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Biodistribution of [S-35] Labeled Antisense Oligodeoxynucleotides Increased Tumor Targeting With Microsphere Coinjection

  • Choe, Jae-Gol;Park, Gil-Hong;Claudio Nastruzzi;Yoon S. Cho-Chung;Kim, Meyoung-Kon
    • Environmental Mutagens and Carcinogens
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    • v.22 no.2
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    • pp.65-69
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    • 2002
  • To elucidate the effect of microsphere coinjection on the administration of oligodeoxynucleotides (ODN), we have investigated biodistribution of [S-35]-labeled antisense ODN targeted to cAMP-dependent protein kinase (PKA) RI-$\alpha$ subunit in nude mice xenografted with WiDr (human colon cancer, ATCC CCL218). The strategy of using microsphere has been proposed for cancer treatment as a carrier of therapeutic ODN so that it could offer an advantage with respect to maintaining constant ODN levels in blood and obtaining higher therapeutic ODN concentration at tumor sites. Comparative biodistribution studies were performed in nude mice (female, 20 g of body weight, n = 4-6) xenografted with WiDr cancer cells, when 0.1 $\mu$Ci (specific activity, 2.94 mCi/$\mu$mole) of [S-35]-labeled RI-$\alpha$ antisense ODN was injected alone or with microsphere (PLG-18, polylactic copolymer with cationic surfactant DDAB18). Peak tumor uptake of [S-35]-labeled ODN was significantly increased from 17.7% (at 6 h) of injected dose per gram of tissue (ID/g) to 42.5% (at 24 h) ID/g when microsphere was coinjected with ODN. The different biodistribution in the kidney accumulation (e.g., 100.2% ID/g for ODN alone and 54.9%/ID/g for microshpere coinjection) may contribute to higher blood concentration (e.g., 21.5%ID/$m\ell$ for ODN alone and 37.5%ID/$m\ell$ for microsphere coinjection) of radiolabeled ODN. Of importance is the fact that the whole body retention of radioactivity increased with microsphere coinjection from 50.8%ID/g to 68.0%ID/g after 24-h of injection. This decreased kidney accumulation and increased whole body retention of [S-35]-labeled ODN resulted in a significant improvement of ODN targeting to the tumor site. In conclusion, the coinjection of microsphere appears to be an important carrier system in vehiculation of antisense oligonucleotide to the tumor tissue in vivo.

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The Effect of Laserpuncture and Aquapuncture with Methionine on the Recovery in Artificially Induced Hepatic Damaged Rats (肝損傷 랫트에 있어서 Laser針療法 및 Methionine 水針療法이 肝損傷 回復에 미치는 影響)

  • 홍민성;이지영;이버들;이상은;서지민;송근호;김덕환;조규완;김명철
    • Journal of Veterinary Clinics
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    • v.19 no.2
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    • pp.125-131
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    • 2002
  • The present experiment was performed in order to know the therapeutic effect of laserpuncture and aquapuncture with methionine on recovery in artificially induced hepatic damaged rats by carbon tetrachloride. The animals were divided into control, laserpuncture and aquapuncture groups. The changes of serum enzyme activities(ALT and AST), serum total protein contents, protein fractions(ALB and GLB) and A/G ratio were examined before and after application of laserpuncture and aquapuncture. In change of serum ALT activity, recovery with treatment in laser and aquapuncture groups was more rapid than that of control. The significant decreased value was shown on 3rd(P < 0.05) and 7th day(P < 0.01) after treatment in laserpuncture group and on 7th day(P < 0.05) after treatment in aquapuncture group. In addition, significance was detected on 2nd day(P < 0.05) between laserpuncture and aquapuncture groups. In change of serum AST activity, recovery with treatment in laserpuncture and aquapuncture groups was more rapid than that of control. The significant lower values on 7th day(P<0.01) in aquapuncture groups. In addition, significant low value was detected on 7th day(P < 0.05) in aquapuncture group comparing with that of laserpuncture group. The change of serum TP contents showed similar pattern in control, laser and aquapuncture groups. The significances were detected on 7th day(P < 0.05) in both experimental groups. In addition, significant high value was detected on 2nd day(P < 0.05) in laserpuncture group comparing with that of aquapuncture group. The change of serum ALB content with treatment in laser and aquapuncture groups was more rapid than that of control. The significant high value was shown on 2nd(P < 0.01), 5th(P < 0.05) and on 7th day(P < 0.01) in laserpuncture group. In addition, significant high value was detected on 3rd day(P<0.01) only in aquapuncture group comparing with laserpuncture group. The change of serum GLB content showed similar pattern among groups. The significant low values were detected on 2nd day(P < 0.05) in aquapuncture group. In addition significant high value was detected on 5th day(P < 0.01) only in laserpuncture group comparing with that of aquapuncture group. In change of A/G ratio laser and aquapuncture groups showed higher values than that of control. The significant high values were detected on 1st day(P < 0.Of) and 2nd day(P < 0.05) in laserpuncture group, and on 1st day(P < 0.05) and 2nd day(P < 0.01) in aquapuncture group. In addition, significant high value was detected on 5th day(P < 0.05) in aquapuncture group comparing with that of laserpuncture. Considering above findings collectively, it was considered that both laserpuncture and aquapuncture were effective; aquapuncture was more effective than laserpuncture for recovery of hepatic damage.

Cellular-protective effects of Nardotidis seu Sulculii Concha Extract against oxidative stress (산화적 스트레스에 대한 석결명의 세포 보호 효과)

  • Kim, Kwang Yeon;Lee, Seung Jin;Jee, Seon Young;Bae, Su Jin;Song, Yu Rim;Yun, Un-Jung;Bak, Seonbeen;Song, Jong Kuk;Son, Tae Jin;Son, Jae-Dong;Kim, Woo Hyun;Yang, Ju Hye;Park, Sun Dong;Kim, Sang Chan;Kim, Young Woo;Park, Kwang-Il
    • Herbal Formula Science
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    • v.29 no.2
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    • pp.71-80
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    • 2021
  • Objectives : This study investigated cellular-protective effects of Nardotidis seu Sulculii Concha water extract (NSCE) against oxidative stress induced by arachidonic acid (AA)+iron or tert-butylhydroperoxide (tBHP). Methods : In vitro, MTT assay was assessed for cell viability, and immunoblotting analysis was performed to detect expression of AMP-activated kinase (AMPK) signaling pathway and autophagy related proteins. In vivo, mice were orally administrated with the aqueous extract of NSCE of 500 mg/kg for 3 days, and then injected with CCl4 0.5 mg/kg body weight to induce acute damage. The level of liver damage was measured by serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) analysis. Results : Treatment with NSCE inhibited cell death induced by AA+iron and tBHP. NSCE induced the phosphorylation of AMPK, and this compound also induced the phosphorylation of LKB1, an upstream kinase of AMPK, and Acetyl-CoA carboxylase (ACC), a primary downstream target of AMPK. NSCE increased the protein levels of autophagic markers (LC3II and beclin-1) and decreased the phosphorylation of mammalian target of rapamycin (mTOR) and simultaneously increased the phosphorylation of unc-51-like kinase-1 (ULK-1) in time-dependent manner. Conclusions : NSCE has the ability 1) to protect cells against oxidative stress induced by AA+iron or tBHP. NSCE 2) to activate AMP-activated protein kinase (AMPK), and 3) to regulate autophagy, an important regulator in cell survival.

Non-alcoholic fatty liver protective effects, and studies on the mechanism of action of Crataegi Fructus (산사의 NAFLD 보호 효과 및 그 작용기전에 관한 연구)

  • Kim, Min-Chul;Kong, Ryong;Han, Hyoung-Sun;Kang, Dam-hee;Lee, Seung-Jin;Lee, Cheon-Cheon;Wang, Seo;Kwon, Dong-Yeul;Kang, Ok-Hwa
    • The Korea Journal of Herbology
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    • v.33 no.6
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    • pp.61-70
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    • 2018
  • Objectives : Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of hepatic triglycerides (TG) that leads to inflammation and fibrosis. Crataegi Fructus ethanol extract (CE) is a korean traditional herb that used for digestive diseases. It has been investigated that CE has the effect that prevent hepatotoxicity caused by CCl4 or GaIN and regulate the inflammatory in several organs. However, a hypolipidemic effect of CF has not been reported. Methods : The purpose of this study is that examine the lipid accumulation inhibitory effect of CE on NAFLD. We checked the body and liver weight change of MCD-diet induced mice with/without administration of CE. The blood lipid levels of C57BL/6J mice were checked by biochemistry. Also we observed the liver histology of MCD-diet induced mice and investigate the molecular mechanisms in MCD-diet-induced NAFLD in C57BL/6J mice. Results : CE improved MCD-diet-induced lipid accumulation and TG and TC levels. Also, CE decreased hepatic lipogenesis such as SREBP-1, $C/EBP{\alpha}$, $PPAR{\gamma}$, ACC and FAS. Besides, we also found out that CE increased AMPK phosphorylation. These results indicated that CE has the same ability to activate AMPK and then reduce SREBP-1, and FAS expression, finally leading to inhibit hepatic lipogenesis and hepatic antioxidative ability. Conclusions : In this report, we found CE exerted a regulatory effect on lipid accumulation by decreasing lipogenesis in MCD-diet induced NAFLD model. Therefore, CE extract may be active in the prevention of fatty liver.

Photocatalytic effect for the carbon-coated TiO2 prepared from different heat treatment temperature (열처리 온도에 따라 제조된 탄소 코팅된 TiO2에 대한 광촉매 효과)

  • Chen, Ming-Liang;Bae, Jang-Soon;Oh, Won-Chun
    • Analytical Science and Technology
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    • v.19 no.6
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    • pp.460-467
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    • 2006
  • Carbon-coated $TiO_2$ was prepared by $CCl_4$ solvent mixing method with different heat treatment temperature (HTT). Since the carbon layers derived from pitch on the $TiO_2$ particles were porous, the carbon-coated $TiO_2$ sample series showed a good adsorptivity and photo decomposition activity. The BET surface area was decreased by the increasing of the heat treatment temperature. The SEM results present to the characterization of surface texture on the carbon-coated $TiO_2$ sample and carbon distributions on the surfaces for all the materials used. The main elements of C, O and Ti were shown from EDX spectra. And the quantity of these elements is very rich in the samples. From XRD data, the pristine anatase peaks were observed in the X-ray diffraction patterns for the carbon-coated $TiO_2$ at the different HTTs. However, the rutile peaks were observed for the carbon-coated $TiO_2$ at HTT of 1073 K and 1123 K. Finally, the excellent photocatalytic activity of carbon-coated $TiO_2$ with UV-vis spectra between absorbance and time could be attributed to the homogeneous coated carbon on the external surface and structural phase transform, and the photocatalytic activity was decreased by the increasing of the HTT.

Assessment of LCD Color Display Performance Based on AAPM TG 18 Protocol : Decision of Quality Control and Calibration Period (판독용 LCD 컬러 모니터 장치의 성능 평가 - 성능 평가 및 Calibration 주기 결정을 중심으로 -)

  • Lee, Won-Hong;Son, Soon-Yong;Noh, Sung-Soon;Lee, In-Hwa;Kang, Sung-Ho;Lee, Yong-Moon;Park, Jae-Soo;Yoon, Seok-Hwan
    • Journal of radiological science and technology
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    • v.31 no.1
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    • pp.55-60
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    • 2008
  • Purpose: This study is to decide a quality control and calibration period of LCD display devices used for reading diagnostic images. Materias and Methods: The assessment test of 20 flat panel LCD color display devices used for reading diagnostic images were performed based on AAPM TG 18 protocol over the total six sessions at one month intervals from three months after primary calibration, in terms of geometric distortion, reflection test, luminance response evaluation, luminance uniformity, resolution, noise, veiling glare and chromaticity test. Results: The results of geometric distortion, reflection test, luminance uniformity, resolution, noise, veiling glare and chromaticity test were within the criteria recommended by AAPM TG 18, except for luminance response evaluation. In the measured luminance deviation of luminance response evaluation, 4(25%) of 20 display devices were passed a criterion from four months after calibration, and 11 (55%) were passed from eight months. Also in the contrast response of the luminance response evaluation, 1(5%) display device was passed a criterion from four months after calibration, and 3(15%) were passed from eight months. Conclusion: Considering the passing deviation after calibration, the time required and a manpower, the quality control and calibration period of LCD display devices used for reading diagnostic images should be a three months and six months after calibration.

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A Study on the Distribution and Conservation Plan of Vascular Flora in Gyodong Island (교동도의 관속식물상 분포 및 보전방안 연구)

  • Yun, Ho-Geun;Kim, Sang-Jun;Lee, Jong-Won
    • Journal of Environmental Impact Assessment
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    • v.31 no.1
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    • pp.11-46
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    • 2022
  • This study was carried out to examine vascular plants and invasive alien plants in Gyodong Island, located at the northwestern Civilian Control Line (CCL) of Ganghwa-gun, Incheon, and to use them as basic data for systematic management of identified plants and establishing biodiversity conservation measures. The survey was conducted 13 times from April 2019 to August 2021. The vascularflora in Gyodong Island was identified as 109 families, 378 genera, 641 species, 15 subspecies, 49 variants, 8 forma, a total of 713 taxa. This was found to be about 15.36% of the total 4,641 taxa of vascular plants in Korea. The northern linage plants on the Korean Peninsula appearing in the Gyodong Island area were identified in 83 classification groups, including Red-based leaf edge (Carex erythrobasis H.Lev. & Vaniot). Korea endemic plants were identified as 16 taxa such as Seoul wild-ginger [Asarum heterotropoides var. seoulense (Nakai) Kitag.], and a total of 20 taxa of rare plants designated by IUCN were observed, including the endangered grade Beardless iris (Iris ruthenica Ker Gawl.). Floristic target species were classified with a total of 99 taxa. For V grade, Beardless iris 1 taxon was found. and also IV grade and III grade were identified in 8 taxa and 20 taxa respectively. The invasive alien plants identified as 75 taxa, such as Verbesina alternifolia (L.) Britton ex Kearney. The naturalization rate was 10.51%, and the urbanization index was calculated as 23.29%. Since large-scale construction has been currently underway on Hwagae Mt. in Gyodong Island as the target of survey area, the influx of invasive plants will be expected to promote. Therefore, it is urgent to establish in-situ protection and conservation measures for notable plants such as Beardless iris and Water smartweed [Persicaria amphibia (L.) S.F.Gray].

The Efficacy Evaluation of Tourmaline-Ionized Water in Animal Study (투어마린이온활성수의 효능 평가)

  • Yoon, Yang-Suk;Kim, Dong-Heui;Qi, Xu-Feng;Song, Soon-Bong;Jung, Jong-Ho;Joo, Kyung-Bok;Teng, Yung-Chien;Lee, Kyu-Jae
    • Applied Microscopy
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    • v.39 no.4
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    • pp.311-317
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    • 2009
  • This study was performed using animals to confirm the effect of tourmaline-ionized water (TIW) the properties of which were changed by tourmaline energy and electric discharge. In the ICR mice fed high-fat diet, body weight increasing rate of the TIW-treated group (Exp) was generally decreased and moreover exhibited significance at 11th week (P<0.05) compared with the control (Con) group fed distilled water, although water intake of the Exp group was lower than that of the Con group. In the ICR mice with $CCl_4$-induced hepatotoxicity, AST and ALT activities of the Exp group were not significant but showed some decreasing trend, and histological damage of liver was less compared with thatof the Con group. On the study of ethanol-induced hangovers in Sprague-Dawley rat, blood alcohol concentration was significantly decreased (P<0.01), activity of GST, antioxidant enzyme related to the alcohol metabolism, was increased in liver tissue (P<0.05), and AST and ALT show a tendency to be decreasedin the Exp group. These results suggest that drinking TIWhas not only some obesity preventing effect but also an alcohol detoxification effect and liver protecting effect in vivo. It is supposed due to a structural change of water cluster and a property which maintains the changed structure through tourmaline energy and electric discharge. Therefore, TIW has a potentiality to be developed as functional water with several beneficial effects as well as for daily drinking, but further study on the mechanism related with efficacy will be necessary.

The Ecological Values of the Korean Demilitarized Zone(DMZ) and International Natural Protected Areas (비무장지대(DMZ)의 생태적 가치와 국제자연보호지역)

  • Cho, Do-soon
    • Korean Journal of Heritage: History & Science
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    • v.52 no.1
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    • pp.272-287
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    • 2019
  • The Korean Demilitarized Zone (DMZ) was established in 1953 by the Korean War Armistice Agreement. It extends from the estuary of the Imjin River, in the west, to the coast of the East Sea. It is 4 km in width and 148 km in length. However, the ecosystems of the civilian control zone (CCZ) located between the southern border of the DMZ and the civilian control line (CCL) and the CCZ in the estuary of the Han River and the Yellow Sea are similar to those in the DMZ, and, therefore, the ecosystems of the DMZ and the CCZ are collectively known as the "ecosystems of the DMZ and its vicinities." The flora in the DMZ and its vicinities is composed of 1,864 species, which accounts for about 42% of all the vascular plant species on the Korean Peninsula and its affiliated islands. Conducting a detailed survey on the vegetation, flora, and fauna in the DMZ is almost impossible due to the presence of landmines and limitations on the time allowed to be spent in the DMZ. However, to assess the environmental impact of the Munsan-Gaesong railroad reconstruction project, it was possible to undertake a limited vegetation survey within the DMZ in 2001. The vegetation in Jangdan-myeon, in Paju City within the DMZ, was very simple. It was mostly secondary forests dominated by oaks such as Quercus mongolica, Q. acutissima, and Q. variabilis. The other half of the DMZ in Jangdan-myeon was occupied by grassland composed of tall grasses such as Miscanthus sinensis, M. sacchariflorus, and Phragmites japonica. Contrary to the expectation that the DMZ may be covered with pristine mature forests due to more than 60 years of no human interference, the vegetation in the DMZ was composed of simple secondary forests and grasslands formed on former rice paddies and agricultural fields. At present, the only legal protection system planned for the DMZ is the Natural Environment Conservation Act, which ensures that the DMZ would be managed as a nature reserve for only two years following Korean reunification. Therefore, firstly, the DMZ should be designated as a site of domestic legally protected areas such as nature reserve (natural monument), scenic site, national park, etc. In addition, we need to try to designate the DMZ as a UNESCO Biosphere Reserve or as a World Heritage site, or as a Ramsar international wetland for international cooperation. For nomination as a world heritage site, we can emphasize the ecological and landscape value of the wetlands converted from the former rice paddies and the secondary forests maintained by frequent fires initiated by military activities. If the two Koreas unexpectedly reunite without any measures in place for the protection of nature in the DMZ, the conditions prior to the Korean War, such as rice paddies and villages, will return. In order to maintain the current condition of the ecosystems in the DMZ, we have to discuss and prepare for measures including the retention of mines and barbed-wire fences, the construction of roads and railroads in the form of tunnels or bridges, and the maintenance of the current fire regime in the DMZ.

Analysis of the Flora and Vegetation Community in Forest Genetic Resources Reserves (Mt. Daeseng, Juparyeong), Near the DMZ (DMZ 인근지역 산림유전자원보호구역(대성산, 주파령)의 식물상 및 식생군집분석)

  • Son, Ho-Jun;Kim, Young-Sol;Ahn, Chi-Ho;Park, Wan-Geun
    • Journal of Korean Society of Forest Science
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    • v.105 no.1
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    • pp.19-41
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    • 2016
  • This study examined the flora and community classification in the Forest Genetic Resources Reserves (FGRR) at Mt. Daeseng and Juparyeong to understand the degree of disturbance and the state of forest stand development within the Civilian Control Line (CCL) and to provide baseline data for preservation and management. Of the vascular plants dispersed throughout the study site, there were 98 families, 311 genera, 507 species, 6 subspecies, 65 varieties, and 10 forms, for a total of 588 taxa. Of these, 92 families, 290 genera, 459 species, 6 subspecies, 58 varieties, and 9 forms, for a total of 532 taxa of native plants, were determined to be dispersed around the FGRR at Mt. Daeseng, and 94 families, 259 genera, 364 species, 6 subspecies, 50 varieties, and 8 forms, for a total of 428 taxa of native plants, were confirmed to be dispersed around the FGRR at Juparyeong. There were 21 taxa of endemic Korean plants growing in the FGRR at Mt. Daeseng, with 14 taxa growing in the FGRR at Juparyeong. In terms of rare plants, 26 taxa were confirmed in the FGRR at Mt. Daeseng, and 10 taxa were confirmed in the FGRR at Juparyeong. A Cluster analysis was performed using vegetation data taken from 58 sample plots in each FGRR. The results showed a total of three representative community classifications from Mt. Daeseng: mixed mesophytic forest, Quercus mongolica-Acer pseudosieboldianum, and Quercus mongolica-Fraxinus rhynchophylla communities. Four representative community classifications were observed from Juparyeong: Quercus mongolica-broad leaved forest, Fraxinus rhynchophylla-broad leaved forest, Quercus mongolica, and Quercus communities. On the whole, the species diversity of the communities in Mt. Daeseng FGRR was greater than for the communities in Juparyeong FGRR. At Mt. Daeseng, the mixed mesophytic forest had the highest species diversity index at 1.590, while at Juparyeong, the Fraxinus rhynchophylla-broad leaved forest had the highest species diversity index at 1.319. These study results should serve as useful baseline data for future preservation and management of the demilitarized zone (DMZ) and the surrounding area.