• Title/Summary/Keyword: Nuclear factor 1

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Therapeutic Angiogenesis by Intramyocardial Injection of pCK-VEGF165 in Pigs (돼지에서 pCK-VEGF165의 심근내 주입에 의한 치료적 혈관조성)

  • Choi Jae-Sung;Han Woong;Kim Dong Sik;Park Jin Sik;Lee Jong Jin;Lee Dong Soo;Kim Ki-Bong
    • Journal of Chest Surgery
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    • v.38 no.5 s.250
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    • pp.323-334
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    • 2005
  • Background: Gene therapy is a new and promising option for the treatment of severe myocardial ischemia by therapeutic angiogenesis. The goal of this study was to elucidate the efficacy of therapeutic angiogenesis by using VEGF165 in large animals. Material and Method: Twenty-one pigs that underwent ligation of the distal left anterior descending coronary artery were randomly allocated to one of two treatments: intramyocardial injection of pCK-VEGF (VEGF) or intramyocardial injection of pCK-Null (Control). Injections were administered 30 days after ligation. Seven pigs died during the trial, but eight pigs from VEGF and six from Control survived. Echo-cardiography was performed on day 0 (preoperative) and on days 30 and 60 following coronary ligation. Gated myocardial single photon emission computed tomography imaging (SPECT) with $^{99m}Tc-labeled$ sestamibi was performed on days 30 and 60. Myocardial perfusion was assessed from the uptake of $^{99m}Tc-labeled$ sestamibi at rest. Global and regional myocardial function as well as post-infarction left ventricular remodeling were assessed from segmental wall thickening; left ventricular ejection fraction (EF); end systolic volume (ESV); and end diastolic volume (EDV) using gated SPECT and echocardiography. Myocardium of the ischemic border zone into which pCK plasmid vector had been injected was also sampled to assess micro-capillary density. Result: Micro-capillary density was significantly higher in the VEGF than in Control ($386\pm110/mm^{2}\;vs.\;291\pm127/mm^{2};\;p<0.001$). Segmental perfusion increased significantly from day 30 to day 60 after intramyocardial injection of plasmid vector in VEGF ($48.4\pm15.2\%\;vs.\;53.8\pm19.6\%;\;p<0.001$), while no significant change was observed in the Control ($45.1\pm17.0\%\;vs.\;43.4\pm17.7\%;\;p=0.186$). This resulted in a significant difference in the percentage changes between the two groups ($11.4\pm27.0\%\;increase\;vs.\;2.7\pm19.0\%\;decrease;\;p=0.003$). Segmental wall thickening increased significantly from day 30 to day 60 in both groups; the increments did not differ between groups. ESV measured using echocardiography increased significantly from day 0 to day 30 in VEGF ($22.9\pm9.9\;mL\;vs.\;32.3\pm9.1\;mL;\; p=0.006$) and in Control ($26.3\pm12.0\;mL\;vs.\;36.8\pm9.7\;mL;\;p=0.046$). EF decreased significantly in VEGF ($52.0\pm7.7\%\;vs.\;46.5\pm7.4\%;\;p=0.004$) and in Control ($48.2\pm9.2\%\;vs.\;41.6\pm10.0\%;\;p=0.028$). There was no significant change in EDV. The interval changes (days $30\~60$) of EF, ESV, and EDV did not differ significantly between groups both by gated SPECT and by echocardiography. Conclusion: Intramyocardial injection of pCK-VEGF165 induced therapeutic angiogenesis and improved myocardial perfusion. However, post-infarction remodeling and global myocardial function were not improved.

Development of Movement Analysis Program and its Feasibility Test in Streotactic Body Radiation Threrapy (복부부위의 체부정위방사선치료시 호흡에 의한 움직임분석 프로그램 개발 및 유용성 평가)

  • Shin, Eun-Hyuk;Han, Young-Yih;Kim, Jin-Sung;Park, Hee-Chul;Shin, Jung-Suk;Ju, Sang-Gyu;Lee, Ji-Hea;Ahn, Jong-Ho;Lee, Jai-Ki;Choi, Doo-Ho
    • Progress in Medical Physics
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    • v.22 no.3
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    • pp.107-116
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    • 2011
  • Respiratory gated radiation therapy and stereotactic body radiation therapy require identical tumor motions during each treatment with the motion detected in treatment planning CT. Therefore, this study developed a tumor motion monitoring and analysis system during the treatments employing RPM data, gated setup OBI images and a data analysis software. A respiratory training and guiding program which improves the regularity of breathing was used to patients. The breathing signal was obtained by RPM and the recorded data in the 4D console was read after treatment. The setup OBI images obtained gated at 0% and 50% of breathing phases were used to detect the tumor motion range in crenio-caudal direction. By matching the RPM data recorded at the OBI imaging time, a factor which converts the RPM motion to the tumor motion was computed. RPM data was entered to the institute developed data analysis software and the maximum, minimum, average of the breathing motion as well as the standard deviation of motion amplitude and period was computed. The computed result is exported in an excel file. The conversion factor was applied to the analyzed data to estimate the tumor motion. The accuracy of the developed method was tested by using a moving phantom, and the efficacy was evaluated for 10 stereotactic body radiation therapy patients. For the sine wave motion of the phantom with 4 sec of period and 2 cm of peak-to-peak amplitude, the measurement was slightly larger (4.052 sec) and the amplitude was smaller (1.952 cm). For patient treatment, one patient was evaluated not to qualified to SBRT due to the usability of the breathing, and in one patient case, the treatment was changed to respiratory gated treatment due the larger motion range of the tumor than treatment planed motion. The developed method and data analysis program was useful to estimate the tumor motion during treatment.

A Methanol Extract of Adansonia digitata L. Leaves Inhibits Pro-Inflammatory iNOS Possibly via the Inhibition of NF-κB Activation

  • Ayele, Yihunie;Kim, Jung-Ah;Park, Eunhee;Kim, Ye-Jung;Retta, Negussie;Dessie, Gulelat;Rhee, Sang-Ki;Koh, Kwangoh;Nam, Kung-Woo;Kim, Hee Seon
    • Biomolecules & Therapeutics
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    • v.21 no.2
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    • pp.146-152
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    • 2013
  • This study examined the total polyphenol content of eight wild edible plants from Ethiopia and their effect on NO production in Raw264.7 cells. Owing to its relatively high polyphenol concentration and inhibition of NO production, the methanol extract of Adansonia digitata L. leaf (MEAD) was subjected to detailed evaluation of its antioxidant and anti-inflammatory effects. Antioxidant effects were assessed by measuring free-radical-scavenging activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and oxygen-radical-absorbance capacity (ORAC) assays, while anti-inflammatory effects were assessed by measuring inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. In the ORAC assay, MEAD was 10.2 times more potent than vitamin C at eliminating peroxyl radicals. In DPPH assay, MEAD also showed a strong ROS scavenging effect. MEAD significantly inhibited iNOS activity ($IC_{50}=28.6{\mu}g/ml$) of LPS-stimulated Raw264.7 cells. We also investigated the relationship between iNOS expression and nuclear factor kappa B (NF-${\kappa}B$) activation. MEAD inhibited $I{\kappa}B{\alpha}$ degradation and NF-${\kappa}B$ translocation from the cytosol to the nucleus in LPS-induced RAW264.7 cells without significant cytotoxic effects, as confirmed by MTT assay. These results suggest that MEAD inhibits anti-inflammatory iNOS expression, which might be related to the elimination of peroxyl radicals and thus the inhibition of $I{\kappa}B{\alpha}$-mediated NF-${\kappa}B$ signal transduction.

Anti-Inflammatory Effect of Grateloupia imbricata Holmes Ethanol Extract on LPS-Induced RAW 264.7 Cells (꽃지누아리 에탄올 추출물의 LPS로 유도된 RAW 264.7 세포에 대한 항염증 효과)

  • Kim, Min-Ji;Bae, Nan-Yong;Kim, Koth-Bong-Woo-Ri;Park, Ji-Hye;Park, Sun-Hee;Choi, Jung-Su;Ahn, Dong-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.2
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    • pp.181-187
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    • 2016
  • Algae is a potential resource with various biological activities. In this study, the anti-inflammatory effect of Grateloupia imbricata Holmes ethanol extract (GIHEE) from red algae was investigated in LPS-induced RAW 264.7 cells. As a result, reduced secretion of pro-inflammatory cytokines [tumor necrosis factors-${\alpha}$, interleukin (IL)-$1{\beta}$, and IL-6] and nitric oxide (NO) was observed in a dose-dependent manner. Expression of nuclear factor-kappaB (NF-${\kappa}B$) as well as inducible NO synthase and cyclooxygenase-2 proteins was reduced by GIHEE, suggesting that the anti-inflammatory activity of GIHEE is related to suppression of NF-${\kappa}B$ signaling pathways. In addition, GIHEE reduced phosphorylation of mitogen-activated protein kinases. These results suggest that GIHEE can be used as a potential anti-inflammatory therapeutic.

Numerical Design of Double Quantum Coherence Filter for the Detection of Myo-Inositol In vivo (인체 내 myo-Inositol 검출을 위한 수치해석적 이중양자 필터 디자인)

  • Lee, Yun-Jung;Jung, Jin-Young;Noh, Hyung-Joon;Yu, Ung-Sik;Kim, Hyeon-Jin
    • Investigative Magnetic Resonance Imaging
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    • v.13 no.2
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    • pp.117-126
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    • 2009
  • Purpose : A numerical method of designing a multiple quantum filter (MQF) is presented for the optimum detection of myo-inositol (mI), an important brain metabolite, by using in vivo proton nuclear magnetic resonance spectroscopy ($^1$-HMRS). Materials and Methods : Starting from the characterization of the metabolite, the filter design includes the optimization of the sequence parameters such as the two echo times (TEs), the mixing time (TM), and the flip angle and offset frequency of the 3rd $90^{\circ}$ pulse which converts multiple quantum coherences (MQCs) back into single quantum coherences (SQCs). The optimized filter was then tested both in phantom and in human brains. Results : The results demonstrate that the proposed MQF can improve the signal-to-background ratio of the target metabolite by a factor of more than three by effectively suppressing the signal from the background metabolites. Conclusion : By incorporating a numerical method into the design of MQFs in $^1$-HMRS the spectral integrity of a target metabolite, in particular, with a complicated spin system can be substantially enhanced.

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Structure and Growth of Tin Whisker on Leadframe with Lead-free Solder Finish (무연솔더 도금된 리드프레임에서 Sn 위스커의 성장과 구조)

  • Kim Kyung-Seob;Leem Young-Min;Yu Chong-Hee
    • Journal of the Microelectronics and Packaging Society
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    • v.11 no.3 s.32
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    • pp.1-7
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    • 2004
  • Tin plating on component finishes may grow whiskers under certain conditions, which may cause failures in electronics equipment. To protect the environment, 'lead-free' among component finishes is being promoted worldwide. This paper presents the evaluation results of whiskers on two kinds of lead-free plating materials at the plating temperature and under the reliability test. The rising plating temperature caused increasing the size of plating grain and shorting the growth of whisker. The whisker was grown under the temperature cycling the bent type in matt Sn plating and striated type in malt Sn-Bi. The whisker growth in Sn-Bi plating was shorter than that in Sn plating. In FeNi42 leadframe, the $7.0{\~}10.0{\mu}m$ diameter and the $25.0{\~}45.0{\mu}m$ long whisker was grown under 300 cycles. In the 300 cycles of Cu leadframe, only the nodule(nuclear state) grew on the surface, and in the 600 cycles, a $3.0{\~}4.0{\mu}m$ short whisker grew. After 600 cycles, the ${\~}0.34{\mu}m$ thin $Ni_3Sn_4$ formed on the Sn-plated FeNi42. However, we observed the amount of $0.76{\~}1.14{\mu}m$ thick $Cu_6Sn_5$ and ${\~}0.27{\mu}m$ thin $Cu_3Sn$ intermetallics were observed between the Sn and Cu interfaces. Therefore, the main growth factor of a whisker is the intermetallic compound in the Cu leadframe, and the coefficient of thermal expansion mismatch in FeNi42.

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Effect of Low Intensity Pulsed Ultrasound with Adipose-Derived Stem Cells on Bone Healing around a Titanium Implant in Tibia of Osteoporosis-Induced Rats (골다공증 유도 백서 경골에 티타늄 임플랜트 매식 시 지방조직유래 줄기세포 주입과 저출력 초음파 적용이 골치유에 미치는 영향)

  • Lee, Kwang-Ho;Choi, Yeon-Sik;Shin, Sang-Hun;Chung, In-Kyo;Kim, Gyoo-Cheon;Kim, Cheol-Hun;Kim, Uk-Kyu
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.33 no.3
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    • pp.199-209
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    • 2011
  • Purpose: Osteoporosis, is a major health problem for the elderly and post-menopausal women and shown to alter the properties of bone as well as impair bone healing around titanium implants in both human and animals. The objective of this study was to examine the effect of LIPUS with adipose-derived stem cells on the healing process around a titanium implant in rats with osteoporosis. Methods: Sixteen osteoporosis-induced rats were divided into two groups: an adipose-derived stem cell injected with Low Intensity Pulsed Ultrasound (LIPUS) application group and a control group. Titanium screw implants (diameter, 2.0 mm: length, 3.5 mm, Cowell Medi, Korea) were placed into both tibia of 16 rats, on 8 rats as the control group and the other 8 rats as the experimental group. Rats were sacrificed at different intervals from 1, 2, 4 and 8 weeks after implantation for histopathologic and immunohistochemical analyses. Results: Histopathological analysis revealed newly formed bone in experimental group earlier than that in control group. Especially at 1 week after implantation, more amounts of new bone matrix and collagen around the implant in the experimental group were seen compared with the control group. Immunohistochemical analysis showed that the levels of osteoprotegerin (OPG) expression in the experimental group were increased at early stages compared with that of control group until 2 weeks after implantation. But after 2 weeks, the expression level of OPG similar in both groups. The expression levels of receptor activator of nuclear factor kB ligand (RANKL) were stronger in the experimental group than the control group until 2 weeks after implantation. After 4 weeks, expression of RANKL in experimental group was similar to the control group. Conclusion: The results of this study suggest that LIPUS with Adipose-Derived Stem Cells in implantation could promote bone healing around titanium implants in rats with osteoporosis.

Effect of adipose-derived stem cells on bone healing on titanium implant in tibia of diabetes mellitus induced rats (당뇨 유도 백서 경골에 매식한 티타늄 임플란트 주위에 지방조직 유래 줄기세포 적용 시 골치유에 미치는 영향)

  • Kim, Min-Gu;Jung, In-Kyo;Shin, Sang-Hun;Kim, Chul-Hoon;Kim, Bok-Joo;Kim, Jung-Han;Hwang, Young-Sup;Jung, Eu-Gene;Kim, Jin-Woo;Kim, Uk-Kyu
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.36 no.5
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    • pp.392-401
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    • 2010
  • Introduction: Diabetes mellitus, as a major health problem for the elderly has been shown to alter the properties of the bone and impair bone healing around a titanium implant in both humans and animals. The aim of this study was to examine the effect of adipose-derived stem cells on the healing process around a titanium implant in streptozotocin-induced diabetic rats. Materials and Methods: Thirteen rats were divided into two groups: adipose-derived stem cells injected group and a control group. A titanium screw implant (diameter: 2.0 mm, length: 3.5 mm) was placed into both tibia of 13 rats: 13 right tibia as the control group and 13 left tibia as the experimental group. The rats were sacrificed at different intervals (1, 2, and 4 weeks) after implantation for histopathology observations and immunohistochemistric analysis. Results: The histopathological findings revealed earlier new formed bone in the experimental group than the control group. In particular, at 1 week after implantation, the experimental group showed more newly formed bone and collagen around the implant than the control group. In immunohistochemistric analysis, osteoprotegerin (OPG) expression in the experimental group increased early compared to that of the control group until 2 weeks after implantation. However, after 2 weeks, OPG expression in the experimental group was similar to OPG expression in the control group. The receptor activator of nuclear factor ${\kappa}B$ ligand (RANKL) expression in the experimental group increased early compared to that of the control group, and then decreased at 2 weeks. After 2 weeks, the level of RANKL expression was similar in both groups. Conclusion: These results suggest that adipose-derived stem cells in implantation can promote bone healing around titanium, particularly in diabetes mellitus induced animals.

Anti-Inflammatory Effects of Extracts from Caesalpinia sappan L. on Skin Inflammation (TPA로 유도된 마우스 귀 부종 동물모델에서 소목추출물의 항염증 효과)

  • Eum, Won Sik;Lee, Kwang-Jae;Kim, Dae Won;Lim, Soon Sung;Kang, Il-Jun;Park, Jinseu;Choi, Soo Young
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.3
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    • pp.384-388
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    • 2013
  • This study investigated the anti-inflammatory effects of extracts from Caesalpinia sappan L. (CSL) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema in mice. Skin inflammation was detected by immunohistochemistry and the protein and mRNA expression levels of cyclooxygenase-2 (COX-2) and cytokines (IL-6, IL-$1{\beta}$ and TNF-${\alpha}$) detected by Western blotting and RT-PCR. The activation of nuclear factor-kappa B (NF-${\kappa}B$) and mitogen-activated protein kinase (MAPK) were analyzed by Western blotting. CSL extracts markedly inhibited the TPA-induced expression of COX-2 and pro-inflammatory cytokines. Also, CSL extracts significantly reduced the activation of NF-${\kappa}B$ and MAPK. These results suggest that CSL extracts may serve as therapeutic agents against skin diseases related to inflammation.

CLINICAL IMPLICATIONS OF TELOMERASE ACTIVITY IN ORAL SQUAMOUS CELL CARCIMOMA (구강편평세포암에서 telomerase 활성도의 임상적 연관성에 관한 연구)

  • Shim, Yu-Jin;Kim, Myung-Jin;Nahm, Dong-Seok;Lee, Jong-Ho
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.27 no.4
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    • pp.289-300
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    • 2001
  • Telomerase is a ribonucleoprotein that synthesizes telomere repeats. It has been reported that activation of telomerase was associtated with immortalization, proliferative activity and carcinogenesis. Recently, telomerase activity has been extensively studied in many kinds of malignant tumors for clinical diagnostic and/or prognostic utilities. In neuroblastoma, breast carcinoma, gastric carcinoma, non-small cell lung carcinoma, close relationship has been reported between high telomerase activity and lymph node metastasis, tumor aggressiveness and poor prognosis. The purpose of this study is to investigate the clinical implication of telomerase activity assay as an adjunctive factor in decision-making on neck node management, speedy pre-operative judging on histologic malignancy grading. Thus we performed semi-quantitative assay of telomerase activity using Telomerase PCR ELISA $kit^{(R)}$(Boeringer Manheim, Germany) and evaluated correlation between telomerase activity and tumor size, neck node metastasis, Anneroth malignancy score and influence of pre-operative chemotherapy on its activity in 27 cases of oral squamous cell carcinomas and 18 cases of normal oral epithelium. Also, correlation between telomerase activities and PCNA indices was evaluated. The results were obtained as follows: 1. The telomerase activities were detected in 24 specimens out of 27 oral squamous cell carcinoma specimens (88.9%) and in 5 specimens out of 18 normal oral epithelium specimens (27.8%). The mean value of telomerase activities was $0.9793{\pm}0.3428$ in 24 oral squamous cell carcinoma specimens and $0.4855{\pm}0.1117$ in 5 normal oral epithelium specimens. The positivity rate and mean value of telomerase activities in oral squamous cell carcinoma specimens were significantly higher than those of normal oral epithelium specimens (p<0.05). 2. There was no significant correlation between total Anneroth malignancy score and telomerase activity (p>0.05), but points of mitosis index and depth of invasion were significantly correlated with telomerase activities (p<0.05). 3. The positive immunohistochemical staining for PCNA(proliferating cell nuclear antigen) was observed in 26 specimens out of 27 oral squamous cell carcinoma specimens and mean value of PCNA indices of 26 specimens was $53.67{\pm}26.46$. PCNA indices were significantly correlated with telomerase activities (p<0.05). 4. The mean value of telomerase activities was significantly higher in pathologic T3/T4 group than in T1/T2 group (p<0.01). There was no significant difference of mean value of telomerase activities between pathologic neck node positive group and negative group (p> 0.05). Pre-operative chemotherapy significantly lowered the telomerase activities (p<0.05). The above results suggested telomerase activity could be used as diagnostic marker and adjunctive parameter for judging on histologic malignancy in oral squamous cell carcinoma.

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