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Reactive oxygen species-dependent apoptosis induction by water extract of Citrus unshiu peel in MDA-MB-231 human breast carcinoma cells

  • Kim, Min Yeong;Choi, Eun Ok;HwangBo, Hyun;Kwon, Da He;Ahn, Kyu Im;Kim, Hong Jae;Ji, Seon Yeong;Hong, Su-Hyun;Jeong, Jin-Woo;Kim, Gi Young;Park, Cheol;Choi, Yung Hyun
    • Nutrition Research and Practice
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    • v.12 no.2
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    • pp.129-134
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    • 2018
  • BACKGROUND/OBJECTIVES: Although several recent studies have reported the anti-cancer effects of extracts or components of Citrus unshiu peel, which has been used for various purposes in traditional medicine, the molecular mechanisms for their effects remain unclear. In the present study, the anti-cancer activity of a water-soluble extract of C. unshiu peel (WECU) in MDA-MB-231 human breast carcinoma cells at the level of apoptosis induction was investigated. MATERIALS/METHODS: Cytotoxicity was evaluated using the MTT assay. Apoptosis was detected using DAPI staining and flow cytometry analyses. Mitochondrial membrane potential, reactive oxygen species (ROS) assay, caspase activity and Western blotting were used to confirm the basis of apoptosis. RESULTS: The results indicated that WECU-induced apoptosis was related to the activation of caspase-8, and -9, representative initiator caspases of extrinsic and intrinsic apoptosis pathways, respectively, and caspase-3 accompanied by proteolytic degradation of poly(ADP-ribose) polymerase and down-regulation of the inhibitors of apoptosis protein family members. WECU also increased the pro-apoptotic BAX to anti-apoptotic BCL-2 ratio, loss of mitochondrial membrane potential and cytochrome c release from mitochondria to cytoplasm. Furthermore, WECU provoked the generation of ROS, but the reduction of cell viability and induction of apoptosis by WECU were prevented when ROS production was blocked by antioxidant N-acetyl cysteine. CONCLUSIONS: These results suggest that WECU suppressed proliferation of MDA-MB-231 cells by activating extrinsic and intrinsic apoptosis pathways in a ROS-dependent manner.

Smad6 Gene and Suppression of Radiation-Induced Apoptosis by Genistein in K562 Cells (K562 세포주에서 Genistein에 의해 억제되는 Radiation-induced Apoptosis의 조절 유전자)

  • Jeong, Soo-Jin;Jin, Young-Hee;Yoo, Yeo-Jin;Do, Chang-Ho;Jeong, Min-Ho;Huh, Gi-Yeong;Bae, Hye-Ran;Yang, Kwang-Mo;Moon, Chang-Woo;Oh, Sin-Geun;Hur, Won-Joo;Lee, Hyung-Sik
    • Radiation Oncology Journal
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    • v.19 no.3
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    • pp.245-251
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    • 2001
  • Prupose : The genes involved on the suppression or radiation-induced apoptosis by genistein in K562 leukemia cell line was investigated. Materials and methods : K562 cells in exponential growth phase were irradiated with a linear accelerator at room temperature. For X-ray irradiation and drug treatment, cultures were prepared at $2\times10^5\;cells/mL$. The cells were irradiated with 10 Gy (Clinac 1800C, Varian, USA), Stock solutions of herbimycin A (HMA, Calbiochem, UK) and genistein (Calbiochem, UK) were prepared in dimethylsulfoxide (DMSO, Sigma, UK). After incubation at $37^{\circ}C$ for 24 h, PCR-select cDNA subtractive hybridization, dot hybridization, DNA sequencing and Northern hybridization were examined. Results : Smad6 gene was identified from the differentially expressed genes in K562 cells incubated with genistein which had been selected by PCR-select cDNA subtractive hybridization. The mRNA expression of Smad6 in K562 cells incubated with genistein was also higher than control group by Northern hybridization analysis. Conclusion : We have shown that Smad6 involved on the suppression of radiation-induced apoptosis by genistein in K562 leukemia cell line. It is plausible that the relationship between Smad6 and the suppression of radiation-induced apoptosis is essential for treatment development based on molecular targeting designed to modify radiation-induced apoptosis.

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Preventive Action of Ribes diacanthum Pall. against High Blood Glucose Level in Alloxan-induced Diabetic Mice (가시까치밥나무(Ribes diacanthum Pall.) 추출물의 Alloxan 투여 마우스에서 혈당 상승 억제 효과)

  • Kim, Eun Sun;Birasuren, Bayarmaa;Kim, Mee Ree
    • Journal of the East Asian Society of Dietary Life
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    • v.23 no.1
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    • pp.53-60
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    • 2013
  • The preventive actions of methanol extracts from Ribes diacanthum Pall. (RDP) against high blood glucose levels in alloxan-induced diabetic mice were investigated. ICR mice (male, 8 wks) were divided into four experimental groups: a normal group (N), an alloxan-induced group (control), a RDP 1 mg/kg b.w./day + alloxan group (RDP-1) and a RDP 3 mg/kg b.w./day + alloxan group (RDP-2). Mice were fed RDP extracts for 14 days and then a diabetic condition induced by injecting alloxan (50 mg/kg b.w. i.v.). The total phenolic contents of RDP were 0.508 mg/g. Plasma glucose levels were significantly lower in RDP groups (RDP+alloxan) than the control (alloxan-induced diabetic group). In an oral glucose tolerance test, the glucose levels of RDP extract groups were significantly decreased compared to the control group. The levels of total cholesterol, triglycerides, AST, ALT, uric acid, and blood urea nitrogen in serum were lower in the RDP groups than the control group, whereas levels of HDL-cholesterol showed no difference between treatment groups. We conclude that RDP extracts positively influence blood glucose levels in diabetic mice.

Prediction of Patient Management in COVID-19 Using Deep Learning-Based Fully Automated Extraction of Cardiothoracic CT Metrics and Laboratory Findings

  • Thomas Weikert;Saikiran Rapaka;Sasa Grbic;Thomas Re;Shikha Chaganti;David J. Winkel;Constantin Anastasopoulos;Tilo Niemann;Benedikt J. Wiggli;Jens Bremerich;Raphael Twerenbold;Gregor Sommer;Dorin Comaniciu;Alexander W. Sauter
    • Korean Journal of Radiology
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    • v.22 no.6
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    • pp.994-1004
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    • 2021
  • Objective: To extract pulmonary and cardiovascular metrics from chest CTs of patients with coronavirus disease 2019 (COVID-19) using a fully automated deep learning-based approach and assess their potential to predict patient management. Materials and Methods: All initial chest CTs of patients who tested positive for severe acute respiratory syndrome coronavirus 2 at our emergency department between March 25 and April 25, 2020, were identified (n = 120). Three patient management groups were defined: group 1 (outpatient), group 2 (general ward), and group 3 (intensive care unit [ICU]). Multiple pulmonary and cardiovascular metrics were extracted from the chest CT images using deep learning. Additionally, six laboratory findings indicating inflammation and cellular damage were considered. Differences in CT metrics, laboratory findings, and demographics between the patient management groups were assessed. The potential of these parameters to predict patients' needs for intensive care (yes/no) was analyzed using logistic regression and receiver operating characteristic curves. Internal and external validity were assessed using 109 independent chest CT scans. Results: While demographic parameters alone (sex and age) were not sufficient to predict ICU management status, both CT metrics alone (including both pulmonary and cardiovascular metrics; area under the curve [AUC] = 0.88; 95% confidence interval [CI] = 0.79-0.97) and laboratory findings alone (C-reactive protein, lactate dehydrogenase, white blood cell count, and albumin; AUC = 0.86; 95% CI = 0.77-0.94) were good classifiers. Excellent performance was achieved by a combination of demographic parameters, CT metrics, and laboratory findings (AUC = 0.91; 95% CI = 0.85-0.98). Application of a model that combined both pulmonary CT metrics and demographic parameters on a dataset from another hospital indicated its external validity (AUC = 0.77; 95% CI = 0.66-0.88). Conclusion: Chest CT of patients with COVID-19 contains valuable information that can be accessed using automated image analysis. These metrics are useful for the prediction of patient management.

Effect of Antioxidants Plus Growth Factors on In Vitro Development of Porcine IVM/IVF Embryos (항산화제와 Growth Factor 혼합첨가가 돼지 체외수정란의 체외배양에 미치는 영향)

  • 최영진;박춘근;정희태;김정익;박동헌;장현용;장원경;박진기;양부근
    • Korean Journal of Animal Reproduction
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    • v.26 no.3
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    • pp.215-221
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    • 2002
  • Antioxidants(N-acetyl-1-cysteine, ebselen and glutathione) and growth factors(EGF, PDGF) were studied as a mean of increasing the development of porcine embryos produced by in vitro maturation (IVM) and in vitro fertilization(IVF). Porcine embryos developed to the 2~8 cell stage after IVF were cultured fer 6 to 7 days at 38.5$^{\circ}C$ in NCSU 23 medium containing antioxidants plus growth factors. Cell numbers of blastocysts were counted by fluorescence staining method. The developmental rate beyond morula stages in NCSU 23 containing NAC(1nm) or NAC(1nm) plus EGF(100ng/$m\ell$) or PDGF(5ng/$m\ell$) were 28.1, 32.3 and 35.3%, respectively. NAC plus PDGF group was slightly higher than control group(P>0.05). The developmental capacity in NCSU 23 containing ebselen(10 $\mu$M) or ebselen(10 $\mu$M) plus EGF(100ng/$m\ell$) or PDGF(5ng/$m\ell$) were 17.8, 36.9 and 40.3%, respectively Ebselen plus growth factor groups were significantly higher than control group(P<0.05). The developmental capacity in NCSU 23 containing glutathione(100 $\mu$M) or glutathione(100 $\mu$M) plus EGF (100ng/$m\ell$) or PDGF(5ng/$m\ell$) were 24.1, 30.5 and 27.7%, respectively. There were not difference in all experimental groups(P>0.05). In all experimental groups, there was no significantly differences on the cell number of blastocysts, but ebselen plus growth factor groups were significantly higher than control group. These studies indicate that antioxidants plus growth factors can increase the proportion of embryos that developed beyond morulae stage.

Effect of Korean Ginseng on the Expression of Transferrin Receptor in the Liver Cell Membrane of Rat (백서의 간세포막에서 Transferrin Receptor의 발현에 미치는 인삼의 영향)

  • Lim Jong-Ho;Hong Jang-Hee;Hur Gang-Min;Seok Jeong-Ho;Lee Jae-Heun
    • Journal of Ginseng Research
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    • v.23 no.2 s.54
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    • pp.105-114
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    • 1999
  • To investigate the effects of korean ginseng on the expression of transferrin receptor (TfR) in the liver cell membrane, we had carried out the experiments of $[^{3}H]thymidine$ uptake, $^{125}I-transferrin$ binding, and TfR mRNA expression in the liver after partial hepatectomy of normal and 3'-methyl-4-dimethylaminoa-zobenzene (3'-Me-DAB) treated rat with or without treatment of korean gingseng. $[^3H]thymidine$ uptake was not changed in the liver of 3'-Me-DAB or ginseng treated rat compared to that of control rat, but increased in that of partial hepatectomy of normal or 3'-Me-DAB treated rat. And this increased $[^{3}H]thymidine$ uptake was lowered slightly by the treatment of ginseng. Transferrin binding sites in the liver plasma membrane of ginseng treated rat with or without partial hepatectomy were similar, but increased in that of 3'-Me-DAB treated rat with or without partial hepatectomy compared to those of each control rat and these increased binding sites were reduced by ginseng treatment. Transferrin binding affinity (l/kd) was not changed by ginseng treatment, but tended to decrease in the liver of 3'-Me-DAB treated rat or in those after partial hepatectomy of all groups and reverse by ginseng treatment in 3'-Me-DAB treated rat. The expression of TfR mRNA was increased in the liver of 3'-Me-DAB treated rat with partial hepatectomy (peak at 24 hours), but lowered by ginseng treatment in this rat. From these results, it is suggested that korean ginseng has no effect on the increased expression of TfR with decreased affinity in the cell membrane of regenerated liver after partial hepatectomy of rat, but could inhibt that of 3'-Me-DAB treated rat through the regulation of DNA synthesis or TfR mRNA in partial.

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Video-Assisted Thoracic Surgery Lobectomy for Non-Small Cell Lung Cancer: Experience of 133 Cases (폐암에서의 흉강경 폐엽절제술 치험 133예)

  • Kim, Hyeong-Ryul;Cho, Jeong-Su;Jang, Hee-Jin;Lee, Sang-Cheol;Choi, Eun-Suk;Jheon, Sang-Hoon;Sung, Soak-Whan
    • Journal of Chest Surgery
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    • v.42 no.5
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    • pp.615-623
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    • 2009
  • Background: We evaluated the feasibility and the efficacy of Video-Assisted Thoracic Surgery (VATS) lobectomy for treating patients with non-small cell lung cancer (NSCLC) and we compared the outcomes of VATS lobectomy with those of open lobectomy. Material and Method: From 2003 to March 2008, 133 NSCLC patients underwent VATS lobectomy. The patients were selected on the basis of having clinical stage I disease on the chest CT and PET scan. The outcomes of 202 patients who underwent open lobectomy (OL group) for clinical stage I NSCLC were evaluated to compare their results with those of the patients who underwent VATS lobectomy (the VL group). Result: The number of females and the number of patients with adenocarcinoma and stage IA disease were greater in VL group (p<0.05). There was no operative mortality or major complications in the VL group. Conversion to thoracotomy was needed in 8 cases (6%), which was mostly due to bleeding. The chest tube indwelling time and the length of the postoperative hospital stay were significantly shorter in the VL group (p<0.001). The number of dissected lymph nodes and the size of tumor were significantly smaller in the VL group (p<0.001). For the pathologic stage I patients, there was no significant difference in the three-year survival rates between the two groups (p=0.15). Conclusion: VATS lobectomy is a safe procedure with low operative mortality and morbidity. VATS lobectomy is feasible for early stage NSCLC and it provides outcomes that are comparable to those for open lobectomy. Further long-term data are needed.

Studies on the Post-hatching Development of the Testis in Korean Native Chickens (한국 재래 닭 부화 후 고환 발달에 관한 연구)

  • Jang, B.G.;Tae, H.J.;Choi, C.H.;Park, Y.J.;Park, B.Y.;Park, S.Y.;Kang, H.S.;Kim, N.S.;Lee, Y.H.;Yang, H.H.;Ahn, D.C.;Kim, I.S.
    • Korean Journal of Poultry Science
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    • v.33 no.3
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    • pp.171-179
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    • 2006
  • Changes in the chicken testis from hatching to adulthood were studied in Korean native chickens of 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 21, 24, 28, 32, 44, 52 and 64 weeks (n=13 chickens per group) of age. The present study was to investigate in more detail the post-hatching development of testis in Korean native chickens. Testes of chickens were fixed by whole body perfusion using a fixative containing 2.5% glutaraldehyde in cacodylate buffer, processed and embedded in Epon-araldite. Using $1{\mu}m$ sections stained with methylene blue-azure II, qualitative and quantitative(stereological) morphological studies were performed. Sperm production was measured by routine technique. The average volume of a testis of 1 week old Korean native chickens was determined as 0.015 g and the parameter increased linearly from 1 week to 21 weeks days (28.9 g), and did not change from 21 weeks to 64 weeks. The volume density of the seminiferous tubules increased with age from 32.6% at week 1 to 92.89% at week 64. The volume density of the interstitium represents 67.4% of the testicular parenchyma at week 1. This proportion progressively diminished during development to reach a value of 7.11% at week 64. Total sperm production per testis increased significantly from 18 weeks to 28 weeks and remained unchanged. Sperm production per 1 g testis increased significantly from 18 weeks to 28 weeks, did not change significantly from 28 weeks to 52 weeks, and declined significantly at 64 weeks of age. The average diameter of the seminiferous tubules gradually increased with age from 1 week $(42.4{\mu}m)$ to 21 weeks $(412.8{\mu}m)$. The length of the seminiferous tubules was 0.34 m at 1 week, increased significantly in subsequent age groups and reached 72.2 m by weeks 64. The stage of germ cell development in seminiferous tubules was classified as 1) spermatogonia $(1\sim8\;weeks)$, 2) spermatogonia and spermatocytes $(10\sim12\;weeks)$, 3) spermatogonia, spermatocytes and round spermatids $(14\sim16\;weeks)$, and 4) speramatogonia, spermatocytes, spermatids and spermatozoa $(18\sim64\;weeks)$. These results clarified the pattern of changes in the testicular development in Korean native chickens from hatching to adulthood as 1) neonatal-prepubertal $(1\sim12\;weeks)$, 2) puberty$(14\sim18\;weeks)$, and adult$(21\sim64\;weeks)$.

Fragrance, Chemical Composition and Toxicity of the Essential Oil in Erect Bur-marigold (Bidens tripartita L.) (가막사리 (Bidens tripartita L.) 정유의 향취, 화학성분 및 세포독성)

  • Yun, Mi-Sun;Yeon, Bo-Ram;Cho, Hae-Me;Lee, Sa-Eun;Jhoo, Jin-Woo;Jung, Ji-Wook;Park, Yu-Hwa;Kim, Song-Mun
    • Korean Journal of Weed Science
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    • v.32 no.3
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    • pp.195-203
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    • 2012
  • The essential oil was extracted by steam distillation from the aerial part of erect bur-marigold (Bidens tripartita L.), one of the noxious weed in paddy field. The composition of the essential oil was analyzed by gas chromatography-mass spectrometry. The fragrance of the essential oil was green, herbal, oily, spicy. There were 42 constituents in the essential oil:17 hydrocarbons, 6 alcohols, 6 acetates, 5 N-containing compounds, 3 ethers, 3 ketones, 1 lactone and 1 S-containing compound. Major constituents were ${\alpha}$-phellandrene (22.50%), ${\alpha}$-pinene (22.21%), 2,4-dimethyl (2,5-dimethylphenyl) methyl ester benzoic acid (15.11%), limonene (10.66%), ${\beta}$-pinene (35.43%), and ${\beta}$-cubebene (5.27%). The $IC_{50}$ value in MTT assay using HaCaT keratinocyte cell line was 0.018%. However, attachment of patch with 0.1% of the erect bur-marigold essential oil for 24 hr did not show any skin toxicity. Overall results of this study suggest that the essential oil of erect bur-marigold could be used as a source for the development of perfumery industrial products.

Studies on Dry Matter Yield s, Chmical Composition And Net Energy Accumlation in Three Leading Temperate Grass Species III. Seasonal changes of chemical components under dfferent cutting managements (주요북방형 목초의 건물수량 , 화학성분 및 Net Energy 축적에 관한 연구 III. 예취관리에 화학성분의 계절적 변화)

  • 김정갑;양종성;한흥전
    • Journal of The Korean Society of Grassland and Forage Science
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    • v.6 no.3
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    • pp.157-163
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    • 1986
  • Synthesis and accumulation pattern of Weender components in orchardgrass (Dactylis glomerata L.) cv. Potomac and Baraula, perennial ryegrass (Lolium perenne L.) cv. Reveille and Semperweide and meadow fescue (Festuca pratensis Huds.) cv. Cosmos 11 and N.F.G. were studied under different growth environments and cutting managements. The field experiments were conducted as a split plot design with three cutting regimes of 6-7 cuts at grazing stage, 4-5 cuts at silage and 3 cuts at hay stage from 1975 to 1979 in Korea and West Germany. The results obtained are summarized as follows: 1. Air temperature, rainfalls and solar radiation were found to be an important meteorological factors influenced to synthesis and accumulation of Weender components. Under high temperature and strong solar radiation during summer season in Korea, accumulation of crude fiber and cell-wall constituents (NDF) in the plants, as average of all grass species and cutting regimes, were increased to about 30.1% and 48.7% from 27,9% and 42.9% in spring, respectively, while total nonstructural carbohydrates (TNC) were decreased to 1.52% in summer from 4.01% in spring. In West Germany, the concentration of Weeder components showed little seasonal variation. 2. Crude fiber and neutral detergent fiber (NDF) were shown higher concentration in orchardgrass than those of perennial ryegrass and meadow fescue, but N-free extractions and TNC as well as net energy value were less accumulated in orchardgrass. Orchardgrass contained lower net energy contents with 534 StE. 431 StE and 575 StE/kg for Suweon, Cheju and Freising, respectively, as compared with 624 StE (Suweon), 491 StE (Cheju) and 657 StE/kg (Freising) in meadow fescue.

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