• 제목/요약/키워드: normal rodent

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Recent Advances in Cellular Senescence, Cancer and Aging

  • Lim, Chang-Su;Judith Campisi
    • Biotechnology and Bioprocess Engineering:BBE
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    • 제6권4호
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    • pp.231-236
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    • 2001
  • How much do we know about the biology of aging from cell culture studies Most normal somatic cells have a finite potential to divide due to a process termed cellular or replicative senescence. A growing body evidence suggests that senescence evolved to protect higher eu-karyotes, particularly mammals, from developing cancer, We now know that telomere shortening due to the biochemistry of DNA replication, induces replicative senescence in human cells. How-ever in rodent cells, replicative senescence occurs despite very long telomeres. Recent findings suggest that replicative senescence is just the tip of the iceberg of a more general process termed cellular senescence. It appears that cellular senescence is a response to potentially oncogenic in-sults, including oxidative damage. In young orgainsms, growth arrest by cell senescence sup-presses tumor development, but later in life, due to the accumulation of senescent cells which se-cret factors that can disrupt tissues during aging, cellular senescence promotes tumorigenesis. Therefore, antagonistic pleiotropy may explain, if not in whole the apparently paradoxical effects of cellular senescence, though this still remains an open question.

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CTLA-4-Tg/CD-28-KO Mice Exhibit Reduced T Cell Proliferation in vivo Compared to CD-28-KO Mice in a Graft-versus-host Disease Model

  • Yoo, Jong-Sun;Lee, Yun-Jung;Yoon, Joo-Won;Hyung, Kyeong-Eun;Hwang, Kwang-Woo
    • The Korean Journal of Physiology and Pharmacology
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    • 제16권5호
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    • pp.349-353
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    • 2012
  • Activated T cells express inhibitory receptors such as CTLA-4 that can downregulate immune responses. Blockade of or genetic deficiency in CTLA-4 can result in autoimmunity. Therefore, strategies to increase the inhibitory function of CTLA-4 may be attractive in settings of undesirable T cell responses such as autoimmunity or transplant rejection. We have tested the hypothesis that transgenic constitutive expression of CTLA-4 can further attenuate immune responses when compared with normal inducible expression. Our results indicate that transgenic expression of CTLA-4 in mouse T cells (CTLA-4-Tg T cells) results in reduced cell cycle progression and increased apoptosis of TCR-stimulated T cells. CTLA-4-Tg T cells display reduced T cell proliferation in an in vivo model of graft versus host disease (GVHD). These results further our understanding of how CTLA-4 can be manipulated to inhibit immune responses and may help development of new therapeutic strategies for clinical settings of autoimmunity and transplantation.

Generation of Transgenic Mice with Overexpression of Mouse Resistin

  • Lee, H. T.;J. R. Chun.;K. S. Chung
    • Korean Journal of Animal Reproduction
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    • 제26권4호
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    • pp.321-328
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    • 2002
  • The hormone resistin is associated with type II diabetes mellitus in rodent model. Resistin impairs glucose tolerance and insulin action. A new class of anti-diabetic drugs were called thiazolidinediones (TZDs) downreguates a resistin. Resistin gene expression is induced during adipocyte differentiation and resistin polypeptide is secreted by adipocytes. But, the correlation between increased adiposity and resistin remains unknown. The objectives of this study was to clone a mouse resistin CDNA and to generate transgenic mice overexpressing mouse resistin gene. The pCMV-mus/resistin gene was prepared from previous recombinant pTargeT$^{TM}$-mus/resistin by digestion of Bgl II, and has used for microin- jection into pronuclei of one cell embryos. Mouse resistin expression was detected in transgenic F$_1$mice by RT-PCR. The transgenic mouse with resistin gene expression has heavier body weight which was measured higher level of plasma glucose than that of normal mouse. And in diet-induced experiments, in fasting group, resistin expression was higher than that of re-feeding group. This result demonstrates that the resistin gene overexpressing mice may be became to obesity and be useful as an animal disease model to be diabetes caused by insulin resistance of resistin.n.

Measurement and Analysis of Rodent Biological Signals using Telemetry System (원격측정장치를 이용한 설치류의 생체신호 측정 및 분석)

  • Kim, Chang-Hwan;Hur, Gyeong-Haeng
    • Journal of the Korea Institute of Military Science and Technology
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    • 제14권6호
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    • pp.1159-1165
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    • 2011
  • Telemetry techniques of rats have been used for assessing safety pharmacology of drugs and chemicals. Biological signals including blood pressure and heart rate measured under anesthesia were significantly different from those obtained under normal conditions. The stress of restraint in awake animals can also affect the accuracy of physiological evaluation. This paper details the surgery required to allow key cardiovascular parameters to be determined. The telemetric measurement of cardiovascular parameters such as blood pressure, heart rate, electrocardiograph(ECG) established. We carried out the continuous monitoring of cardiovascular parameters using the telemetry system in F344 rats. During the measurement, no significant changes were observed in the heart rate and blood pressure. ECG signals and body temperature were also constant during the measurement of biological signals. With the results of this study, we conclude that this telemetry system can be applied usefully for the assesment of biological parameters in the rats.

Effects of Tong Xin Lou (TXL) on levels of serum lipid in high fat diet-induced dyslipidemia in mice (통심락(通心絡)이 고지방식이로 유도된 이상지질혈증 생쥐의 체내 지질 변화에 미치는 영향)

  • Ha, Tae-Hoon;Kim, Hyun-Young;Kim, Hyung-Woo;Cho, Su-In;Kim, Young-Gyun
    • The Korea Journal of Herbology
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    • 제27권3호
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    • pp.107-112
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    • 2012
  • Objectives : This study was designed to investigate the effects of Tong Xin Lou (TXL) on lipid accumulation in liver tissue in Hypercholesterolemic mice. TXL is new drug, which is one of Cardiotonic Pills. TXL is used for activating the blood flow in the restoration stage of cerebral infarction, and for alleviation of angina pectoris including the symptoms as chest oppressed and stabbing pain. Methods : Hyperlipidemia was induced by providing high fat diet for 6 weeks. Normal group was provided with normal rodent diet. TXL was administered orally in the concentration of 10 mg/day for 2 weeks (TXL group). D/W was administered orally in CTL group for 2 weeks. We observed histopathological changes in liver and heart tissues, and also investigated the effect on body weights, and levels of total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride in serum. Results : In this study, TXL did not affects weight gain in hypercholesterolemic mice. TXL group showed downward tendency of lipid accumulation compared with CTL group. In addition, oral administration of TXL lowered levels of total cholesterol (P < 0.05) and triglyceride (P < 0.05), which were elevated by induction of hypercholesterolemia. Conclusion : These results suggest that TXL can prevent lipid accumulation in liver tissue through regulation of dyslipidemia.

HD047703, a New Promising Anti-Diabetic Drug Candidate: In Vivo Preclinical Studies

  • Kim, SoRa;Kim, Dae Hoon;Kim, Young-Seok;Ha, Tae-Young;Yang, Jin;Park, Soo Hyun;Jeong, Kwang Won;Rhee, Jae-Keol
    • Biomolecules & Therapeutics
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    • 제22권5호
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    • pp.400-405
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    • 2014
  • G-protein coupled receptor 119 (GPR119) has emerged as a novel target for the treatment of type 2 diabetes mellitus. GPR119 is involved in glucose-stimulated insulin secretion (GSIS) from the pancreatic b-cells and intestinal cells. In this study, we identified a novel small-molecule GPR119 agonist, HD047703, which raises intracellular cAMP concentrations in pancreatic ${\beta}$-cells and can be expected to potentiate glucose-stimulated insulin secretion from human GPR119 receptor stably expressing cells (CHO cells). We evaluated the acute efficacy of HD047703 by the oral glucose tolerance test (OGTT) in normal C57BL/6J mice. Then, chronic administrations of HD047703 were performed to determine its efficacy in various diabetic rodent models. Single administration of HD047703 caused improved glycemic control during OGTT in a dose-dependent manner in normal mice, and the plasma GLP-1 level was also increased. With respect to chronic efficacy, we observed a decline in blood glucose levels in db/db, ob/ob and DIO mice. These results suggest that HD047703 may be a potentially promising anti-diabetic agent.

Reproductive Aging in Female Rodents (암컷 설치류에서의 생식 노화)

  • Lee, Sung-Ho
    • Development and Reproduction
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    • 제11권1호
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    • pp.13-20
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    • 2007
  • In all female mammals, reproductive system is one of the first biological systems to show age-related decline. Female mammals in reproductive aging, though the phenomena is somewhat species-specific, start to show declining fertility and changes of numerous physiological functions. This review will present a current information on the aging of the female reproductive hormonal axis and introduce three useful rodent models for studying this field. Middle age($8{\sim}12$ months old) in female rats and mice is comparable to the stage prior to the entry of menopause in human. In this period pulsatile and surge GnRH secretion from hypothalamus gradually attenuated, then reduced pulsatile and surge LH secretion is followed consequently. This age-related defects in GnRH-LH neuroendocrine axis seem to be highly correlated with the defects in brain signals which modulate the activities of GnRH neuron. Many researchers support the idea which the age-related hypothalamic defects are the main cause of reproductive aging, but some ovarian factors such as inhibin response also could contribute to the induction of reproductive senescence. Some rodent models are quite valuable in studying the reproductive aging. The follitropin receptor knockout(FORKO) mice, both of null and haploinsufficient state, could produce depletion of oocyte/follicle with age. Dioxin/aryl hydrocarbon receptor(AhR) knockout mice also show severe ovarian defects and poor reproductive success early in their life compared to the age-matched normal mice. Further studies on the reproductive aging will be a great help to evaluate the benefits and risks of hormone replacement therapy(HRT) and to improve the safety of HRT.

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Biological Effects of C. tricuspidata Extract in Normal Rodents (꾸지뽕 추출물의 생리활성 연구)

  • Mi Sun Hwang;Ji Yeon Choi;Kang Min Kim;Il Dae Song
    • Journal of Life Science
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    • 제33권4호
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    • pp.363-370
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    • 2023
  • In order to use Cudrania tricuspidata extract for the development of health-functional food, biological changes in normal rodents, such as changes in blood constituent cells, blood lipids, and anti-inflammatory activity, were measured after the rodents had been drinking the substance for 2 weeks. A 30 mg daily dose of the extract taken for 2 weeks produced no change in body weight or renal function, and no toxicity was observed. Increased red blood cell levels and white blood cell levels were confirmed, and platelet counts tended to increase; thus, the extract seems to cause an overall increase in blood cells. In the case of blood lipids, it was confirmed that the extract-treated group exhibited an effect of improved blood-lipid levels, demonstrated through an increase in HDL-C of 21%, with a decrease in triglyceride of 27% compared to the control group. In addition, the decreases in both GOT and GPT led to improved liver function through use of the extract. Therefore, this study suggests that drinking Cudrania tricuspidata extract can have various effects, such as promoting blood cell production, improving blood lipids profile, improving liver function, and improving inflammatory action. The extract would be useful in the future in developing high-value industrial products such as functional foods and pharmaceuticals.

Characteristics of Antidiabetic Effect of Dioscorea rhizoma(2) - Prevention of Diabetic Neuropathy by NGF Induction - (산약의 항당뇨 특성 연구(2) - NGF 유도 신경병증예방 -)

  • Kang, Tong-Ho;Choi, Sang-Zin;Lee, Tae-Ho;Son, Mi-Won;Park, Ji-Ho;Kim, Sun-Yeou
    • The Korean Journal of Food And Nutrition
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    • 제21권4호
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    • pp.430-435
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    • 2008
  • The main cause of diabetic neuropathy, one of the most debilitating complications, is the chronic hyperglycemia, the increase sorbitol or the decrease of nerve growth factor(NGF). NGF, a protein, plays a major role in the development and maintenance of peripheral nervous system. Systemic administration of NGF prevents manifestations of neuropathy in rodent models of diabetic neuropathy. In the previous investigation, we report the hypoglycemia effect of Dioscorea rhizoma extract(DRE) in diabetic mice. The present study shows protective effect of DRE on diabetic neuropathy by induction of NGF protein. We investigated the NGF level in salivary gland and sciatic nerve of normal mouse and the effect of DRE on sciatic nerve conductivity and thermal hyperalgesia test in Type 2 db/db mouse. DRE increased endogenous NGF level in salivary gland and sciatic nerve of mouse. And sensory nerve conductivity velocity(SNCV), motor nerve conductivity velocity(MNCV) and thermal hyperalgesia increased in DRE treatment mice compared with control group. On the basis of our results, we conclude that DRE increase induction of endogenous NGF level and have protective effect on diabetic neuropathy by induction of NGF. Therefore, we propose that long-term use of DRE might help prevention of diabetes-associated complication; diabetic neuropathy.

Rodent model for long-term maintenance and development of the viable cysticerci of Taenia saginata asiatica

  • Wang, I.C.;Chung, W.C.;Lu, S.C.;Fan, P.C.
    • Parasites, Hosts and Diseases
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    • 제38권4호
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    • pp.237-244
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    • 2000
  • Although oncospheres of Taenia saginata asiatica can develop into cysticerci in immunodeficiency, immunosuppressed, and normal mice, no detailed information on the development features of these cysticerci from SCID mice is available. In the present study, the tumor-like cyst was found in the subcutaneous tissues of each of 10 SCID mice after 38-244 days inoculation with 39,000 oncospheres of T. s. asiatica. These cysts weighed 2.0-9.6 gm and were 1.5-4.3 cm in diameter. The number of cysticerci were collected from these cysts ranged from 125 to 1,794 and the cysticercus recovery rate from 0.3% to 4.6%. All cysticerci were viable with a diameter of 1-6 mm and 9 abnormal ones each with 2 evaginated protoscoleces were also found. The mean length and width of scolex, protoscolex, and bladder were $477{\;}{\times}{\;}558,{\;}756{\;}{\times}{\;}727,{\;}and{\;}1,586{\;}{\times}{\;}1,615{\;}$\mu\textrm{m}$, respectively. The diameters of suckers and rostellum were $220{\mu\textrm{m}}{\;}and{\;}70\mu\textrm{m}$, respectively All cysticerci had two rows of rostellar hooks. These findings suggest that the SCID mouse model can be employed as a tool for long-term maintenance of the biological materials for advanced studies of immunodiagnosis, vaccine development, and evaluation of cestocidal drugs which would be most benefit for the good health of the livestocks.

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