• Title/Summary/Keyword: cell fate

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Surface Topographical Cues for Regulating Differentiation of Human Neural Stem Cells

  • Yang, Kisuk;Lee, Jong Seung;Lee, Jaehong;Cheong, Eunji;Lee, Taeyoon;Im, Sung Gap;Cho, Seung-Woo
    • Proceedings of the Korean Institute of Surface Engineering Conference
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    • 2016.11a
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    • pp.122.2-122.2
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    • 2016
  • Surface topographical cues has been highlighted to control the fate of neural stem cells (NSCs). Herein we developed a hierarchically patterned substrate (HPS) platform for regulating NSC differentiation. The HPS induced cytoskeleton alignment and highly activated focal adhesion in hNSCs as indicated by enhanced expression of focal adhesion proteins such as focal adhesion kinase (FAK) and vinculin. hNSCs cultured on HPS exhibited enhanced neuronal differentiation compared to flat group. We also developed a graphene oxide (GO)-based hierarchically patterned substrates (GPS) that promote focal adhesion formation and neuronal differentiation of hNSCs. Enhanced focal adhesion and differentiation of hNSCs on the HPS was reversed by blocking the ${\beta}1$ integrin binding and mechanotransduction-associated signals including Rho-associated protein kinase (ROCK) and extracellular-regulated kinase (ERK) pathway, which may suggest a potential mechanism of beneficial effects of HPS. In addition, hNSCs on the HPS differentiated into functional neurons exhibiting sodium currents and action potentials as confirmed by whole cell patch-clamping analysis. The hierarchical topography can direct differentiation of NSCs towards functional neurons, and therefore would be an important element for the design of functional biomaterials for neural tissue regeneration applications.

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The Epithelial-Mesenchymal Transition During Tooth Root Development

  • Kang, Jee-Hae;Park, Jin-Ho;Moon, Yeon-Hee;Moon, Jung-Sun;Kim, Sun-Hun;Kim, Min-Seok
    • International Journal of Oral Biology
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    • v.36 no.3
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    • pp.135-141
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    • 2011
  • Hertwig's epithelial root sheath (HERS) consists of bi-layered cells derived from the inner and outer dental epithelia and plays important roles in tooth root formation as well as in the maintenance and regeneration of periodontal tissues. With regards to the fate of HERS, and although previous reports have suggested that this entails the formation of epithelial rests of Malassez, apoptosis or an epithelial-mesenchymal transformation (EMT), it is unclear what changes occur in the epithelial cells in this structure. This study examined whether HERS cells undergo EMT using a keratin-14 (K14) cre:ROSA 26 transgenic reporter mouse. The K14 transgene is expressed by many epithelial tissues, including the oral epithelium and the enamel organ. A distinct K14 expression pattern was found in the continuous HERS bi-layer and the epithelial diaphragm were visualized by detecting the ${\beta}$-galactosidase (lacZ) activity in 1 week postnatal mice. The 2 and 4 week old mice showed a fragmented HERS with cell aggregation along the root surface. However, some of the lacZ-positive dissociated cells along the root surface were not positive for pan-cytokeratin. These results suggest that the K14 transgene is a valuable marker of HERS. In addition, the current data suggest that some of the HERS cells may lose their epithelial properties after fragmentation and subsequently undergo EMT.

Decomposition and $^{15}N$ Fate of Rice Straw in Paddy Soil

  • Lee, Jeong-Sam;Lee, Ho-Jin;Lee, Seung-Hun
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.47 no.2
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    • pp.132-136
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    • 2002
  • The rice straw managements are essential for maintaining soil fertility as well as reducing chemical fertilizer application in paddy field. A field experiment was conducted on moderately well draining alluvial paddy soil to investigate the decomposition pattern of rice straw. The mesh bags containing the rice straw harvested in the previous year were placed at soil surface and buried into around 10cm depth and recovered periodically for determining the straw decomposition. Pot experiments were conducted to investigate the fates of N released from $^{15}$ N-labeled rice straw under different levels of N fertilizer application. The overall decomposition patterns of rice straw were similar for the two incorporation depths in transplanted paddy field. The straw incorporated at transplanting date showed weight loss of about 50%, 70% and 90% after 2 months, 5 months, and 2 years, respectively. The decompositions of straw cell wall components showed somewhat different pattern. The decompositions of cellulose and silica were similar to that of dry weight while the decomposition of lignin was slower than that of cellulose and silica. N was released from rice straw 42% and 65 % of the initial N after one month and after five months, respectively. P release was faster than N release. Recoveries of rice straw-$^{15}$ N by rice plants were 10.2, 13.4 and 14.9% in 0, 120 and 240 mg N pot$^{-1}$ , respectively. Soil recoveries of rice straw $^{15}$ N were 17.3, 20.6 and 18.9% in 0, 120 and 240mg N pot$^{-1}$ , respectively.

Isopsoralen Induces Differentiation of Prechondrogenic ATDC5 Cells via Activation of MAP Kinases and BMP-2 Signaling Pathways

  • Li, Liang;Eun, Jae-Soon;Nepal, Manoj;Ryu, Jae-Ha;Cho, Hyoung-Kwon;Choi, Bo-Yun;Soh, Yun-Jo
    • Biomolecules & Therapeutics
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    • v.20 no.3
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    • pp.299-305
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    • 2012
  • Endochondral bone formation is the process by which mesenchymal cells condense to become chondrocytes, which ultimately form new bone. The process of chondrogenic differentiation and hypertrophy is critical for bone formation and as such is regulated by many factors. In this study, we aimed to indentify novel factors that regulate chondrogenesis. We investigated the possible role of isopsoralen in induction of chondrogenic differentiation in clonal mouse chondrogenic ATDC5 cells. Isopsoralen treatment stimulated the accumulation of cartilage nodules in a dose-dependent manner. Further, ATDC5 cells treated with isopsoralen were stained more intensely with Alcian blue than control cells, suggesting that isopsoralen increases the synthesis of matrix proteoglycans. Similarly, isopsoralen markedly induced the activation of alkaline phosphatase activity compared with control cells. Isopsoralen enhanced the expressions of chondrogenic marker genes such as collagen II, collagen X, OCN, Smad4 and Sox9 in a time-dependent manner. Furthermore, isopsoralen induced the activation of extracellular signal-regulated kinase (ERK) and p38 MAP kinase, but not that of c-jun N-terminal kinase (JNK). Isopsoralen significantly enhanced the protein expression of BMP-2 in a time-dependent manner. PD98059 and SB 203580, inhibitors of ERK and p38 MAPK, respectively, decreased the number of stained cells treated with isopsoralen. Taken together, these results suggest that isopsoralen mediates a chondromodulating effect by BMP-2 or MAPK signaling pathways, and is therefore a possible therapeutic agent for bone growth disorders.

Iron chelating agent, deferoxamine, induced apoptosis in Saos-2 osteosarcoma cancer cells (Saos-2 골육종 세포에서 iron chelating agent, deferoxamine에 의한 apoptosis 유도)

  • Park, Eun Hye;Lee, Hyo Jung;Lee, Soo Yeon;Kim, Sun Young;Yi, Ho Keun;Lee, Dae Yeol;Hwang, Pyoung Han
    • Clinical and Experimental Pediatrics
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    • v.52 no.2
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    • pp.213-219
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    • 2009
  • Purpose:Iron is a critical nutritional element that is essential for a variety of important biological processes, including cell growth and differentiation, electron transfer reactions, and oxygen transport, activation, and detoxification. Iron is also required for neoplastic cell growth due to its catalytic effects on the formation of hydroxyl radicals, suppression of host defense cell activities, and promotion of cancer cell multiplication. Chronic transfusion-dependent patients receiving chemotherapy may have iron overload, which requires iron-chelating therapy. We performed this study to demonstrate whether the iron chelating agent deferoxamine induces apoptosis in Saos-2 osteosarcoma cells, and to investigate the underlying apoptotic mechanism. Methods:To analyze the apoptotic effects of an iron chelator, cultured Saos-2 cells were treated with deferoxamine. We analyzed cell survival by trypan blue and crystal violet analysis, apoptosis by nuclear condensation, DNA fragmentation, and cell cycle analysis, and the expression of apoptotic related proteins by Western immunoblot analysis. Results:Deferoxamine inhibited the growth of Saos-2 cell in a time- and dose-dependent manner. The major mechanism for growth inhibition with the deferoxamine treatment was by the induction of apoptosis, which was supported by nuclear staining, DNA fragmentation analysis, and flow cytometric analysis. Furthermore, bcl-2 expression decreased, while bax, caspase-3, caspase-9, and PARP expression increased in Saos-2 cells treated with deferoxamine. Conclusion:These results demonstrated that the iron chelating agent deferoxamine induced growth inhibition and mitochondrial-dependent apoptosis in osteosarcoma Saos-2 cells, suggesting that iron chelating agents used in controlling neoplastic cell fate can be potentially developed as an adjuvant agent enhancing the anti-tumor effect for the treatment of osteosarcoma.

Studies on the postnatal development of the Leydig cell in rabbits (토끼에서 출생 후 고환간질세포의 발생에 관한 연구)

  • Tae, Hyun-Jin;Park, Young-Jae;Kang, Hyung-Sub;Kim, Nam-Soo;Park, Sang-Youel;Yang, Hong-Hyun;Ahn, Dong-Choon;Kim, In-Shik
    • Korean Journal of Veterinary Research
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    • v.45 no.3
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    • pp.325-334
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    • 2005
  • Changes in the rabbit Leydig cell from birth to adulthood were studied in New Zealand white rabbits of 1, 7, 21, 35, 49, 70, 105, 147, 196, and 252 days (n = 8 rabbits per group) of age. The objectives of this study were to understand the fate of the fetal Leydig cells, to determine the changes in serum testosterone levels, and leutenizing hormone-stimulated testosterone production per testis in vitro, and to quantify adult Leydig cells by number and average volume with age. Testes of rabbits were fixed by whole body perfusion using a fixative containing 2.5% glutaraldehyde in cacodylate buffer, processed and embedded in Epon-araldite. Using $1{\mu}m$ sections stained with methylene blue-azure II, qualitative and quantitative (stereological) morphological studies were performed. Testosterone levels in the incubation medium of luteinizing hormone-stimulated (100 ng/ml) testosterone secretion per testis in vitro, and in serum were determined by radioimmunoassay. The average volume of a testis of 1-day-old rabbits was determined as $0.0073cm^3$ and the parameter increased linearly from birth to 252 days ($3.93cm^3$). The volume density of the seminiferous tubules increased with age from 33.76% at day 1 to 88.2% at day 252. The volume density of the interstitium represents 66.24% of the testicular parenchyma at day 1. This proportion progressively diminished during development to reach a value of 11.8% at day 252. The volume density of Leydig cells increased almost linearly from birth (0.001%) to 252 days (2.62%). Leydig cell mass per testis increases from 0.0012 mg to 0.25 mg between days 1 and 35, from 2.66 mg to 44.3 mg between days 49 and 105 and from 65.42 mg and 102.9 mg between days 147 and 252. The absolute numbers of adult Leydig cells per testis increased linearly from birth to 252 days. The average volume of adult Leydig cell on days 1, 7, 21 and 35 was not significantly different; a gradual and continued increase was observed thereafter, reaching a 3-fold increase at 196 and 252 days. Serum testosterone concentrations were not significantly different at day 1 compared days 7, 21, 35. Significant increases were observed at days 49 and 70. Values at days 70 and 105 and days 147, 196, and 252 were not significantly different. LH-stimulated testosterone production per testis in vitro was significantly different at day 1 compared days 7, 21, 35. Significant increases were observed at days 49 and 70. Hormonal values at days 105, 147, 196, and 252 were not significantly different. These data suggested Leydig cell developmental phase can be classified: a neonatal phase (1-7 days), a prepubertal phase (14-49 days) and an adult phase (70-252 days). Immature and mature adult Leydig cells, initially detected at days 7 and 49, respectively, and mature adult Leydig cells were abundant Leydig cell type according to the number and absolute volume per testis form day 49 onwards.

RG-II from Panax ginseng C.A. Meyer suppresses asthmatic reaction

  • Jung, In-Duk;Kim, Hye-Young;Park, Jin-Wook;Lee, Chang-Min;Noh, Kyung-Tae;Kang, Hyun-Kyu;Heo, Deok-Rim;Lee, Su-Jung;Son, Kwang-Hee;Park, Hee-Ju;Shin, Sung-Jae;Park, Jong-Hwan;Ryu, Seung-Wook;Park, Yeong-Min
    • BMB Reports
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    • v.45 no.2
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    • pp.79-84
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    • 2012
  • In asthma, T helper 2 (TH2)-type cytokines such as interleukin (IL)-4, IL-5, and IL-13 are produced by activated $CD^{4+}$ T cells. Dendritic cells played an important role in determining the fate of naive T cells into either $T_H1$ or $T_H2$ cells. We determined whether RG-II regulates the $T_H1/T_H2$ immune response by using an ovalbumin-induced murine model of asthma. RG-II reduced IL-4 production but increased interferon-gamma production, and inhibited GATA-3 gene expression. RG-II also inhibited asthmatic reactions including an increase in the number of eosinophils in bronchoalveolar lavage fluid, an increase in inflammatory cell infiltration in lung tissues, airway luminal narrowing, and airway hyperresponsiveness. This study provides evidence that RG-II plays a critical role in ameliorating the pathogenic process of asthmatic inflammation in mice. These findings provide new insights into the immunotherapeutic role of RG-II in terms of its effects in a murine model of asthma.

Environmental Fate and Effect of ZnO Nanoparticles (산화아연 나노입자의 환경 거동 및 영향 연구)

  • Ha, Ji Yeon;Jang, Min Hee;Hwang, Yu Sik
    • Journal of Korean Society of Environmental Engineers
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    • v.39 no.7
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    • pp.418-425
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    • 2017
  • ZnO nanoparticles (ZnO NPs) are mainly used in semiconductors, solar cells, biosensors, and cosmetics (sunscreen). In this study, we investigated the behavior of ZnO NPs in aquatic and soil environments and their effects on plants (Artemisia annua L.) in hydroponic cultivation. It was confirmed that the ZnO NPs size increased and their dissolution decreased with increasing in pH. Leaching distance of ZnO NPs was less than 2.5 cm, indicating that ZnO NPs had a little potential to leach into deeper soil layers. When ZnO NPs were exposed to plant, the total weights of plants decreased. The effects on the length of root and shoot were not observed. In addition large amount of ZnO NPs were adsorbed on the surface of plant root and didn't translocate into shoot. These results suggest that ZnO NPs block the pores of the root cell wall and decrease the bioavailability of plant nutrients. Therefore it can be speculated that the particles increase in size and settle down in the water environment and may adversely affect the plant growth by firmly adhering to the root surface when the ZnO NPs are exposed to the environment.

HMGB1 Switches Alkylating DNA Damage-Induced Apoptosis to Necrosis (HMGB1에 의한 alkylating DNA 손상에 의해 유도된 세포사멸의 세포괴사로의 전환)

  • Lee, Su-Yeon;Jeong, Eui-Kyong;Jeon, Hyun-Min;Ju, Min-Kyung;Kim, Cho-Hee;Park, Hye-Gyeong;Kang, Ho-Sung
    • Journal of Life Science
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    • v.21 no.7
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    • pp.953-960
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    • 2011
  • Necrosis is characterized by the cell membrane rupture and release of the cellular contents, including high-mobility group box 1 protein (HMGB1), into the extracellular microenvironment. HMGB1 acts as a transcriptional regulator in nuclei, but exerts a pro-inflammatory and tumor-promoting cytokine activity when released into the extracellular space. Its overexpression is associated with tumor progression and chemoresistance. Thus, HMGB1 acts as a clinically important molecule in tumor biology. In this study, we examined whether HMGB1 affects cell death induced by anti-cancer drugs. Here we show that HMGB1 prevented cisplatin (alkylating agent)-induced apoptosis and switched the cell fate to necrosis in MCF-7, MDA-MB231, and MDA-MB361 cells. Similar apoptosis-to-necrosis switch effects of HMGB1 were observed in cells treated with 4-HC, another alkylating agent. In contrast, HMGB1 did not exert any significant effects on docetaxel (DOC)-induced apoptosis in MCF-7 cells. We also show that cisplatin-induced apoptosis was switched to necrosis in MCF-7 multicellular tumor spheroids (MTS) that were cultured for 8 days and had necrotic cores, but DOC-induced apoptosis was prevented without the apoptosis-to-necrosis switch. Finally, the levels of RAGE, a receptor of HMGB1, were increased with extended culture of MTS. These findings demonstrate that HMGB1 switches alkylating agent-induced apoptosis to necrosis, suggesting that the strategy to prevent necrosis occurring as an undesirable action of alkylating agent-based chemotherapy should be delineated to improve the efficacy of chemotherapy for cancer.

Genetic Studies on the Sea Urchin Embryogenesis and Skeletogenesis (성게의 발생과 뼈대형성의 유전학적 연구)

  • Lee, Youn-Ho
    • The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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    • v.6 no.4
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    • pp.265-273
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    • 2001
  • The sea urchin has been used as sea food in many countries. This species has also been an important organism of embryological studies for more than a century. In recent years, sea urchin embryos are being used as testing materials for toxicity of pollutants and toxins. Usefulness of sea urchin embryos as experimental models comes from the easiness in obtaining sea urchin samples and a lot of gametes, in rearing embryos in the laboratory, in observing the cellular movement and organ formation during the embryogenesis and in manipulating blastomeres and genetic maferials. The sea urchin in itself is a key organism for the understanding of deuterostome evolution from the protostomes and of indirect development of marine invertebrates which undergo the planktotrophic larval stage. A fertilized sea urchin egg goes through rapid cleavage and becomes a 60 cell embryo 7hr after fertilization. It then develops into a morula, a blastula, a gastrula and finally a pluteus larva approximately 70 hr after fertilization. At the 60 cell stage, the embryo comprises of five territories that express territory-speciflc genes and later form different organs. Micromeres at the vegetal pole ingress into the blastoceol and become the primary mesenchyme cells(PMCs). PMCs express genes involved in skeletogenesis such as SM30, SM37, SM50, PM27, msp130. Among the genes, SM37 and SM50 are considered to be members of a gene family which is characterized by early blastula expression, Glycine-Proline-Glutamine rich repeat structures and spicule matrix forming basic proteins. Genetic studies on the sea urchin embryos help understand the molecular basis of indirect development of marine invertebrates and also of the biomineralization common to the animal kingdom.

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