• Title/Summary/Keyword: Cellular System

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Comparing In Vitro and In Vivo Genomic Profiles Specific to Liver Toxicity Induced by Thioacetamide

  • Kang, Jin-Seok;Jeong, Youn-Kyoung;Shin, Ji-He;Suh, Soo-Kyung;Kim, Joo-Hwan;Lee, Eun-Mi;Kim, Seung-Hee;Park, Sue-Nie
    • Biomolecules & Therapeutics
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    • v.15 no.4
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    • pp.252-260
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    • 2007
  • As it is needed to assay possible feasibility of extrapolation between in vivo and in vitro systems and to develop a new in vitro method for toxicity testing, we investigated global gene expression from both animal and cell line treated with thioacetamide (TAA) and compared between in vivo and in vitro genomic profiles. For in vivo study, mice were orally treated with TAA and sacrificed at 6 and 24 h. For in vitro study, TAA was administered to a mouse hepatic cell line, BNL CL.2 and sampling was carried out at 6 and 24 h. Hepatotoxicity was assessed by analyzing hepatic enzymes and histopathological examination (in vivo) or lactate dehydrogenase (LDH) assay and morphological examination (in vitro). Global gene expression was assessed using microarray. In high dose TAA-treated group, there was centrilobular necrosis (in vivo) and cellular toxicity with an elevation of LDH (in vitro) at 24 h. Statistical analysis of global gene expression identified that there were similar numbers of altered genes found between in vivo and in vitro at each time points. Pathway analysis identified several common pathways existed between in vivo and in vitro system such as glutathione metabolism, bile acid biosynthesis, nitrogen metabolism, butanoate metabolism for hepatotoxicty caused by TAA. Our results suggest it may be feasible to develop toxicogenomics biomarkers by comparing in vivo and in vitro genomic profiles specific to TAA for application to prediction of liver toxicity.

Development of Multiclass Assignment For Dynamic Route Guidance Strategy (동적 경로안내전략수행을 위한 다계층 통행배정모형의 개발)

  • Lee, Jun;Lim, Kang-Won;Lee, Young-Ihn;Lim, Yong-Taek
    • Journal of Korean Society of Transportation
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    • v.22 no.7 s.78
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    • pp.91-98
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    • 2004
  • This study focuses on the development of dynamic assignment for evaluation and application for dynamic route guidance strategy. Travelers are classified according to information contents which they received pre/on trip. The first group have no traffic information, so they travel with fixed route. The second group have real-time shortest path and travel according to it. The last group have car navigation system or individual method(cellular phone, PDA-two way communication available) for traffic information on trip. And then they are assigned in accordance with the proposed multiclass dynamic assignment model. At this time the last group is gotten under control with DFS(decentralized feedback strategy). In use of this Process we expect that various traffic information strategy can be tested and also be the key factor for success of ITS, location of VMS(variable message sign), cycle of information, area of traffic information, etc).

Human Lung Insults due Air Pollutant -A Review for Priority Setting in the Research- (대기오염에 의한 폐장조직 손상 -연구방향의 설정을 위한 논의-)

  • 김건열;백도명
    • Journal of environmental and Sanitary engineering
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    • v.7 no.2
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    • pp.95-110
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    • 1992
  • Much progress has been made in understanding the subcellular events of the human lung injuries after acute exposure to environmental air pollutants. Host of those events represent oxidative damages mediated by reactive oxygen species such as superoxide, hydrogen peroxide, and the hydroxy, free radical. Recently, nitric oxide (NO) was found to be endogenously produced by endothelial cells and cells of the reticulo-endothelial system as endothelialderived relaxation factor (EDRF) which is a vasoactive and neurotransmitter substance. Together with superoxide, NO can form another strong oxidant, peroxonitrite. The relative importance of exogenous sources of $N0/N0_2$ and endogenous production of NO by the EDRF producing enzymes in the oxidative stresses to the heman lung has to be elucidated. The exact events leading to chronic irreversible damage are still yet to be known. From chronic exposure to oxidant gases, progressive epithelial and interstitial damages develop. Type I epithelial cells become thicker and cover a smaller average alveolar surface area while thee II cells proliferate instead. Under acute damages, the extent of loss of the alveolar epithelial cell lining, especially type II cells appears to be a good predictor of the ensuing irreversible damage to alveolar compartment. Interstitial matrix undergo remodeling during chronic exposure with increased collagen fibers and interstitial fibroblasts. However, Inany of these changes can be reversed after cessation of exposure. Among chronic lung injuries, genetic damages and repair responses received particular attention in view of the known increased lung cancer risks from exposure to several air pollutants. Heavy metals from foundry emission, automobile traffics, and total suspended particulate, especially polycystic aromatic hydrocarbons have been positively linked with the development of lung cancer. Asbestos in another air pollutant with known risk of lung cancer and mesothelioma, but asbestos fibers are nonauthentic in most bioassays. Studies using the electron spin resonance spin trapping method show that the presence of iron in asbestos accelerates the production of the hydroxy, radical in vitro. Interactions of these reactive oxygen species with particular cellular components and disruption of cell defense mechanisms still await further studies to elucidate the carcinogenic potential of asbestos fibers of different size and chemical composition. The distribution of inhaled pollutants and the magnitude of their eventual effects on the respiratory tract are determined by pollutant-independent physical factors such as anatomy of the respiratory tract and level and pattern of breathing, as well as by pollutant-specific phyco-chemical factors such as the reactivity, solubility, and diffusivity of the foreign gas in mucus, blood and tissue. Many of these individual factors determining dose can be quantified in vitro. However, mathematical models based on these factors should be validated for its integrity by using data from intact human lungs.

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Luteolin-loaded Phytosomes Sensitize Human Breast Carcinoma MDA-MB 231 Cells to Doxorubicin by Suppressing Nrf2 Mediated Signalling

  • Sabzichi, Mehdi;Hamishehkar, Hamed;Ramezani, Fatemeh;Sharifi, Simin;Tabasinezhad, Maryam;Pirouzpanah, Mohammadbagher;Ghanbari, Parisa;Samadi, Nasser
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5311-5316
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    • 2014
  • Nuclear factor erythroid 2-related factor 2 (Nrf2) has been recognized as a transcription factor that controls mechanisms of cellular defense response by regulation of three classes of genes, including endogenous antioxidants, phase II detoxifying enzymes and transporters. Previous studies have revealed roles of Nrf2 in resistance to chemotherapeutic agents and high level expression of Nrf2 has been found in many types of cancer. At physiological concentrations, luteolin as a flavonoid compound can inhibit Nrf2 and sensitize cancer cells to chemotherapeutic agents. We reported luteolin loaded in phytosomes as an advanced nanoparticle carrier sensitized MDA-MB 231 cells to doxorubicin. In this study, we prepared nano phytosomes of luteolin to enhance the bioavailability of luteolin and improve passive targeting in breast cancer cells. Our results showed that cotreatment of cells with nano particles containing luteolin and doxorubicin resulted in the highest percentage cell death in MDA-MB 231cells (p<0.05). Furthermore, luteolin-loaded nanoparticles reduced Nrf2 gene expression at the mRNA level in cells to a greater extent than luteolin alone (p<0.05). Similarly, expression of downstream genes for Nrf2 including Ho1 and MDR1 were reduced significantly (p<0.05). Inhibition of Nrf-2 expression caused a marked increase in cancer cell death (p<0.05). Taken together, these results suggest that phytosome technology can improve the efficacy of chemotherapy by overcoming resistance and enhancing permeability of cancer cells to chemical agents and may thus be considered as a potential delivery system to improve therapeutic protocols for cancer patients.

Deoxynivalenol- and zearalenone-contaminated feeds alter gene expression profiles in the livers of piglets

  • Reddy, Kondreddy Eswar;Jeong, Jin young;Lee, Yookyung;Lee, Hyun-Jeong;Kim, Min Seok;Kim, Dong-Wook;Jung, Hyun Jung;Choe, Changyong;Oh, Young Kyoon;Lee, Sung Dae
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.4
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    • pp.595-606
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    • 2018
  • Objective: The Fusarium mycotoxins of deoxynivalenol (DON) and zerolenone (ZEN) cause health hazards for both humans and farm animals. Therefore, the main intention of this study was to reveal DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the liver of piglets. Methods: In the present study, 15 six-week-old piglets were randomly assigned to the following three different dietary treatments for 4 weeks: control diet, diet containing 8 mg DON/kg feed, and diet containing 0.8 mg ZEN/kg feed. After 4 weeks, liver samples were collected and sequenced using RNA-Seq to investigate the effects of the mycotoxins on genes and gene networks associated with the immune systems of the piglets. Results: Our analysis identified a total of 249 differentially expressed genes (DEGs), which included 99 upregulated and 150 downregulated genes in both the DON and ZEN dietary treatment groups. After biological pathway analysis, the DEGs were determined to be significantly enriched in gene ontology terms associated with many biological pathways, including immune response and cellular and metabolic processes. Consistent with inflammatory stimulation due to the mycotoxin-contaminated diet, the following Kyoto encyclopedia of genes and genomes pathways, which were related to disease and immune responses, were found to be enriched in the DEGs: allograft rejection pathway, cell adhesion molecules, graft-versus-host disease, autoimmune thyroid disease (AITD), type I diabetes mellitus, human T-cell leukemia lymphoma virus infection, and viral carcinogenesis. Genome-wide expression analysis revealed that DON and ZEN treatments downregulated the expression of the majority of the DEGs that were associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9), proliferation (insulin-like growth factor 1, major facilitator superfamily domain containing 2A, insulin-like growth factor binding protein 2, lipase G, and salt inducible kinase 1), and other immune response networks (paired immunoglobulin-like type 2 receptor beta, Src-like-adaptor-1 [SLA1], SLA3, SLA5, SLA7, claudin 4, nicotinamide N-methyltransferase, thyrotropin-releasing hormone degrading enzyme, ubiquitin D, histone $H_2B$ type 1, and serum amyloid A). Conclusion: In summary, our results demonstrated that high concentrations DON and ZEN disrupt immune-related processes in the liver.

Effects of deoxynivalenol- and zearalenone-contaminated feed on the gene expression profiles in the kidneys of piglets

  • Reddy, Kondreddy Eswar;Lee, Woong;Jeong, Jin young;Lee, Yookyung;Lee, Hyun-Jeong;Kim, Min Seok;Kim, Dong-Woon;Yu, Dongjo;Cho, Ara;Oh, Young Kyoon;Lee, Sung Dae
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.1
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    • pp.138-148
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    • 2018
  • Objective: Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN), common contaminants in the feed of farm animals, cause immune function impairment and organ inflammation. Consequently, the main objective of this study was to elucidate DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the kidneys of piglets. Methods: Fifteen 6-week-old piglets were randomly assigned to three dietary treatments for 4 weeks: control diet, and diets contaminated with either 8 mg DON/kg feed or 0.8 mg ZEN/kg feed. Kidney samples were collected after treatment, and RNA-seq was used to investigate the effects on immune-related genes and gene networks. Results: A total of 186 differentially expressed genes (DEGs) were screened (120 upregulated and 66 downregulated). Gene ontology analysis revealed that the immune response, and cellular and metabolic processes were significantly controlled by these DEGs. The inflammatory stimulation might be an effect of the following enriched Kyoto encyclopedia of genes and genomes pathway analysis found related to immune and disease responses: cytokine-cytokine receptor interaction, chemokine signaling pathway, toll-like receptor signaling pathway, systemic lupus erythematosus (SLE), tuberculosis, Epstein-Barr virus infection, and chemical carcinogenesis. The effects of DON and ZEN on genome-wide expression were assessed, and it was found that the DEGs associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9, CXCL10, chemokine [C-C motif] ligand 4), proliferation (insulin like growth factor binding protein 4, IgG heavy chain, receptor-type tyrosine-protein phosphatase C, cytochrome P450 1A1, ATP-binding cassette sub-family 8), and other immune response networks (lysozyme, complement component 4 binding protein alpha, oligoadenylate synthetase 2, signaling lymphocytic activation molecule-9, ${\alpha}$-aminoadipic semialdehyde dehydrogenase, Ig lambda chain c region, pyruvate dehydrogenase kinase, isozyme 4, carboxylesterase 1), were suppressed by DON and ZEN. Conclusion: In summary, our results indicate that high concentrations of DON and ZEN suppress the inflammatory response in kidneys, leading to potential effects on immune homeostasis.

On the Optimal Selection of Wireless Access in Interoperating Heterogeneous Wireless Networks (3G/WLAN/휴대인터넷 연동상황을 고려한 사용자의 최적 무선접속서비스 선택방법에 대한 연구)

  • Cho Geun-Ho;Choe Jin-Woo;Jun Sung-Ik;Kim Young-Sae
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.31 no.5B
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    • pp.456-477
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    • 2006
  • Due to advances in wireless communication technology and increasing demand for various types of wireless access, cellular, WLAN, and portable internet(such as WiBro and IEEE 802.16) systems are likely to be integrated into a unified wireless access system. This expectation premises the availability of multi-mode handsets and cooperative interworking of heterogenous wireless access networks allied by roaming contracts. Under such environments, a user may lie in the situation where more than one wireless accesses are available at his/her location, and he/she will want to choose the 'best' access among them. In this paper, we define the 'best' access(es) as the access(es) that charges minimum cost while fulfilling the required QoS of wireless access, and address the problem of choosing the optimal set of accesses theoretically by introducing a graph representation of service environment. Two optimal selection algorithms are proposed, which individually consider cases where single or multiple wireless access can be supported by multi-mode handsets.

Endothelin-l as a Regulator of Vascular Smooth Muscle Contraction-related Signal Transduction and Endothelin-l-induced Pain-related Nociception -The Approach of Basic Physical Therapy for the Study of Pain Specialized Physical Therapy- (혈관평활근 수축-연관 신호전달 체계에 대한 Endothelin-1의 역할과 Endothelin-1-유도통증-연관 유해감각 -통증전문물리치료 연구를 위한 기초물리치료학적 접근을 중심으로-)

  • Kim, Jung-Hwan;Lee, Sook-Hee;Lee, Sang-Bin;Choi, Yoo-Rim;Kim, Bo-Kyung;Park, Ju-Hyun;Koo, Ja-Pung;Choi, Wan-Suk;An, Ho-Jung;Choi, Jeong-Hyun;Kim, Moo-Gi;Kim, Soon-Hee
    • Journal of Korean Physical Therapy Science
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    • v.13 no.2
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    • pp.99-119
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    • 2006
  • Endothelin (ET) is a 21 amino acid peptide with multifunctional effects on the vasculature as well as a variety of other cell types such as respiratory, gastrointestinal, urogenital, endocrine, central nervous systems, and others. Endothelin has emerged as a modulator by autocrine and paracrine actions for many cellular activities, including vasoconstriction, cell proliferation, hormone production, neurotransmitter and/or neuromodulator. The endothelin family consists of three closely related peptides, ET-1, ET-2, and ET-3 derived from separate genes, such as chromosome 6, 1, and 20, respectively. ET-1 is the predominant isoform produced in the cardiovascular system and about which most is known. Endothelin receptors are seven-transmembrane GTP-binding protein-coupled receptors, which are classified into endothelin-A (ETA) and endothelin-B (ETB) receptors. Interestingly, recent evidence is accumulating to suggest that ET -1 may contribute to a variety of pain states such as allodynia and hyperalgesia in animals and humans. Therefore, in this review the biological characteristics and contraction-related mechanism of endothelin-1 in mammalian cells will be summarized. Especially, we focus on multifunctional roles for ET-1 in noxious stimulation-induced pain for the study of pain specialized physical therapy.

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Induction of Fas-Mediated Apoptosis by Interferon-g is Dependent on Granulosa Cell Differentiation and Follicular Maturation in the Rat Ovary

  • Lee, Hye-Jeong;Kim, Ji Young;Park, Ji Eun;Yoon, Yong-Dal;Tsang, Benjamin K.;Kim, Jong-Min
    • Development and Reproduction
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    • v.20 no.4
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    • pp.315-329
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    • 2016
  • Fas ligand (FasL) and its receptor Fas have been implicated in granulosa cell apoptosis during follicular atresia. Although interferon-gamma (IFN-${\gamma}$) is believed to be involved in the regulation Fas expression in differentiated granulosa or granulosa-luteal cells, the expression of this cytokine and its role in the regulation of the granulosa cell Fas/FasL system and apoptosis during follicular maturation have not been thoroughly investigated. In the present study, we have examined the presence of IFN-${\gamma}$ in ovarian follicles at different stage of development by immunohistochemistry and related their relative intensities with follicular expression of Fas and FasL, and with differences in granulosa cell sensitivity to Fas activation by exogenous agonistic Anti-Fas monoclonal antibody (Fas mAb). Although IFN-${\gamma}$ immunostaining was detectable in oocyte and granulosa cells in antral follicles, most intense immunoreactivity for the cytokine was observed in these cells of preantral follicles. Intense immunoreactivity for IFN-${\gamma}$ was most evident in granulosa cells of atretic early antral follicles where increased Fas and FasL expression and apoptosis were also observed. Whereas low concentrations of IFN-${\gamma}$ (10-100 U/mL) significantly increased Fas expression in undifferentiated granulosa cells (from preantral or very early antral follicles) in vitro, very higher concentrations (${\geq}1,000U/mL$) were required to up-regulate of Fas in differentiated cells isolated from eCG-primed (antral) follicles. Addition of agonistic Fas mAb to cultures of granulosa cells at the two stages of differentiation and pretreated with IFN-${\gamma}$ (100 U/mL) elicited morphological and biochemical apoptotic features which were more prominent in cells not previously exposed to the gonadotropin in vivo. These findings suggested that IFN-${\gamma}$ is an important physiologic intra-ovarian regulator of follicular atresia and plays a pivotal role in regulation of expression of Fas receptor and subsequent apoptotic response in undifferentiated (or poorly differentiated) granulosa cells at an early (penultimate) stage of follicular development.

Modified Kranz Structure in Leaves of Salsola collina (Salsola collina 엽육조직내 변형된 크란츠구조)

  • Kim, In-Sun
    • Applied Microscopy
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    • v.31 no.2
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    • pp.207-214
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    • 2001
  • Anatomy and ultrastructure of the modifeid Krana pattern have been studied in succulent Salsola collina Pall. Cylindrical leaves exhibited the Salsoloid Kranz type containing two layers of peripheral chlorenchyma that surrounded the water storage cells and vascular tissues. Small veins were also peripherally arranged, but mostly embedded in the vicinity of the inner chlorenchma without the orderly arrangement of the concentric layering of bundle sheath and mesophyll cells. The current study mainly focused on the chlorenchyma tissue abutting such minor veins. The outer columnar layer exhibited features similar to the characteristics of palisade mesophyll cells, while the inner cuboid layer to the bundle sheath cells of a typical $C_4$ Kranz pattern. Cellular components of the inner chlorenchyma were centripetal and numerous, but starch-laden chloroplasts were rudimentary in the thylakoidal system. The outer chlorenchyma demonstrated normally developed chloroplasts having well-stacked thylakoids and plastoglobuli. Branched and complicated plasmodesmata frequently occurred in thick interfaces of the two layers, implying the active movement of the photosynthates between them. The present data were mostly congruent with one of the structural features of the C4 subtypes , NADP-ME type, reported in the $C_4$ pattern. The Kranz pattern encountered in this Salsola probably has been directly related to the structural modification that occurred during a functional adaptation to the $C_4$ photosynthesis.

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