• Title/Summary/Keyword: p53 activation

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Cerebellar Activation Related to Various Tasks Using fMRI (다양한 임무 부여시 기능적 자기공명영상에서 관찰된 소뇌의 활성화)

  • Hwang, Seung-Bae;Kwak, Hyo-Sung;Lee, Sang-Yong;Jin, Gong-Yong;Han, Young-Min;Kim, Young-Kon;Chung, Gyung-Ho
    • Investigative Magnetic Resonance Imaging
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    • v.13 no.1
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    • pp.47-53
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    • 2009
  • Purpose : Although it's been known for half a century that unique structures have evolved in the cerebellum and they then became greatly enlarged in the human brain, the function of these structures still remains unknown. The purpose of this study was to assess cerebellar activation during motor, sensory, word generation, listening comprehension, and working memory tasks with using functional magnetic resonance imaging (fMRI). Materials and Methods : Eleven healthy right-handed subjects (Male: female, 6:5, mean age: 27.4years) were imaged on a Siemens 1.5T scanner. Whole brain functional maps were acquired using BOLD EPI sequences in the axial plane. Each paradigm consisted of five epochs of activation vs. the control condition. The activation tasks consisted of left finger complex movement, sensory stimulation of the left hand, word generation, listening comprehension, and working memory tasks. The reference function was a boxcar waveform. The activation maps were thresholded at p = 0.001. SPM 5 evaluated the activated areas and responses within the cerebellum. Results : Cerebellar activation was observed on motor task, word generation task, and working memory task. There were 949 activated areas and the mean fitted and adjusted response was 0.68 during the motor task. There were 319 activated areas and the mean fitted and adjusted response was 0.15 during the word generation task. There were 330 activated areas and the mean fitted and adjusted response was 0.26 during the working memory task. Conclusion : Our results suggest that the cerebellum is involved in a variety of functional tasks, including motor, word generation, and working memory tasks. However, during the motor task, the cerebellum showed a large activated area and a high response. Cerebellar function can be evaluated by fMRI.

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Ethanolic Extract of Marsdenia condurango Ameliorates Benzo[a]pyrene-induced Lung Cancer of Rats -Condurango Ameliorates BaP-induced Lung Cancer in Rats-

  • Sikdar, Sourav;Mukherjee, Avinaba;Khuda-Bukhsh, Anisur Rahman
    • Journal of Pharmacopuncture
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    • v.17 no.2
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    • pp.7-17
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    • 2014
  • Objectives: Condurango is widely used in various systems of complementary and alternative medicines (CAM) against oesophageal and stomach ailments including certain types of cancer. However, until now no systematic study has been conducted to verify its efficacy and dose with proper experimental support. Therefore, we examined if ethanolic extract of Condurango could ameliorate benzo[a]pyrene (BaP)-induced lung cancer in rats, in vivo to validate its use as traditional medicine. Methods: Fifteen male and 15 female Sprague-Dawley (SD) rats were treated with 0.28 mg/kg of Sweet Bee Venom (SBV) (high-dosage group) and the same numbers of male and female SD rats were treated with 0.2 mL/kg of normal saline (control group) for 13 weeks. We selected five male and five female SD rats from the high-dosage group and the same numbers of male and female SD rats from the control group, and we observed these rats for four weeks. We conducted body-weight measurements, ophthalmic examinations, urinalyses and hematology, biochemistry, histology tests. Results: A histological study revealed gradual progress in lung tissue-repair activity in Condurango-fed cancer-bearing rats, showing gradual tissue recovery after three months of drug administration. Condurango has the capacity to generate reactive oxygen species (ROS), which may contribute to a reduction in anti-oxidative activity and to an induction of oxidative stress-mediated cancer cell-death. Condurango-activated pro-apoptotic genes (Bax, caspase-3, caspase-9, p53, cytochrome-c, apaf-1, ICAD and PARP) and down-regulated antiapoptotic-Bcl-2 expression were noted both at mRNA and protein levels. Studies on caspase-3 activation and PARP cleavage by western blot analysis revealed that Condurango induced apoptosis through a caspase-3-dependent pathway. Conclusion: The anticancer efficacy of an ethanolic extract of Condurango for treating BaP-induced lung cancer in rats lends support for its use in various traditional systems of medicine.

Factors Influencing Competency in Evidence-based Practice among Clinical Nurses (간호사의 근거중심실무역량에 대한 영향요인)

  • Kim, Yeon-Sook;Kim, Jimee;Park, Mi-Mi
    • Journal of Korean Academy of Nursing Administration
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    • v.21 no.2
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    • pp.143-153
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    • 2015
  • Purpose: The aim of this study was to describe competency in evidence-based practice (EBP) among clinical nurses and to explore critical thinking disposition (CTD) and organizational culture (OC) as possible predictors for competency in EBP. Also this study was conducted to identify baseline data for purpose of developing evidence-based OC to ensure safety of patients and to improve quality of nursing services in clinical setting. Methods: With a descriptive correlation study design, a competency in EBP questionnaire was administered to a convenience sample of nurses (N=393) from a single general hospital in Gyeonggi Province. Results: The overall mean score for competency in EBP was $3.03{\pm}0.53$. Factors influencing competency in EBP were education (${\beta}=0.23$, p<.001), attendance at lectures on EBP (${\beta}=0.18$, p<.001), intellectual eagerness & healthy skepticism (${\beta}=0.27$, p<.001) among CTD, and hierarchy-oriented OC (${\beta}=0.14$, p=.005), which explained about 35% of the total variance. Conclusion: Critical thinking and competency in EBP should be part of nursing education especially for undergraduate students as well as strengthening clinical practice by activation of EBP. The results of this study that hierarchy-oriented OC, is a significant predictor for competency in EBP is difficult to accept. Its seemed to require further exploration.

The Effects of Cobrotoxin on $NF-{\kappa}B$ Activation in Human Prostatic Cancer Cell Line(PC-3) (Cobrotoxin이 전립선 암세포 $NF-{\kappa}B$ 활성에 미치는 영향)

  • Chae, Sang-Jin;Song, Ho-Seub
    • Journal of Acupuncture Research
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    • v.22 no.5
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    • pp.37-48
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    • 2005
  • Objectives : The purpose of this study was to investigate the anti-caner effect of cobrotoxin on the prostatic cancer cell line(PC-3). Methods : After the treatment of PC-3 cells with cobrotoxin, we performed fluorescence microscope, MTT assay, Western blotting, Flow cytometry, PAGE electrophoresis and Surface plasmon resonance analysis to identify $NF-{\kappa}B$ the change of calcium and NO. Results : 1. The expression of $NF-{\kappa}B$ was decreased at 1nM and It·as decreased significantly at 2, 4, 8nM. 2. $I{\kappa}B,\;NF-{\kappa}B$ inhibitor, was decreased significantly at 8nM and $p-l{\kappa}Ba$, phosphrylation of $I{\kappa}B$, was decreased significantly at all concentrations of cobrotoxin. 3. The expressions of p50 and p65 were decreased significantly and dose-dependently at 1, 2, 4, 8nM. 4. The expression of p53 was increased significantly at 1, 2, 4, 8nM. 5. The calcium concentration in cell wasn't changed at 1, 2, 4, 8nM, but was increased dose-dependently at 30, 70, 130, 250nM comparing with lower dose of cobrotoxin. 6. The NO concentration in cell was increased significantly at 1, 2, 4, 8nM. 7. In immunochemical staining, we found that cobrotoxin-immunochemical complex move into intracellular space dose-dependently. Conclusion : These results indicate that cobrotoxin has anti-cancer effects by inducing apoptosis.

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Immune Responses Induced by HSP60 DNA Vaccine against Toxoplasma gondii Infection in Kunming Mice

  • Li, Zhong-Yuan;Lu, Jing;Zhang, Nian-Zhang;Chen, Jia;Zhu, Xing-Quan
    • Parasites, Hosts and Diseases
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    • v.56 no.3
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    • pp.237-245
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    • 2018
  • Toxoplasma gondii can infect all the vertebrates including human, and leads to serious toxoplasmosis and considerable veterinary problems. T. gondii heat shock protein 60 (HSP60) is associated with the activation of antigen presenting cells by inducing initial immune responses and releasing inflammatory cytokines. It might be a potential DNA vaccine candidate for this parasite. A pVAX-HSP60 DNA vaccine was constructed and immune responses was evaluated in Kunming mice in this study. Our data indicated that the innate and adaptive immune responses was elicited by successive immunizations with pVAX-HSP60 DNA, showing apparent increases of CD3e+CD4+ and CD3e+CD8a+ T cells in spleen tissues of the HSP60 DNA-immunized mice ($24.70{\pm}1.23%$ and $10.90{\pm}0.89%$, P<0.05) and higher levels of specific antibodies in sera. Furthermore, the survival period of the immunized mice ($10.53{\pm}4.78day$) were significantly prolonged during the acute T. gondii infection. Decrease of brain cysts was significant in the experimental group during the chronic infection (P<0.01). Taken together, TgHSP60 DNA can be as a vaccine candidate to prevent the acute and chronic T. gondii infections.

Apoptotic pathway of SNU-1, human gastric cancer cell line, by Bodusan (보두산에 의한 사람 위암 세포주 SNU-1의 세포사멸 경로)

  • Lee, Jae-Eun;Yun, Hyun-Joung;Lee, Young-Tae;Bae, Chang-Wook;Jeun, Hyun-Sook;Park, Sun-Dong
    • The Korea Journal of Herbology
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    • v.21 no.1
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    • pp.33-42
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    • 2006
  • Objectives : The purpose of this study was to investigate the anticancer effects of Bodusan (BDS) on SNU-1 cells, a human gastric cancer cell line. Methods : To study the cytotoxic effect of BDS on SNU-1 cells, the cells were treated with various concentrations of BDS and then cell viability was determined by XTT reduction method and trypan blue exclusion assay. The typical signs of apoptosis, was examined by western blot analysis. BDS-induced MAPK activation was also examined by Western blot for phosphorylated ERK and p38. Results : BDS reduced proliferation of SNU-1 cells in a dose-dependent manner and decreased procaspase 3 level in a dose-dependent manner and induced the clevage of PARP at concentration > 500 ${\mu}g/ml$. BDS also triggered the mitochondrial apoptotic signaling by increasing the release of cytochrome C from mitochondria to cytosol and reducing the level of anti-apoptotic Bcl-2. BDS significantly decreased ERK phosphorylation and increased p38 phosphorylation in a dose-dependent manner. Futhermore, BDS treatment up-regulated p53 and p21waf expression in a dose-dependent manner. Conclusion : BDS-induced apoptosis is MAP kinase-dependent apoptoric pathway and arrested SNU-1 cells at the G0/G1 of cell cycle. These results suggest that BDS is potentially useful as a chemotherapeutic agent in human gastric cancer.

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Herbal medicine In-Jin-Ho-Tang as a potential anti-cancer drug by induction of apoptosis in human hepatoma HepG2 cells. (사람 간암 세포주인 HepG2에 대한 인진호탕(茵陳蒿湯)의 항암 효과)

  • Yun, Hyun-Joung;Kim, Byung-Wan;Lee, Chang-Hyun;Jung, Jae-Ha;Heo, Sook-Kyung;Park, Won-Hwan;Park, Sun-Dong
    • The Korea Journal of Herbology
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    • v.22 no.3
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    • pp.27-37
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    • 2007
  • Objectives: Hepatocellular carcinoma is the most common primary malignant tumor of the liver worldwide. In-Jin-Ho-Tang(IJHT) has been used as a traditional Chinese herbal medicine since ancient time. and today it is widely applied as a medication for jaundice which is associated with inflammation in liver. In this study, I investigated whether methanol extract of IJHT induced HepG2 cancer cell death. Methods: Cytotoxic activity of IJHT on HepG2 cells was using XTT assay. Apoptosis induction by Ros A in HCT116 cells was verified by the induction of cleavage of poly ADP-ribose polymerase (PARP). and activation of caspase-3, -8 and -9. The release of cytochrome c from mitochondria to cytosol. the level of Bcl-2 and Bax and the expression of p53 and p21 were examined by western blotting analysis. Furthermore, MAPKs activation was analyzed by western blotting analysis. Results: IJHT induced apoptosis in HepG2 cells. And treatment of IJHT resulted in the release of cytochrome c into cytosol, decreased anti-apoptotic Bcl-2, and increased pri-apoptotic Bax expression. IJHT markedly inactivated extracellular signal-regulated kinase (ERK1/2), and activated p38 mitogen-activated protein (MAP) kinase. Sodium orthovanadate (SOV), a phosphatase inhibitor, to reverse IJHT-induced ERK1/2 inactivation and SB203580, a specific p38 MAP Kinase inhibitor efficiently blocked apoptosis of HepG2. Thus, IJHT induces apoptosis in HepG2 cells via MAP kinase modulation. Conclusion: These results indicated that IJHT has some potential for use as an anti-cancer agent.

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Induction of Apaopotis by Water Extract of Cordyceps militaris (WECM) in Human Hepatocellular Carcinoma HepG2 Cells. (동충하초 열수 추출물에 의한 인체 간암세포 성장억제 및 apoptosis 유발에 관한 연구)

  • Kim, Kyung-Mi;Park, Cheol;Choi, Yung-Hyun;Lee, Won-Ho
    • Journal of Life Science
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    • v.18 no.6
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    • pp.804-813
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    • 2008
  • Cordyceps militaris, the Chinese medicinal fungal genus Cordyceps, is reported to possess many pharmacological activities including immunological stimulating, anti-cancer, anti-virus and anti-infection activities. However, the molecular mechanisms of C. militaris on biochemical actions in cancer have not been clearly elucidated yet. In the present study, we investigated the anti-proliferative activity of the water extract of C. militaris (WECM) in human hepatocellular carcinoma HepG2 cells. It was found that WECM could inhibit the cell growth in a dose-dependent manner, which was associated with morphological changes and apoptotic cell death such as formation of apoptotic bodies and increased populations of apoptotic sub-G1 phase. Apoptotic cell death of HepG2 cells by WECM was connected with a up-regulation of pro-apoptotic Bax expression, tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 (WAF1/CIP1). In addition, WECM treatment induced the proteolytic activation of caspase-3 and a concomitant degradation and/or inhibition of poly (ADP-ribose) polymerase (PARP), ${\beta}-catenin$ and phospholipase $(PLC)-{\gamma}1$ protein. Furthermore, caspase-3 inhibitor, z-DEVD-fmk, significantly inhibited WECM-induced apoptosis demonstrating the important role of caspase-3 in the observed cytotoxic effect. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of C. militaris.

Comparison of the mechanical efficacy of sonic activated irrigation and passive ultrasonic irrigation for intracanal medicaments removal

  • Jang, Ju-Kyong;Kwak, Sangwon;Choi, Ga Young;Ha, Jung-Hong;Choi, Sung-Baik;Kim, Hyeon-Cheol
    • The Journal of the Korean dental association
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    • v.53 no.10
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    • pp.743-750
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    • 2015
  • Objectives: This study compared the mechanical efficacy of sonic activated and passive ultrasonic irrigation for removing intracanal medicament from a simulated root canal under controlled conditions. Materials and Methods: Thirty simulated root canal in resin blocks were randomly divided into 3-groups. The canals were enlarged using ProTaper files and K3XF (#30/0.06). After cleaning and drying, canals were filled with Calcipex. Overfilled materials were wiped out and measured their weight to the unit of 1/10mg. After one week storage in 100% humidity $37^{\circ}C$ temperature, canals were irrigated using 20mL of saline with one of following methods according to the designated groups (n = 10). For group-NI, 30-gauge nickel-titanium irrigation needle was used. During irrigation with every 5mL, needle was moved in-and-out with 4-mm amplitudes. EndoActivator and ultrasonic tip were used for group-EA and group-UT respectively for 20 seconds after every 5mL irrigation using needle. Then the weight was measured again to calculate the weight of residual remnants. The data were analyzed by one-way ANOVA and Duncan's post-hoc test at a significance level of 95%. Results: The weight of the residual medicaments were $3.62{\pm}0.81mg$, $2.84{\pm}0.28mg$, and $2.73{\pm}0.90mg$ for group-NI, -EA, and -UT, respectively. Group-EA and group-UT had no significant differences to remove intracanal medicament and left significantly less amount of paste than group-NI (p < 0.05). Conclusions: Under the controlled conditions of this study, the sonic activation and PUI have similar mechanical efficacy for removing intracanal medicament.

Effects of Protein Kinase C Modulation on Hepatic Hemodynamics and Glucoregulation

  • Lee, Joong-Woo;Kong, In-Deok;Park, Kyu-Sang;Chung, Hae-Sook;Filkins, James P.
    • The Korean Journal of Physiology and Pharmacology
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    • v.3 no.6
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    • pp.571-578
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    • 1999
  • This study evaluated the effects of PKC activation using phorbol 12-myristate 13-acetate (PMA) and PKC inhibition using the isoquinoline sulfomide derivative H-7 on hemodynamics and glucoregulation in the isolated perfused rat liver. Livers were isolated from fed male Holtzman rats and perfused with Krebs Ringer bicarbonate solution under a constant flow of 50 ml/min at $35^{\circ}C.$ Portal vein pressure, glucose and lactate concentrations in the medium and oxygen consumption rates were continuously monitored by a Grass polygraph, YSI glucose and lactate monitors, and a YSI oxygen monitor, respectively. PMA at concentration of 2 to 200 nM increased the portal vein pressure, glucose and lactate production, but decreased oxygen consumption rate in a dose-dependent fashion. H-7 $(200\;{\mu}M)$ attenuated PMA (50 nM)-induced vasoconstriction $(15.1{\pm}1.36\;vs\;10.56{\pm}1.17\;mmHg),$ glucose production rate $(91.3{\pm}6.15\;vs\;71.8{\pm}2.50\;{\mu}moles/g/hr),$ lactate production rate $(72.4{\pm}6.82\;vs\;53.6{\pm}4.82\;{\mu}moles/g/hr)$ and oxygen consumption rate $(33.7{\pm}1.41\;vs\;27.9{\pm}1.75\;{\mu}l/g/min).$ The effects of PMA were blocked either by addition of verapamil $(9\;{\mu}M)$ or perfusion with $Ca^{2+}-free$ KRB. These results suggest that the hemodynamic and glucoregulatory changes in the perfused rat liver are mediated by protein kinase C activation and require $Ca^{2+}$ influx from the extracellular fluid.

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