 24h post-RBV treatment. Conclusions: Our study shows that RBV has antiviral effect against SFTSV in a dose-dependent manner. Further studies are required to evaluate the effi cacy of RBV in SFTS.

혈액암환자에서 조혈모세포 이식 후 따르는 헤르페스 바이러스 감영 양상

이호섭,탁희상,신성훈,김양수,남성진,김혜수,박진희,정수현,김성빈,김예나 고신대학교 의과대학 2010 고신대학교 의과대학 학술지 Vol.25 No.1

배경 : 헤르페스바이러스과에는 단순포진 바이러스(HERPES SIMPLEX VIRUS, HSV), 수두대상포진 바이러스 (VARICELLA-ZOSTER VIRUS, VZV), 엡스타인-바 바이러스 (EPSTEIN-BARR VIRUS, EBV), 그리고 거대세포 바이러스 (CYTOMEGALOVIRUS, CMV) 등이 있다. 헤르페스바이러스 감염은 혈액암환자에서 조혈모세포 이식 환자에서 전파 (dissemination), 이차감염, 세균 중복 감염의 심각한 합병증을 일으킬 수 있다. 하지만 항암약물치료를 받는 림파종 환자에서 항 바이러스 약제의 사용 용량과 기간에 대한 concensus는 없다. 헤르페스바이러스 감염에 대한 발생율과 위험인자를 후향성으로 분석하였다. 방법 : 고신대학교 복음 병원에서 1995년 6월부터 2009 년 2월 사이에 새롭게 진단되어 조혈모세포 이식을 받은 전체 58명의 환자들이 후향적으로 현 연구에 등록했다. 헤르페스 바이러스 감염은 임상적 진단, 혈청학적 검사 또는 병리학적 진단에 기초하여 확진한다. 환자들의 특성은 다음과 같다: 평균 연령은 44세 (범위 19-62세)였고 남녀비는 30:28이었다. 등록된 질환은 백혈병 (n=9, 15.5%), 림프종 (n=30, 51.7%), 다발성 골수종 (n=12, 20.7%), 재생불량성 빈혈 (n=6, 10.3%) 그리고 골수이형성증후군 (n=1, 1.7%)이 포함되었다. 결과는 chi-squre test나 independent samples T test를 사용하여 분석되었다. Multivariate analysises에 대해 logistic regression test를 사용하였다. 결과 : 15명의 환자들 (25.9%)에서 조혈모세포 이식후 헤르페스 바이러스 감염이 발생하였다. 조혈모세포 이식 5년간 누적 발생율은 53.9%였다. Univariate analyses에서 헤르페스 바이러스 감염에 대한 유의한 위험 인자는 없었다. 하지만 조혈모세포 이식후 생존 기간(40.18 ± 30.14 months vs 20.06 ± 26.67 months, p=0.018)은 헤르페스 바이러스 감염의 낮은 발병율과 유의한 관련성이 있었다. 이식 편대 숙주질환 (GVHD)의 존재 (37.5% in developed GVHD vs 0% in no GVHD, p=0.200), 동종조혈 모세포 이식에서 면역억제요법의 기간 (15.98 ± 14.02 months vs 6.78 ± 3.67 months, p = 0.374)은 헤르페스 바이러스 감염에 대한 위험인자가 아니었다. 결론 : 조혈모세포 이식 후 생존 기간은 어사이클로비어 예방을 받은 혈액암 환자에서 헤르페스 바이러스 감염의 낮은 발병율과 연관성이 있는 것으로 보인다. 저용량의 어사이클로비어 예방은 헤르페스 바이러스 감염의 고위험군인 조혈모세포 이식을 받은 혈액암 환자에 필요하리라 생각된다. Background : Herpesviridae family includes herpes simplex virus, varicella zoster virus, Epstein-Barr virus, and cytomegalovirus, etc. Herpesviridae viral infection (HVI) can lead to serious complications including dissemination, secondary infection, bacterial superinfection in patients with hematologic malignancy following hematopoietic stem cell transplantation (HSCT). But there was no consensus on the dose and duration of antiviral agents prophylaxis in patients undergoing chemotherapy. We retrospectively analyzed the incidence and the risk factors for HVI. Method : A total of 58 patients who newly diagnosed and received HSCT with prophylaxis of acyclovir at the Kosin University Gospel Hospital, Busan, Korea between June 1995 and February 2009 were enrolled retrospectively in the current study. HVI was confirmed based on clinical diagnosis, serologic test or pathologic diagnosis. The characteristics of the patients were as follows: the median age was 44 years (range 19-62 years) with a female-to-male ratio of 30:28. The enrolled diseases included leukemia (n=9, 15.5%), lymphoma (n=30, 51.7%), multiple myeloma (n=12, 20.7%), aplastic anemia (n=6, 10.3%) and myelodysplastic syndrome (n=1, 1.7%). The results were analyzed using a chi-square test and independent samples T test. For the multivariate analysis, we used logistic regression test. Results : Fifteen patients (25.9%) developed HVI after HSCT. The cumulative incidence of HVI was 53.8% at 5 years after HSCT. In univariate analysis, there was no significant risk factor for HVI. The presence of graft-versus-host disease (GVHD) (37.5% in developed GVHD vs. 0% in no GVHD, p=0.200), duration of immunosuppressive therapy (IST) in allo-SCT (15.98 ± 14.02 months vs. 6.78 ± 3.67 months, p = 0.374) were not risk factors for HVI. Conclusion : The incidence of HVI was similar to that in historical other studies. There was no risk factor associated with development of HVI. Most of the HVI occurred within the first 24 months after transplantation. So long term use of antiviral prophylaxis may be needed to prevention of HVI after HSCT.

신경세포의 Outgrowth 향상을 위한 마이크로 파이버 지지체와 전단응력의 영향

김인애,박수아,김영직,김수향,신호준,이용재,신지원,신정욱 한국공작기계학회 2005 한국공작기계학회 춘계학술대회논문집 Vol.2005 No.-

We introduced mechanical stimuli and micro patterned substrate with micro fibers to investigate the effects of those on neurite outgrowth along with nerve growth factor (NGF) in vitro. Micro fiber substrates were fabricated using an electros pinning process. And PC-12 cells cultured on substrates were simulated with newer growth factor and laminar flow shear stress in a fluid flow system. The results suggest that micro fiber substrates and fluid-induced shear stress are promising for simulating neuronal regeneration in a desired direction.

하악골 절제술후 재이식된 돌결자가골 재이식 : 치험 3례

김 식,김수관,김운규,김수민,류종희,이준길,조경안,김수흥,정태영,여환호 대한악안면성형재건외과학회 2001 Maxillofacial Plastic Reconstructive Surgery Vol.23 No.2

We described three cases of immediate reimplantation of a frozen-thawed autogenous mandible composed of a mixture of iliac bone, marrow, and particulate hydroxyapatite in tumors of the mandible. Acceptable outcomes were obtained in three patients who underwent immediate autogenous mandibular graft reconstruction. The conditions leading to successful outcome of the procedure are also discussed. Reimplantation of frozen autogenous lesioned mandible was performed in three patients with mandibular tumors. Two reimplanted grafts survived without complications following surgery. One case had postoperative infection that resolved with appropriate antibiotic treatment. There were no recurrences of the primary lesions. Satisfactory facial contour after surgery was achieved. These results are most promising, and we believe that, with further refinement, this technique will offer a new and acceptable modality for facial reconstruction in patients with cancer.

신장이식 환자에서 HCMV 항원혈증 검사의 임상적 유용성

김탁,성흥섭,박관태,김송철,김성한,최상호,김양수,우준희,박수길,한덕종,이상오 대한감염학회 2009 감염과 화학요법 Vol.41 No.2

Background : This study was performed to determine the cut-off value and the predictability of symptomatic human cytomegalovirus (HCMV) infection according to the peak value of HCMV antigenemia assay in kidney transplant recipients. Materials and Methods : We reviewed the results of HCMV antigenemia assay (Chemicon, CA, USA) in patients who received kidney transplantation at our institution from May 2003 through May 2008, and investigated the existence and the type of HCMV infection by the medical record review. Patients who underwent the test only once during the episode or those who received ganciclovir for more than 48hrs before the test were excluded. The receiver-operator characteristic curve was drawn and the point showing maximum likelihood ratio (LR) was chosen as the cut-off value of symptomatic HCMV infection. Results : A total of 689 episodes were screened and 134 episodes were enrolled. Thirty-three (24.6%) episodes were symptomatic HCMV infection, 23 (17.2%) episodes were associated with HCMV syndrome, and 10 (7.5%) episodes were tissue-invasive diseases. The maximum LR was 7.5 (95% confidence interval, 4.014.2) and the cut-off value was 29.5 cells/200,000 WBC. The sensitivity, specificity, Positive predictive value, and negative predictive value were 66.7%, 91.1%, 71.0%, and 89.3%, respectively. Conclusions : The cut-off value of symptomatic HCMV infection by the peak value of HCMV antigenemia assay in our study was similar with previous results, although the sensitivity was relatively low.

Bucillamine prevents cisplatin-induced ototoxicity through induction of glutathione and antioxidant genes

Kim, Se-Jin,Ho Hur, Joon,Park, Channy,Kim, Hyung-Jin,Oh, Gi-Su,Lee, Joon No,Yoo, Su-Jin,Choe, Seong-Kyu,So, Hong-Seob,Lim, David J,Moon, Sung K,Park, Raekil Nature Publishing Group 2015 Experimental and molecular medicine Vol.47 No.2

<P>Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of γ-glutamylcysteine synthetase (γ-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine <I>in vivo</I>. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH.</P>

정신분열병 환자의 가족부담 척도 개발에 대한 예비연구

김철권,조진석,서지민,김용관,김호찬,김현수,김상수,제영묘 大韓神經精神醫學會 1999 신경정신의학 Vol.38 No.3

연구목적 : 정신분열병 환자의 가족이 느끼는 부담을 측정하기 위한 가족부담 척도를 개발하기 위함이다. 방 법 : 200명의 정신분열병 환자 가족과의 비구조적 면담과 외국 부담척도 고찰을 통하여 94문항을 수집하였고 그 다음에 전문가들과 가족들이 문항 및 영역을 분류하고 통합하여 최종적으로 36문항을 선정하였다. 그리고 정신분열병 환자의 가족 135명, 불안장애 환자의 가족 22명, 기분부전장애 및 신체화 장애 환자의 가족 26명, 치매 환자의 가족 49명을 대상으로 신뢰도와 타당도를 검증하였다. 결 과 : 자료분석 결과 검사-재검사 신뢰도, 내적 일치도, 감별타당도 모두 높게 나타났으며, 요인분석을 통해 다섯 가지 구성요인이 추출되었다. 결 론 : 본 가족부담 척도는 정신분열병을 포함한 만성 정신질환을 앓고 있는 환자의 호전과 가족의 부담을 덜어주기 위한 다양한 프로그램의 효과를 검증하는데 유용하게 사용되어질 수 있을 것이다. Objectives : This preliminary study was carried out to develop the Family Burden Scale(FBS) of the schizophrenics. Methods : Ninety-four items were collected by interviewing in a free unstructured format with one relative of each 200 schizophrenic patients and reviewing foreign FBS's. Several professionals and relatives were asked to group and integrate them into several categories. Finally 36 burden items were chosen to constitute a FBS. The FBS was administered to the relatives of 135 schizophrenic, 22 anxiety disorder, 26 dysthymic disorder and somatization disorder, and 49 dementia patients for examining the reliability and validity. Results : The FBS showed high test-retest reliability, internal consistency, and discriminant validity. The results of the factor analysis revealed five-factor solution. Conclusion : The FBS can be used to evaluate the effectiveness of various programs intended not only to reduce decompensation among schizophrenics, but also to alleviate family burden.

Anti-Inflammatory and Cytoprotective Effects of TMC-256C1 from Marine-Derived Fungus <i>Aspergillus</i> sp. SF-6354 via up-Regulation of Heme Oxygenase-1 in Murine Hippocampal and Microglial Cell Lines

Kim, Dong-Cheol,Cho, Kwang-Ho,Ko, Wonmin,Yoon, Chi-Su,Sohn, Jae Hak,Yim, Joung Han,Kim, Youn-Chul,Oh, Hyuncheol MDPI AG 2016 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.17 No.4

<P>In the course of searching for bioactive secondary metabolites from marine fungi, TMC-256C1 was isolated from an ethyl acetate extract of the marine-derived fungus <I>Aspergillus</I> sp. SF6354. TMC-256C1 displayed anti-neuroinflammatory effect in BV2 microglial cells induced by lipopolysaccharides (LPS) as well as neuroprotective effect against glutamate-stimulated neurotoxicity in mouse hippocampal HT22 cells. TMC-256C1 was shown to develop a cellular resistance to oxidative damage caused by glutamate-induced cytotoxicity and reactive oxygen species (ROS) generation in HT22 cells, and suppress the inflammation process in LPS-stimulated BV2 cells. Furthermore, the neuroprotective and anti-neuroinflammatory activities of TMC-256C1 were associated with upregulated expression of heme oxygenase (HO)-1 and nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in HT22 and BV2 cells. We also found that TMC-256C1 activated p38 mitogen-activated protein kinases (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways in HT22 and BV2 cells. These results demonstrated that TMC-256C1 activates HO-1 protein expression, probably by increasing nuclear Nrf2 levels via the activation of the p38 MAPK and PI3K/Akt pathways.</P>