• Title/Summary/Keyword: islet

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Transdifferentiation of α-1,3-Galactosyltransferase Knock Out (GalT KO) Pig Derived Bone Marrow Mesenchymal Stromal Cells (BM-MSCs) into Pancreatic Cells by Transfection of hPDX1 (hPDX1 유전자의 삽입에 의한 직접 췌도세포 분화)

  • Ock, Sun A;Oh, Keon Bong;Hwang, Seongsoo;Kim, Youngim;Kwon, Dae-Jin;Im, Gi-Sun
    • Journal of Embryo Transfer
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    • v.30 no.3
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    • pp.249-255
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    • 2015
  • Diabetes mellitus, the most common metabolic disorder, is divided into two types: type 1 and type 2. The essential treatment of type 1 diabetes, caused by immune-mediated destruction of ${\beta}-cells$, is transplantation of the pancreas; however, this treatment is limited by issues such as the lack of donors for islet transplantation and immune rejection. As an alternative approach, stem cell therapy has been used as a new tool. The present study revealed that bone marrowderived mesenchymal stromal cells (BM-MSCs) could be transdifferentiated into pancreatic cells by the insertion of a key gene for embryonic development of the pancreas, the pancreatic and duodenal homeobox factor 1 (PDX1). To avoid immune rejection associated with xenotransplantation and to develop a new cell-based treatment, BM-MSCs from ${\alpha}$-1,3-galactosyltransferase knockout (GalT KO) pigs were used as the source of the cells. Transfection of the EGFP-hPDX1 gene into GalT KO pig-derived BM-MSCs was performed by electroporation. Cells were evaluated for hPDX1 expression by immunofluorescence and RT-PCR. Transdifferentiation into pancreatic cells was confirmed by morphological transformation, immunofluorescence, and endogenous pPDX1 gene expression. At 3~4 weeks after transduction, cell morphology changed from spindle-like shape to round shape, similar to that observed in cuboidal epithelium expressing EGFP. Results of RT-PCR confirmed the expression of both exogenous hPDX1 and endogenous pPDX1. Therefore, GalT KO pig-derived BM-MSCs transdifferentiated into pancreatic cells by transfection of hPDX1. The present results are indicative of the therapeutic potential of PDX1-expressing GalT KO pig-derived BM-MSCs in ${\beta}-cell$ replacement. This potential needs to be explored further by using in vivo studies to confirm these findings.

Immunohistochemical study of the pancreatic endocrine cells in the ICR mice (ICR 마우스 췌장 내분비세포에 대한 면역조직화학적 연구)

  • Ku, Sae-kwang;Lee, Hyeung-sik;Lee, Jae-hyun
    • Korean Journal of Veterinary Research
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    • v.42 no.1
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    • pp.21-28
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    • 2002
  • The regional distribution and relative frequency of the pancreatic endocrine cells in the ICR mouse were studied by immunohistochemical (PAP) method using four types of specific antisera against insulin, glucagon, somatostatin and human pancreatic polypeptide (PP). The pancreas of mice could be divided into three portions; pancreatic islets, exocrine and pancreatic ducts. Pancreatic islets, furthermore, were subdivided into three regions (central, mantle and peripheral region) according to their located types of immunoreactive cells. In the pancreatic islet portions, insulin-immunoreactive cells were located in the central and mantle regions but most of somatostatin-, glucagon- and PP-immunoreactive cells were detected in the mantle and peripheral regions with various frequencies. In addition, PP-immunoreactive cells were also found in the central regions of pancreatic islets of ICR mouse. In the exocrine portions, all four types of immunoreactive cells were demonstrated in the ICR mouse. In the pancreatic duct portions, insulin- and glucagon-immunoreactive cells were situated in the epithelial lining of ICR mouse with a few and rare frequencies, respectively. In addition, rare PP-immunoreactive cells were also demonstrated in the subepithelial regions of the pancreatic duct. However, no somatostatin-immunoreactive cells were demonstrated.

Effects of Nelumbo Folium and Hayopokchun-san on Diabetes Mellitus in Streptozotocin Treated Rats (하엽(荷葉) 및 하엽옥천산(荷葉玉泉散)이 streptozotocin으로 유발된 당뇨(糖尿)에 미치는 영향)

  • Yang, Woong-Mo;Chang, Mun-Seog;Park, Wan-Su;Lee, Byong-Hee;Kim, Won-Nam;Kim, San-Woong;Choi, Dong-Gi;Lee, Hak-Chul;Park, Seong-Kyu
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1497-1501
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    • 2006
  • The therapeutic anti-diabetic effect of Nelumbo Folium and a poly herbal formula (NOC) was evaluated in the streptozotocin (STZ 60 mg/kg, I.p.) induced diabetic rats. For this study, test articles were orally administrated once a day from 7 d after STZ-injection for 3 weeks. The fasting blood glucose, body weight, pancreas weight changes, oral glucose tolerance test, hemoglobin Alc (Hb A1c) level changes and the histopathological changes were observed. WNL-treated rat had lower fasting blood glucose levels compared to control group and NOC-treated rat had significantly lower fasting blood glucose levels, compared to control group (p < 0.05). After 21 days of extract treatment, body weight in control was reduced (p < 0.001). WNL and NOC groups were also reduced compared to control group but insignificantly. Pancreas weight of control group was reduced (p < 0.001), but the weight of NOC group were increased (P< 0.05). During the 2 h oral glucose tolerance test (OGTT), WNL group were improved compared to control group (P < 0.05). NOC group were improved compared to control group but insignificantly. WNL and NOC groups had lower Hb Alc level compared to control group. In addition, atrophy of islet and decrease of insulin-producing cells were detected in STZ induced diabetes rats. However, these diabetic changes were decreased in WNL and NOC groups. These results suggest that N. Folium and NOC have favorable effects to inhibit the changes on the fasting blood glucose levels, pancreas weight, glucose tolerance, hemoglobin Alc and the histopathological changes of pancreas in STZ-induced diabetes.

Expression of c-Jun N-Terminal Kinase (JNK)-Interacting Protein (JIP) in Cultured Rat Hippocampal Neurons (배양한 흰쥐 해마신경세포에서 c-Jun N-terminal kinase (JNK)-interacting protein (JIP)의 표현)

  • Moon, Il-Soo
    • Journal of Life Science
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    • v.17 no.12
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    • pp.1627-1633
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    • 2007
  • c-Jun N-terminal kinase (JNK)-interacting protein 1 (JIP1), also known as Islet-brain 1 (IB1), is a scaffold protein that is highly expressed in neurons and pancreatic ${\beta}-cells$. In this study subcellular localization of JIP was investigated in cultured rat hippocampal neurons using an antibody that recognize all variants of JIP1, JIP-2 and JIP-3. The overall expression profile of JIP is punctate throughout soma and dendrites. Statistic analysis showed that $54.8{\pm}4.0%\;and\;94.1{\pm}4.5%$ of total JIP immunopuncta overlapped with those of excitatory postsynaptic markers SD-95 and ${\alpha}Camik$, respectively. In contrast, only $8.6{\pm}0.5%\;and\;7.3{\pm}0.5%$ of JIP clusters overlapped with those of inhibitory postsynaptic markers glycine receptor (GlyR) and gephyrin, respectively. JIP clusters overlapped or juxtaposed with SV2 but not GAD, markers for general and inhibitory nerve terminals, respectively. A substantial fraction $(29.3{\pm}1.0%)$ of flotillin immunopuncta, a marker for lipid rafts, clusters overlapped with those of JIP. In addition, JIP was highly expressed in some select ends of dendrites but minimal in axons. These data suggest important roles of JIP in excitatory postsynaptic sites, lipid rafts and dendritic ends.

A Study of the Macrozoobenthos at the Intensive fish Fanning Grounds in the Southern Coast of Korea (남해안 가두리 양식장 밀집해역의 대형저서동물 군집에 대한 연구)

  • 정래홍;임현식;김성수;박종수;전경암;이영식;이재성;김귀영;고우진
    • The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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    • v.7 no.4
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    • pp.235-246
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    • 2002
  • The fish farming using net cages has been developed in many semi-closed bays in the southern coast of Korea for the last two decades. The intensive cage cultures of fishes generate considerable amounts of organic waste in the form of uneaten food and faeces. In order to evaluate the effect of fish farming activities we collected the benthic macrofauna near the fish farm area located in Wolho Islet of Gamak Bay and in Haklim Island of Tongyeong in November 1998. Benthic macrofaunal assemblages showed dramatic changes in species number, species diversity, and faunal abundance in the region of the fish farm. These changes were clearly observed even at a distance of up to 30 m from the fish farming cage area. Within 5 m from the cage, there was a zone with low species diversity and highest density, dominated by opportunistic polychaete worm, Capitella capitata. By a distance of 15-30 m, this zone presents highest species number and higher density. Our results clearly demonstrated that fish farm area was highly enriched with organic materials, and implied that the fish farm industry and adjacent benthic ecosystem in semi-closed bay will be seriously damaged by self produced organic wastes in the near future.

A Study on the Change of Pond in the Jongmyo Shrine (종묘 지당(池塘)의 변천(變遷)에 관한 연구)

  • Oh, Jun-young;Kim, Young-mo
    • Korean Journal of Heritage: History & Science
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    • v.49 no.4
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    • pp.64-79
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    • 2016
  • The purpose of the present study is to clarify the process of change to the pond at the Jongmyo Shrine(宗廟), from the Joseon Dynasty period to the modern and contemporary era. The consequent research results can be summarized as follows. The first record of the Jongmyo pond is confirmed in the "Annals of King Sejong(世宗實錄)". The pond, which was being constructed at the time, refers to the current upper pond(上池). A pair of islets(雙島) were constructed during the Sukjong(肅宗) period, with several trees planted on the middle islet(中池). The middle pond is thick with lotuses. In particular, the middle island on the middle pond subsequently changed into a single island(單島), which is likely to be related to the pond expansion during the reign of Youngjo(英祖). When the lower pond(下池), involving dualistic arrangement, was constructed in the modern and contemporary era, the pond of the Jongmyo Shrine underwent a drastic transformation phase. The lower pond was constructed before 1947 at the latest, and when the right side of the lower pond was filled in the mid 1980s, the dualistically arranged lower pond became a unified type of lower pond. On the other hand, the bank protections of the upper and middle ponds were constructed with earth, but was subsequently modified into its current form using stone.

In vivo multiplex gene targeting with Streptococcus pyogens and Campylobacter jejuni Cas9 for pancreatic cancer modeling in wild-type animal

  • Chang, Yoo Jin;Bae, Jihyeon;Zhao, Yang;Lee, Geonseong;Han, Jeongpil;Lee, Yoon Hoo;Koo, Ok Jae;Seo, Sunmin;Choi, Yang-Kyu;Yeom, Su Cheong
    • Journal of Veterinary Science
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    • v.21 no.2
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    • pp.26.1-26.14
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    • 2020
  • Pancreatic ductal adenocarcinoma is a lethal cancer type that is associated with multiple gene mutations in somatic cells. Genetically engineered mouse is hardly applicable for developing a pancreatic cancer model, and the xenograft model poses a limitation in the reflection of early stage pancreatic cancer. Thus, in vivo somatic cell gene engineering with clustered regularly interspaced short palindromic repeats is drawing increasing attention for generating an animal model of pancreatic cancer. In this study, we selected Kras, Trp53, Ink4a, Smad4, and Brca2 as target genes, and applied Campylobacter jejuni Cas9 (CjCas9) and Streptococcus pyogens Cas9 (SpCas9) for developing pancreatic cancer using adeno associated virus (AAV) transduction. After confirming multifocal and diffuse transduction of AAV2, we generated SpCas9 overexpression mice, which exhibited high double-strand DNA breakage (DSB) in target genes and pancreatic intraepithelial neoplasia (PanIN) lesions with two AAV transductions; however, wild-type (WT) mice with three AAV transductions did not develop PanIN. Furthermore, small-sized Cjcas9 was applied to WT mice with two AAV system, which, in addition, developed high extensive DSB and PanIN lesions. Histological changes and expression of cancer markers such as Ki67, cytokeratin, Mucin5a, alpha smooth muscle actin in duct and islet cells were observed. In addition, the study revealed several findings such as 1) multiple DSB potential of AAV-CjCas9, 2) peri-ductal lymphocyte infiltration, 3) multi-focal cancer marker expression, and 4) requirement of > 12 months for initiation of PanIN in AAV mediated targeting. In this study, we present a useful tool for in vivo cancer modeling that would be applicable for other disease models as well.

Flavonol glycosides from the flowers of Carthamus tinctorius and their anti-diabetic activity (잇꽃(Carthamus tinctorius)으로부터 Flavonol glycoside 화합물들의 분리 및 항당뇨 효과)

  • Bo-Ram Choi;Hyoung-Geun Kim;Yoon Hee Nam;Dahye Yoon;Woo Cheol Shin;Jin-Kyu Jang;Yunji Lee;Tong Ho Kang;Nam-In Baek;Dae Young Lee
    • Journal of Applied Biological Chemistry
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    • v.66
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    • pp.477-483
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    • 2023
  • The flowers of Carthamus tinctorius (Safflower) were extracted with 80% aqueous methanol (CTex) and the concentrates were partitioned into EtOAc (CTE), n-BuOH (CTB), and H2O (CTW) fractions. Repeated silica gel (SiO2) and octadecyl silica gel column chromatographies for the EtOAc and n-BuOH fractions led to isolation of four flavonol glycosides. Nuclear magnetic resornance, infrarad spectroscopy, and mass spectroscopy revealed the chemical structure of the isolated compounds, astragalin (1), isoquercetin (2), nicotiflorin (3), and rutin (4). Quantitative analysis of four isolated compounds in CTex was performed by HPLC. CTex was found to contain 1 at 0.107, 2 at 0.367, 3 at 6.752, and 4 at 0.991 mg/g, respectively. Through this study, an experiment was conducted to evaluate the protective effect on pancreatic islets of the extract, solvent fractions, and all isolated compounds using a zebrafish larvae damaged by alloxan. Pancreatic islet size treated with EtOAc (CTE), n-BuOH (CTB), and H2O (CTW) fractions and compounds 1-4 significantly increased compared to the alloxan-induced group. These results indicate that C. tinctorius flowers and its isolated compounds are used as potential anti-diabetic agents.

A Study on the Breeding Density and Diet of Magpie Pica pica in Jeju Island1a (제주도에 서식하는 까치 Pica pica의 번식 밀도 및 식이물에 관한 연구)

  • Park, Joo-Yeon;Kim, Byoung-Soo;Oh, Hong-Shik
    • Korean Journal of Environment and Ecology
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    • v.22 no.6
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    • pp.648-657
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    • 2008
  • This research was conducted to investigate the breeding density and seasonal food items of the magpies in Jeju Island and the near-manned islets. The examination of nest distribution to determine breeding density was performed during breeding season from February 2006 to April 2008, and that of food items from May 2006 to February 2008. A total of 2,113 nests were found across Jeju Island, the average density was $1.33\;nest/km^2$, and the magpies were distributed up to 600 meters above the sea level. The nest density was the highest in the central areas of Jeju Island, with 688 nests at $3.61\;nest/km^2$, while that in the eastern areas was the lowest, with 214 nests at $0.66\;nest/km^2$. In terms of the number of nests depending on the height above the sea level, 1,172 nests, which was equivalent to the density of $1.85\;nest/km^2$, was observed below 100m and highest among the intervals of height, but 16 nests found at 500-600m were the lowest, corresponding to $0.20\;nest/km^2$. The number of nests found in the manned islets near Jeju Island was eight in Biyang-do with the density of $15.38\;nest/km^2$, nine in U-do with $1.49\;nest/km^2$, and one in Gapa-do with $1.15\;nest/km^2$, whereas none of nests were observed in Mara-do. The contents of stomach consisted of 17 types of prey sources including countless bones, eggshells, plants, and seed, most of which were the individuals of the order Coleoptera. In spring and summer, the foraging frequency for invertebrate animals such as insects was high, but less than 30% in winter. In contrast, the magpies preyed upon plants and seeds at the frequency of 10% and 30%, respectively, in spring, while the foraging frequencies for both of them were 100% in winter and higher than any of other seasons. Eggshells and bones of birds were also detected infrequently. If the density of the magpies, which may play role as the upper predator within the ecosystem, increases, it would be expected to affect directly the reduction of the number of the species and population of endemic animals such as small birds and reptiles, etc. Therefore, it is considered that long-term monitoring for the density of the magpies and precaution is prerequisite to minimize adverse effects on ecosystem.

Growth Pattern of Red-tongued Viper Snake (Gloydius ussuriensis) Inhabiting Gapado, Jeju Island (가파도에 서식하는 쇠살모사의 성장 패턴)

  • Kim, Byoung Soo;Chang, Min-Ho;Oh, Hong Shik
    • Journal of Environmental Impact Assessment
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    • v.25 no.6
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    • pp.477-486
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    • 2016
  • We investigated the growth pattern of Red-tongued viper snakes (Gloydius ussuriensis), which were captured from the islet of the Jeju Island, Gapado between April, 2006 and November, 2009. The results indicated that there were some snakes that grew relatively fast, but most snakes either almost did not grow or grew around 10mm in snout-vent length during one year period. High growth rates was April and June. Since the growth rate of snakes is highly correlated with their foods, these results implied that the feeding activity of Red-tongued viper snakes is high during this period compared to other months. In female, difference in body condition between good-conditioned and bad-conditioned snakes became large as time elapsed from April to June. The body condition of the male Red-tongued viper snakes improved with the progression of time from April till June. Many of the Red-tongued viper snakes were captured between April and June, while they were rarely captured between July and September. Some of the Red-tongued viper snakes were captured during the autumn season. This tendency was because snakes were rarely active during hibernation and peak summer seasons. Thus, Red-tongued viper snakes are active between April and June and between September and November. They then go into hibernation as the temperature dropped in November. Furthermore, the limitation of the movement period of the Red-tongued viper snakes restricted their feeding activities while foods became scarce, which ultimately restricted their overall growth rate. The growth rate of the snakes decreased with age. The snout-vent length of the Red-tongued viper snakes and growth rate showed a negative correlation (r = -0.591), however, it was not statistically significant due to small sample size. The findings from this study could provide meaningful information in the further study of the life cycle of Red-tongued viper snakes.