• 제목/요약/키워드: Mitogenic effect

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The Effect of Fluoride and Aluminum on Bone Turnover in Mouse Calvarial Culture

  • Ahn, Hye-Won
    • Toxicological Research
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    • 제14권2호
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    • pp.163-169
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    • 1998
  • Fluoride (F), over a narrow concentration range, increases bone formation. Aluminum (Ai) too is biphasic in its action on bone, being mitogenic at very low levels and inhibitory at higher levels. Both F and Al are present in finished drinking water where the chemical interaction of these two agents is well characterized. F and AI, given individually, accumulate preferentially in bone. In addition. in vivo studies have shown that F causes the co-accumulation of Al in bone. Thus, it was necessary to determine the interactive effect of these two agents on bone mitogenesis. Calvaria were obtained from neonatal CD-1 mice and cultured with various concentrations of F (0.05~19 ppm) as NaF, Al (2 ppb~2 ppm) as $AlCl_3$ , or F and Al for 3 days at $37^{\circ}C$ on a rotating roller drum. Alkaline phosphatase activity in calvaria and $\beta$-glucuronidase activity in culture medium were determined as a measures of bone turnover. Alkaline phosphatase activity in calvaria was significantly increased by F (0.05~2 ppm) treatment and $\beta$-glucuronidase activity was slightly increased in the culture medium of calvaria treated with 0.3 ppm Al. The combination of 19 ppm F and 0.3 ppm Al increased alkaline phosphatase activity in calvaria, but did not affect $\beta$-glucuronidase activity, suggesting the interactive effect of fluoride and aluminum on bone turnover.

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Radioprotective effect of mefenamic acid against radiation-induced genotoxicity in human lymphocytes

  • Hosseinimehr, Seyed Jalal;Nobakht, Reyhaneh;Ghasemi, Arash;Pourfallah, Tayyeb Allahverdi
    • Radiation Oncology Journal
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    • 제33권3호
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    • pp.256-260
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    • 2015
  • Purpose: Mefenamic acid (MEF) as a non-steroidal anti-inflammatory drug is used as a medication for relieving of pain and inflammation. Radiation-induced inflammation process is involved in DNA damage and cell death. In this study, the radioprotective effect of MEF was investigated against genotoxicity induced by ionizing radiation in human blood lymphocytes. Materials and Methods: Peripheral blood samples were collected from human volunteers and incubated with MEF at different concentrations (5, 10, 50, or $100{\mu}M$) for two hours. The whole blood was exposed to ionizing radiation at a dose 1.5 Gy. Lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis blocked binucleated lymphocyte. Results: A significant decreasing in the frequency of micronuclei was observed in human lymphocytes irradiated with MEF as compared to irradiated lymphocytes without MEF. The maximum decreasing in frequency of micronuclei was observed at $100{\mu}M$ of MEF (38% decrease), providing maximal protection against ionizing radiation. Conclusion: The radioprotective effect of MEF is probably related to anti-inflammatory property of MEF on human lymphocytes.

Topical delivery of smad3 antisense using cationic solid lipid nanoparticle(SLN): therapeutic potential use and prevention of keloids

  • Jin, Su-Eon;Park, Jeong-Sook;Kim, Chong-Kook
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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    • pp.248.1-248.1
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    • 2003
  • Keloids are characterized by abnormal proliferation of fibroblasts and overproduction of collagen. Recently, it is reported that transforming growth factor beta (TGFb) and its signaling molecule, SMAD3 are related to the mitogenic effect of fibroblasts and a stimulatory factor for collagen synthesis. Cationic SLN was developed to improve the complex formation of DNA/SLN and enhance the uptake efficiency to cells. SLN was formulated by DC-Chol, DOPE, trimyristin as a solid core and other surfactant. The physical properties of the SLN and the ATS-SLN complex were characterized. (omitted)

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Lactobacillus rhamnosus GG의 면역조절작용과 장내 정착성 (Immunogenicity and Survival Strategy of Lactobacillus rhamnosus GG in the Human Gut)

  • 타다오 사이토;임광세
    • Journal of Dairy Science and Biotechnology
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    • 제30권1호
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    • pp.31-36
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    • 2012
  • Lactobacillus rhamnosus GG(ATCC 53103) is one of the best researched probiotic strains in the world. Studies in children have shown that Lactobacillus rhamnosus GG effectively prevents early atopic disease in patients with high risk. The active molecules associated with the immunostimulatory sequence and anti-allergy effects of L. rhamnosus GG have not yet been identified. Unmethylated CpG motifs in bacterial DNA have a mitogenic effect in mouse immune cells, CpG-containing ISS oligodeoxynucleotides are potent Th1 adjuvants, effective in both preventing and reversing Th2-biased immune deviation in allergy models. The genomic DNA of L. rhamnosus GG is a potent inducer of murine B cell and dendritic cell immunoactivation. In L. rhamnosus GG genomic DNA, ID35 shows high activity in ISS assays in both mice and humans. The effects of ID35 result from a unique TTTCGTT motif located at its 5'-end, and its effects are comparable with murine prototype CpG 1826. L. rhamnosus GG is known to secrete proteinaceous pili encoded by the spaCBA gene cluster. The presence of pili structures may be essential for its adhesion to human intestinal mucus, explaining the prolonged duration of intestinal residence of this bacterium, compared to that of non-piliated lactobacilli.

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오수유 열수추출액이 Cyclophosphamide 유도 면역억제에 미치는 효과 (Water Extracted Evodiae Fructus Possesses Immunomodulatory Activities on Cyclophosphamide Induced Immunesuppression)

  • 이영선;이금홍;박종현;권영규;신상우
    • 동의생리병리학회지
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    • 제21권6호
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    • pp.1450-1455
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    • 2007
  • Evodiae Fructus(EF) has been used as Traditional medicine for the treatment of headache, abdominal pain, hemorrhage, and menorrhae in many Asian countries. The present study was conducted to investigate the immunomodulatory effect on cyclophosphamide(CY)-induced immunesuppression of water extracted EF(EFE). In the mouse spleen cell proliferation assay, EFE enhanced mitogenic activity and restored the CY-induced cell suppression. In the nitric oxide(NO) assay, EFE inhibited NO production and iNOS protein levels in LPS-stimulated RAW 264.7 cells. In the GC-MS analysis, many ingredients of EFE were detected by solvents. These results indicated that EFE can modulate immune response through immune cell proliferation, the regulation of NO production and the inhibition of CY-induced immunotoxicity.

불화나트륨이 조골세포의 생리적 활성에 미치는 영향 (THE EFFECT OF SODIUM FLUORIDE ON THE PHYSIOLOGICAL ROLE OF OSTEOBLASTIC CELL)

  • 김대업
    • 대한소아치과학회지
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    • 제25권3호
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    • pp.635-648
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    • 1998
  • The clinical use of fluoride with a well known osteogenic action in osteoporotic patients is rational, because this condition is characterized by impaired bone formation. However, its anabolic effect has not been demonstrated well in vitro. The purpose of this study was to investigate the effects of sodium fluoride on the physiological role of osteoblastic cell. Osteoblastic cells were isolated from fetal rat calvaria. The results were as follows : 1. Mineralized nodules were shown in osteoblastic cell cultures, which had been maintained in the presence of ascorbic acid and ${\beta}-glycerophosphate$ up to 21 days. When cultures were treated with pulses of 48 hr duration before apparent mineralization was occurring, 2-fold increased in their number was detected. 2. Alkaline phosphatase activity of osteoblastic cells was inhibited by sodium fluoride in dose dependent manner. 3. The effect of sodium fluoride on the osteoblastic cell proliferation was measured by the incorporation of $[^3H]$-thymidine into DNA. As a result, sodium fluoride at $1{\sim}100{\mu}M$ increased the $[^3H]$-thymidine incorporation into DNA in a dose dependent manner. 4. The signaling mechanism activated by sodium fluoride dose-dependently enhanced the tyrosine phosphorylation of the adaptor molecule $Shc^{p66}$ and their association with Grb2, one of earlier events in a MAP kinase activation pathway cascade used by a significant subset of G protein-coupled receptors. 5. The phosphorylation of CREB(cAMP response element binding protein)was inhibited by the sodium fluoride in MC3T3E1 cells. In conclusion, the results of this study suggested that the mitogenic effect of the sodium fluoride in MC3T3E1 cell was stimulated in a dose-dependent manner and suggested "an important role for the interaction between She and Grb2" in controlling the proliferation of osteoblasts.

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Fumonisin B$_1$의 SD흰쥐에 대한 세포분열과 세포독성작용 (Mitogenic and Cytotoxic Effect of pure Fumonisin B$_1$, a carcinogen, in Sprague-Dawley Rats.)

  • Lim, Chae Woong;Has;Rim, Byung Moo
    • 한국환경성돌연변이발암원학회지
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    • 제16권1호
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    • pp.1-5
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    • 1996
  • Fumonisin B$_1$(FB$_1$)은 모든 동물종에서 간독성을 나타내며 흰쥐에서는 간암과 신장독성을 일으키는 발암물질이다. 본 연구에서는 FB$_1$의 반복투여 효과를 관찰하고자 수컷 Sprague-Dawley 흰쥐에 1 mg FB$_1$/kg을 1일(T$_1$) 혹은 2일(T$_2$), 3일(T$_3$)간 반복주사하였다. T$_1$군에서는 간장과 신장 다같이 독성작용이 발견되지 않았으나 간장에서는 대조군에 비해 5.5배의 증가된 세포분열상이 관찰되었다. 한편 T$_3$군에서는 병리조직학적 관찰과 혈청검사에서 간소엽 중심부에 병변이 있는 간독성이 관찰되었으며, 신장은 수질부 outer stripe에서 세포변성이 인정되었다. T$_3$군에서는 간효소를 포함하는 혈청검사치가 증가되었는데 특히 Cholesterol이 증가되었다. 따라서 FB$_1$의 반복 노출시에 신장보다는 간장에서 먼저 세포독성이 관찰되었으며 세포분열 역시 증가되었다.

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Induction of the Nuclear Proto-Oncogene c-fos by the Phorbol Ester TPA and c-H-Ras

  • Kazi, Julhash U.;Soh, Jae-Won
    • Molecules and Cells
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    • 제26권5호
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    • pp.462-467
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    • 2008
  • TPA is known to cooperate with an activated Ras oncogene in the transformation of rodent fibroblasts, but the biochemical mechanisms responsible for this effect have not been established. In the present study we used c-fos promoter-luciferase constructs as reporters, in transient transfection assays, in NIH3T3 cells to assess the mechanism of this cooperation. We found a marked synergistic interaction between TPA and a transfected v-Ha-ras oncogene in the activation of c-fos promoter and SRE. SRE has binding sites for TCF and SRF. A dominant-negative Ras (ras-N17) inhibited the TPA-Ras synergy by blocking the PKC-MAPK-TCF pathway. Dominant-negative RhoA and Rac1 (but not Cdc42Hs) inhibited the TPA-Ras synergy by blocking the Ras-Rho-SRF signaling pathway. Constitutively active $PKC{\alpha}$ and $PKC{\varepsilon}$ showed synergy with v-Ras. These results suggest that the activation of two distinct pathways such as Ras-Raf-ERK-TCF pathway and Rho-SRF pathway are responsible for the induction of c-fos by TPA and Ras in mitogenic signaling pathways.

Inhibitory Effect of Scutellaria barbata Don Water-extracts on Growth and DNA Incorporation of Human Cancer Cells

  • Kim, Dong-Il
    • 대한한의학회지
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    • 제27권4호
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    • pp.162-173
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    • 2006
  • The water-extracts of Scutellaria barbata Don (SBDE) were isolated from Chinese medicinal plant sources. The extracts showed strong growth-inhibitory activity and cancer chemopreventive activity on the growth and DNA incorporation of MG63 human osteosarcoma and K562 human leukemia cell lines. The growth of human cancer cells was inhibited in the presence of the extracts (20, 50 and 100 ${\mu}$g/ml), and the effects were concentration-dependent and incubation time-dependent up to 8 days. When 50 ${\mu}$g/ml of the extracts was added to the media of MG63 and K562, cell growth after 8 days or 6 days of incubation was retarded by 93.2 to 97.3% of the control group. Morphological changes of MG63 and K562 cell lines were observed. As the concentration of the extracts increased up to 50 ${\mu}$g/ml, degree of cell aggregation decreased. Moreover, the DNA incorporation of the cells which were labeled with [3H] thymidine was significantly reduced after 3 days of incubation at $37^{\circ}C$ with the extract. Therefore, it is suggested that the extract is highly effective on inhibition of cancer cell growth. The extract also inhibited gene expression of IGF-II in transcriptional level. Since IGF-II works as a mitogenic effector on MG63 and K562 cell lines, these results suggest that the growth inhibition is in part mediated through the inhibition of IGF-II gene expression.

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저출력레이저조사와 염증성 자극물질이 치은섬유아세포의 유전자 발현에 미치는 영향에 관한 실험적 연구 (An Experimental Study on the Effect of Low Level Laser and Some Cytokines on Gene Expression of Human Gingival Fibroblasts)

  • Jung-Min Kim;Keum-Back Shin
    • Journal of Oral Medicine and Pain
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    • 제19권2호
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    • pp.57-71
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    • 1994
  • Gingival fibroblasts were cultured and subjected to the test of Northern blot analysis for the demonstration of various mRNA expression in response to the low level laser treatment. For duplication of in vivo. Wound healing process, fibroblasts were pretreated with proinflammatory cytokine interleukin-1$\beta$(IL-1$\beta$) or mitogenic substance phorbol 12-myristate 13-acetate(PMA) prior to laser irradiation. The results were as follows : 1. By the laser irradiation, the gene expression of collagen type I was markedly increased I n gingival fibroblasts, especially in the case of PMA pretreatment. The gene expression of collagen type IV, however, was not only affected by laser irradiation but also by chemical cell stimulation. 2. Oncogene v-myc expression was affected by both laser irradiation and IL-1$\beta$ or PMA stimulation, But v-fos gene expression was not detected in any case of this experimental system. 3. Heat shock gene(Hsp 70)was expressed constiutively, but slightly increased by laser irradiation. 4. mRNA of fibroblast growth factor(FGF) was induced by both laser irradiation and IL-1$\beta$ or PMA treatment.

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