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>

鹽生植物 나문재의 生育特性과 利用可能性

이봉호,문윤호,정병춘,김관수,류수노 한국국제농업개발학회 2002 韓國國際農業開發學會誌 Vol.14 No.2

기능성식품 원료, 채소, 식물성 소금 재료 및 제염식물 등으로 개발이 유망시되는 염생식물인 나문재의 육지부 재배 가능성을 조사하고, 내륙지방에서의 작물화 가능성을 검토코자 전남 서해안의 염전 부근에 자생하는 나문재의 종자와 식물체를 공시하여 내륙지방인 전남 무안군 소재의 『목포시험장』포장에서 시험하였던 바 그 결과를 요약하면 다음과 같다. 가. 나문재는 식물체를 이식하여도 생육이 양호할 뿐만 아니라 2년 묵은 종 자에서도 발아가 잘되었으며 발아소요 기간은 9일 정도 였고, 나문재의 생육은 소금기가 부족한 내륙에서도 비교적 양호하였으며, 병충해나 기타 재해도 거의 없어 내륙에서의 재배화 가능성이 높은 것으로 인정되었다. 나. 나문재의 생육에 미치는 소금물의 공급 효과를 검토하기 위해 1주일 간격으로 바닷물 농도의 소금물을 공급한 결과, 초장은 소금물을 공급한 것이 공급하지 않은 것 보다 양호하였으나 줄기의 굵기와 분지발생 수 는 소금물 공급효과가 크지 않았다. 다. 나문재의 생체중과 건물중은 종자파종의 경우 7월 10일 현재 소금물 처리구는 각각 주당 33.75g, 2.62g인데 비해 무처리구는 각각 23.52g, 1.84g으로서 소금물 처리구가 무겁고, 생체중에 대한 건물중의 비율은 대체로 7.14∼11.58% 범위로서 수분함량은 92.86∼88.42%정도 되는 다육식물 이었다. 라. 결론적으로 나문재는 소금기가 많은 곳에서 잘 생육할 뿐만 아니라 소금 기가 적은 곳에서도 생육이 비교적 양호하며, 식물전체에 짠맛을 가지고 있으므로 식물성 소금, 기능성 식품, 채소, 그리고 간척지나 음식물쓰레기의 염분제거 식물로서의 이용 가능성 등에 대한 보다 면밀한 검토가 필요하다고 보여진다. The plant of halophyte, Suaeda asparagoides MIQ, which is mainly inhabit on tidal flat was investigated on their growth characteristics and cultural traits on inland condition, in order to get some informations on it's possible use for functional food, vegetables, medicinal herb, and salt removing plant from tideland, or food-waste. The plant, Suaeda asparagoides M_IQ., is well grown on inland condition. But the salt applicated plants were better than those of the non-treated plants in its vegetable growth. The plant height is about 78.5cm in salt application, compared to the 64.5cm in non-treated plot. But the stem diameter and the number of branches are not better in salt application compared to the non-treated ones. However, the fresh weight and dry weight of the plant in salt-application are better than those of the non-treated ones, which means the total biomass is more productive by the salt application. As a conclusion, the plant Suaeda asparagoides M_IQ, seems to be an available plant and need to more discussion for possible use mentioned in the above sectors, from the results of inland cultivation of which well grown and characteristics.

Implication of necrosis-linked p53 aggregation in acquired apoptotic resistance to 5-FU in MCF-7 multicellular tumour spheroids

Lee, Su Yeon,Jeong, Eui-Kyong,Jeon, Hyun Min,Kim, Cho Hee,Kang, Ho Sung Spandidos Publications 2010 Oncology reports Vol.24 No.1

<P>Three-dimensional (3D) multicellular tumour spheroids (MTS) have been used as an in vitro model of solid tumours for drug resistance studies because they mimic the growth characteristics of in vivo tumours more closely than in vitro two-dimensional (2D) culture of cancer cell lines. As observed in solid tumours, MTS exhibits a proliferation gradient with outer regions consisting of proliferating cells that surround inner quiescent cells. The innermost cells in core regions undergo cell death mostly by necrosis to form necrotic core due to insufficient supply of oxygen and nutrient such as glucose with increasing size of spheroids. Tumour necrosis is thought to indicate a poor prognosis and to contribute to acquisition of chemoresistance in solid tumours; however, the mechanism underlying necrosis-mediated chemoresistance remains unclear. In this study, we examined the chemoresistance to 5-Fluorouracil (5-FU) using MCF-7 breast cancer MTS. 5-FU (400 microM) induced apoptosis in MCF-7 cell monolayer as determined by HO/PI staining, PARP cleavage, p53 induction, Bax induction, and Bcl-2 down-regulation. When MCF-7 breast tumour spheroids were cultured on agarose for 8 days, they reached approximately 700 microm in diameter, with a necrotic core. We found that 5-FU-induced apoptosis is markedly reduced in spheroids that were cultured for 9 days and had necrotic core, compared with MCF-7 monolayer cells and spheroids that were cultured for 6 days and had no necrotic core, indicating that the formation of necrotic core may be linked to acquisition of chemoresistance to 5-FU. We also found that a specific set of cellular proteins including p53 was aggregated into a RIPA-insoluble form during MTS culture. Furthermore, most of p53 induced by 5-FU was aggregated in MTS with necrotic core. Our results suggest that necrosis-linked p53 aggregation may contribute to acquired apoptotic resistance to 5-FU in MTS model system.</P>

권역단위 농촌지역개발사업의 주민역량 측정을 위한 설문도구개발

리신호 ( Shin Ho Rhee ),민흥기 ( Heung Gi Min ),윤성수 ( Sung Soo Yoon ),정남수 ( Nam Su Jung ),장우석 ( Woo Seok Chang ) 한국농촌계획학회 2014 농촌계획 Vol.20 No.4

The purpose of this study was to develop survey tools for diagnosis of capacity levels in business promotion of rural residents when performing a rural development project of a regional unit. The cases of previous studies were analyzed to select community capacity indicators related to a rural development project. Five indicators were derived : social capital, consciousness of participation, community spirit, and leadership. Based on the five indicators, measurement items of various capacities were selected and 54 survey items were selected through evaluation of experts twice. The pilot tests were conducted and targeted at Jeonnam song ho-jung village and Gyeongnam Haegeumgang village to identify derived survey items. In addition, descriptive statistic analysis and reliability analysis were conducted. As a result, survey items were corrected by reducing 10 items of the total 54 items. This results showed that using this tool could help us understand capacity levels of rural residents.

카드뮴 축적 변이주인 Pseudomonas maltophilia H - 8M의 특성

류병호(Beung-Ho Ryu),노명훈(Myung-Hoon Rho),정수자(Su-Ja Jung),배기철(Ki-ChuI Bae) 한국식품영양과학회 1992 한국식품영양과학회지 Vol.21 No.1

본 연구는 cadmium의 축적균주인 Pseudomonas maltophilia H-8을 MNNG로 처리하여 cadmium축적능이 가장 우수한 변이균주인 Pseudomonas maltophilia H-8M을 얻었고 그 특성을 조사하였다. 변이주 Pseudomonas maltophilia H-8M은 카드뮴농도 1,000ppm에서 36시간 배양했을 시 대조구에 비해 약 80%정도의 성장율을 나타내었다. 카드뮴 이외의 중금속의 첨가에 따른 생육상은 Pb^(2+), Zn^(2+), Hg^(2+), Cu^(2+), Cr^(2+), Co^(2+)등에는 별다른 성장 억제는 없었으나 Sn^(2+)에서는 생육억제가나타났다. 또한 50ppm의 카드뮴을 배지에 첨가 하였을 때 균체내 카드뮴 축적율은 52.92%로 가장 높게 나타났으며 축적부위는 세포벽에 80.3%의 축적율을 나타내었다. This study was carried out to investigate the characteristics of a mutant, Pseudomonas maltophilia Ho8M selected with the treatment of Pseudomonas maltophilia H-8 by N-methyl-N-nitro-N-nitrosoguanidine (MNNG). This mutant showed highest ability of cadmium accumulation. The growth rate of Pseudomonas maltophilia H-8M showed about 80% in 1000ppm Cd containing medium when compare with control for 36h at 30℃. Pseudomonas maltophilia H-8M not inhibited on the growth in addition of various heavy metal such as Hg^(2+), Zn^(2+), Pb^(2+), Cu^(2+), Cr^(2+) and Co^(2+), but inhibited in Sn^(2+) containing medium, respectively. Pseudomonas maltophilia H-8M was accumulated the highest cadmium level of 62.3% on whole cell in the medium containing 50 ppm and 80% of accumulated cadmium was distributed in the cell wall.

Hydrothermal synthesis and application of Ho³⁺-activated NaYbF₄ bifunctional upconverting nanoparticles for <i>in vitro</i> cell imaging and latent fingerprint detection

Du, Peng,Zhang, Peng,Kang, Seong Ho,Yu, Jae Su Elsevier 2017 Sensors and actuators. B Chemical Vol.252 No.-

<P><B>Abstract</B></P> <P>The Ho<SUP>3+</SUP>-activated NaYbF<SUB>4</SUB> upconverting nanoparticles (UCNPs) were synthesized <I>via</I> a facile hydrothermal method and characterized by X-ray diffraction pattern, transmission electron microscope image and upconversion (UC) emission spectrum. Upon the excitation of 980nm light, the as-prepared UCNPs exhibited bright green and red UC emissions corresponding to the (<SUP>5</SUP>F<SUB>4</SUB>,<SUP>5</SUP>S<SUB>2</SUB>) → <SUP>5</SUP>I<SUB>8</SUB> and <SUP>5</SUP>F<SUB>5</SUB> → <SUP>5</SUP>I<SUB>8</SUB> transitions of Ho<SUP>3+</SUP> ions, respectively. The cell toxicity test result revealed that the synthesized UCNPs possessed remarkable low cytotoxicity. With the introduction of the resultant UCNPs into the HeLa cells, intense green and red UC emissions were observed, indicating that the HeLa cells can be labeled by the obtained UCNPs and they had potential application in live cell imaging. Additionally, the practicality of the resultant UCNPs for latent fingerprint was also systematically investigated. These results suggest that the Ho<SUP>3+</SUP>-activated NaYbF<SUB>4</SUB> UCNPs are very promising as a bifunctional nanoparticle for <I>in vitro</I> cell imaging and latent fingerprint detection.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Under 980nm light excitation, the synthesized UCNPs emitted eye-visible emissions. </LI> <LI> The resultant UCNPs possessed low cell toxicity. </LI> <LI> The as-prepared UCNPs were suitable for live cell imaging. </LI> <LI> The synthesized UCNPs have promising application in latent fingerprint detection. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P> <I>In vitro</I> upconversion luminescence imaging of HeLa cells under the irradiation of 980nm light; Photographs of latent fingerprint stained by NaYbF<SUB>4</SUB>:Ho<SUP>3+</SUP> UCNPs under 980nm light excitation.</P> <P>[DISPLAY OMISSION]</P>

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>

대호 간척기 토양의 염농도별 밭작물의 염해 평가

이승헌,류순호,설수일,안열,정영상,이상모 江原大學校 附設 環境硏究所 2001 環境硏究 Vol.18 No.-

This study was carried out to obtain the basic data for selecting the applicable crops in reclaimed land during desalinization period. A pot experiment was conducted with 5 different electrical conductivities of the saturated extracts (ECe 1, 3, 9, 14, and 16 dS·m^(-1)) of soils taken from the Dae-Ho reclaimed tidal lands. Eight crops (Chinese cabbage, radish, tomato, red pepper, buckwheat, soybean, sesame, and green perilla) were grown for 37days. Plant height and number of leaves were surveyed on 2 and 4 weeks after seeding, and on harvest time (5 weeks). After harvest, dry weights of harvested crops were measured and soil chemical properties were analyzed. Emergence rates of crops were comparatively high except sesame. For sesame, there was no emergence at ECe over 3 dS·m^(-1). Growth and dry weight decreased significantly as increasing ECe. The ECe which decreased 50% of dry weight index were 14.2 dS·m^(-1) for radish, 11.4 dS·m^(-1) for Chinese cabbage, 10.2 dS·m^(-1) for tomato for red pepper, 8.9 dS·m^(-1) for buckwheat and green perilla, 8.6 dS·m^(-1) for soybean, and 8.9 dS·m^(-1) for tomato. At higher ECe that start the growth inhibition, increasing 1 dS·m^(-1) in ECe, 7.7, 6.5, 5.9, 5.6, 5.2, and 4.9% of dry weight decreased for buckwheat, green perilla, Chinese cabbage, radish, soybean, and tomato (red pepper), respectively. The critical value of ECe for crop survival except sesame was 15.4~23.1 dS·m^(-1).

Wireless pressure sensor integrated with a 3D printed polymer stent for smart health monitoring

Park, Jongsung,Kim, Ji-Kwan,Kim, Dong-Su,Shanmugasundaram, Arunkumar,Park, Su A,Kang, Sohi,Kim, Sung-Ho,Jeong, Myung Ho,Lee, Dong-Weon Elsevier 2019 Sensors and actuators. B Chemical Vol.280 No.-

<P><B>Abstract</B></P> <P>The primary objective of this study was to deploy a promising wireless pressure sensor system capable of monitoring real-time biological signals in an experimental object. MEMS-based micromachining technology was used to fabricate the proposed SU-8 wireless pressure sensor. The sensor utilizes a capacitor-inductor resonant circuit that can operate the sensor without any external power supply. The variable capacitor in the pressure sensor is designed to change the resonance frequency (130, 183 MHz) in response to applied pressure. The fabricated wireless pressure sensor was integrated into a polymer-based smart stent to minimize the discomfort of medication administration and hospital visits. A 3D bio-printing-based manufacturing technique was employed for the production of a smart polymer stent with complicated shapes. The proposed method is considerably more comfortable than the conventional metal stents fabrication process. The polymer smart stent made of the biocompatible polycaprolactone (PCL) material which can be fully absorbed by the body after a medication period. After integrating the fabricated wireless pressure sensor with the polymer smart stent, various basic experiments such as the working distance of the sensor were performed using a simple experimental setup. The biocompatibility of the proposed polymer stent and the wireless pressure sensor was also successfully confirmed using an experimental animal. The preliminary investigation results indicate that the proposed wireless sensor can be used to obtain necessary information in various parts of the human body as well as the stent.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Fabrication of SU-8 based wireless pressure sensor for battery-less operation. </LI> <LI> Manufacturing of biodegradable polymer stent using 3D printing technique. </LI> <LI> Integration of wireless pressure sensor into polymer stent for real-time blood pressure monitoring. </LI> <LI> Verification of the biocompatibility of smart stent and its operation with experimental animals. </LI> <LI> Continuous measurement of blood pressure change in animals for more than 3 months. </LI> </UL> </P>

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>