• Title/Summary/Keyword: Reduction of human exposure

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Transfected HepG2 Cells for Evaluation of Catechin Effects on Alcohol-Induced CYP2E1 Cytotoxicity

  • LEE YOO-HYUN;HO JIN-NYOUNG;DONG MI-SOOK;PARK CHANG-HWAN;KIM HYE-KYUNG;HONG BUMSHIK;SHIN DONG-HOON;CHO HONG-YON
    • Journal of Microbiology and Biotechnology
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    • v.15 no.6
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    • pp.1310-1316
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    • 2005
  • To evaluate the toxicological properties of human cytochrome P450 2E1 (CYP2E1) induced by ethanol and possible protective effects of various green tea catechins on alcohol-induced toxicity, transfected HepG2 cells that stably and constitutively express human CYP2E1 were established using the recombinant retroviral expression vector. Exposure of the CYP2E1-expressing HepG2 cells to high concentration of ethanol (200 mM) for 5 days resulted in a more than $50\%$ increase of cytotoxicity, assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, lactate dehydrogenase (LDH) release, and reactive oxygen species (ROS) production, and loss of normal morphology, in comparison with HepG2 cells containing control vector. Treatment of the cells with various catechins increased cell viability by more than 2-fold. (-)-Epicatechin gallate and(-)-catechin gallate at the lowest concentration ($5\;{\mu}M$) attenuated cell death induced CYP2E1 by $60-65\%$. Therefore, the results showed that the catechins, including epimerized catechins, have strong protective effects against alcohol-induced CYP2E1 toxicity, and it is correlated with antioxidant effect.

The therapeutic effects of WSY-0702 on benign prostatic hyperplasia in RWPE-1

  • Oh, Hyun-A;Kwon, Eun Bi;Hwang, Yun Gyeong;Park, Soon Eung;Mok, Ji Ye;Hwang, Sung Yeoun
    • CELLMED
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    • v.7 no.2
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    • pp.8.1-8.7
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    • 2017
  • Benign prostatic hyperplasia (BPH) is one of the major diseases of the urinary system in older men. WSY-0702 is the extracted from the traditional medicinal plant; Seoritae, and it has effects of anti-obesity, chronic cervical pain, and anti-oxidant. The present study aimed to investigate the therapeutic potential of WSY-0702 in the prevention and treatment of BPH. Several parameters including inflammatory mediators, hormones, and oxidative stress (OS) have been considered to play a role in the development of BPH. Prostate tissue damage and OS may lead to compensatory cellular proliferation with resulting hyperplastic growth. An in vitro study showed that proliferation inhibited the human prostate epithelial cell line RWPE-1 in a dose-dependent manner. In cell line, the cell cycle at the G2/M and G0/G1 phase and downregulated the expression of CyclineB1 (CCNB1) and CyclineD1 (CCND1). In addition, we measured the $H_2O_2$-induced OS damage using RWPE-1 cells. We examined the relative expression of protein involved in the regulation of prostate apoptosis: transforming growth factor (TGF)-${\beta}$, a negative growth factor able to induced prostate apoptosis under physiological conditions. These results suggest that WSY-0702 that can inhibit the growth of prostate epithelial cell by a mechanism that may involve arresting the cell cycle and downregulating CCNB1 and CCND1 expression. In addition, WSY-0702 exposure resulted in significant protective effects in $H_2O_2$-stressed PWPE-1 cells by reduction in TGF-${\beta}$ levels.

Realization of High Impedance Surface Characteristics Using a Periodically Transformed Artificial Magnetic Conductor Structure and Reduction Technique of Specific Absorption Rate

  • Lee, Seungwoo;Rhee, Seung-Yeop;Kim, Pan-Yeol;Kim, Nam
    • Journal of electromagnetic engineering and science
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    • v.13 no.2
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    • pp.113-119
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    • 2013
  • We developed a transformed, symmetrical, mushroom-like surface without via holes in cells focused on a 2.4-GHz WLAN band. Each slot in the novel type structure plays a key role in modeling at the desired frequencies. The designed artificial magnetic conductor (AMC) has several advantages, including a small size, a wider bandwidth, a short reflecting distance to the antenna, and easy fabrication because there are no via holes. Overall dimensions of the AMC cell are 21 mm $(Width){\times}21mm$ $(Height){\times}2.6mm$ (Thickness), and the bandwidth is about three times wider (11.7%) compared to that of a conventional AMC (4.0%). For evaluating the performance of the proposed structure, a reflector, which periodically consists of the designed AMC cells, was developed. The antenna with the investigated AMC reflector not only works within a quarter of the wavelength because of the extremely high wave impedance generated by the AMC cells on the surface of the structure but also reduces the specific absorption rate (SAR). Electromagnetic field (EMF) exposure to a human phantom was analyzed by applying the designed reflector to the 2.4-GHz dipole antenna in a tablet PC. The calculated peak SAR averaged over 1 g was 0.125 W/kg when the input power was 1 W and the antenna was located at 20 cm from the human phantom. However, the SAR value was only 0.002 W/kg (i.e., 98.4% blocked) when the designed reflector was inserted in front of the antenna.

Over-expression of JunB inhibits mitochondrial stress and cytotoxicity in human lymphoma cells exposed to chronic oxidative stress

  • Son, Young-Ok;Heo, Jung-Sun;Kim, Tae-Geum;Jeon, Young-Mi;Kim, Jong-Ghee;Lee, Jeong-Chae
    • BMB Reports
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    • v.43 no.1
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    • pp.57-61
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    • 2010
  • Activator protein-1 can induce either cell survival or death, which is controlled by opposing effects of different Jun members. It is generally accepted that c-Jun is pro-apoptotic, but that JunD is anti-apoptotic in stress-exposed cells. Additionally, although there are reports suggesting that JunB plays a protective role, its role in stress-induced apoptosis remains unclear. Here, we investigated the role of JunB in $H_2O_2$-induced cell death using cells that over-expressed the protein or were transfected with si-JunB. Inhibition of JunB expression accelerated $H_2O_2$-mediated loss of mitochondrial membrane potential (MMP) and cytotoxicity. Conversely, over-expression of JunB protein led to significant inhibition of the MMP loss and cell death. The increase in JunB expression also attenuated nuclear relocation of apoptosis-inducing factor and mitochondrial Bcl-2 reduction that occurred following $H_2O_2$ exposure. These results suggest that JunB can signal survival against oxidant-mediated cell death by suppressing mitochondrial stress.

Comparative study of two collagen membranes for guided tissue regeneration therapy in periodontal intrabony defects: a randomized clinical trial

  • Chung, Young-Mi;Lee, Jue-Yeon;Jeong, Seong-Nyum
    • Journal of Periodontal and Implant Science
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    • v.44 no.4
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    • pp.194-200
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    • 2014
  • Purpose: The purpose of this study was to assess and compare the clinical and radiographic outcomes of guided tissue regeneration therapy for human periodontal intrabony defects using two different collagen membranes: a porous nonchemical cross-linking collagen membrane (NC) and a bilayer collagen membrane (BC). Methods: Thirty subjects were randomly assigned and divided into the following 3 groups: a test group (NC+BM), in which a NC was used with xenograft bone mineral (BM), a positive control group (BC+BM), in which a BC was used with xenograft BM, and a negative control group (BM), in which only xenograft BM was used. The following clinical measurements were taken at baseline and 3 months after surgery: plaque index, gingival index, probing pocket depth, gingival recession, and clinical attachment level. Radiographic analysis was performed at baseline, 1 week and 3 months after surgery. Results: Membrane exposure was not observed in any cases. Significant probing depth reduction, attachment-level gain and bone fill were observed for both test and control groups compared to baseline at 3 months after surgery (P<0.05). However, there were no statistically significant differences in clinical improvement and radiographic bone fill between treatment protocols (P>0.05). Conclusions: Within the limitations of this study, the results suggest that both NC and BC were comparable in terms of clinical and radiographic outcomes for the treatment of periodontal intrabony defects in human subjects.

A Study on the Hazardousness and the TLV in Working Environments of Benzine (벤진의 유해 위험성과 작업환경 노출기준 연구)

  • Kim, Hyeon-Yeong;Lee, Sung-Bae;Han, Jung-Hee;Shin, Jea-Hoon
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.16 no.3
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    • pp.233-244
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    • 2006
  • Of many volatile organic detergents for metals, benzine(CAS No. 8030-30-6), of which the toxicity has not yet been proven, has been used as an alternative of the halide compounds in the consideration of toxic effects, global warming and the destruction of ozone layer. In order to evaluate the effects of the benzine on human body by investigating the subchronic inhalation toxicity, to obtain the basic data for establishing the criteria of exposure in working environments and to classify the hazardousness in compliance with the Industrial Safety and Health Act by evaluating the hazardousness, repeated inhalation exposure test was carried with SD rats. The rats were grouped by 10 females and males each. The repetitive inhalation exposures were carried out at 4 levels of concentration of 0 ppm, 60 ppm, 300 ppm, and 1,500 ppm, for 6 hours a day, 5 days a week, for 13 weeks. The results are described hereunder. 1. No death of the animals of the exposed and controlled groups in the test period. Not any specific clinical symptoms, change in feed intake quantity, abnormality in eye test, or change in activity were observed. 2. In the 300 ppm and 1,500 ppm groups, weight reduction in the female groups and weight increase of liver and kidney in the male groups compared with control group were observed with statistical significance(p<0.05). 3. In the blood test, the HCT increased in the male 300 ppm group and the number of hematocyte increased, MCV and MCH decreased in the male 1,500 ppm group. In the female 1,500 ppm group, the HB decreased and the distribution width of the hematocyte particle size increased. In the blood biochemistry test, the TP in the male 1,500 ppm group and the LDH in the female 1,500 ppm group were increased with statistical significance(p<0.05). 4. Under the test conditions of the present study with SD rats, the NOEL was evaluated to be from 60 ppm to 300 ppm for both male and female groups. By extrapolation, the NOEL for human who work 8 hours a day was evaluated to be from 128 ppm to 640 ppm 5. Since the NOEL evaluated in this study do not exceed 60ppm(0.184 mg/L) the test material does not belong to the classification of the hazardous substance "NOEL${\leq}$0.5mg/L/6hr/90day(rat), for continuous inhalation of 6hours a day for 90 days" nor to the basic hazardous chemical substance class 1(0.2 mg/L/6hr/90day(rat) defined by the GHS which is a criteria of classification and identification of chemical compounds. However, considering the boiling point($30-204^{\circ}C$), flashing point($-40^{\circ}C$), vapor pressure(40 mmHg), and the inflammable range(1.0 - 6.0 %), sufficient care should be taken for handling in the safety aspects including fire or explosion.

Capsaicin Intake Estimated by Urinary Metabolites as Biomarkers (뇨중 대사체 정량에 의한 capsaicinoid의 생화학적 섭취지표 개발 연구)

  • Choo, Yeon-Soo;Kwon, Hoon-Jeong
    • Korean Journal of Food Science and Technology
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    • v.33 no.6
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    • pp.784-788
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    • 2001
  • Reliable data on the exposure of capsaicin, which evokes hot sensation in hot red pepper, are important prerequisites for studying biological functions of capsaicin in human body since its roles are controversial according to animal and epidemiological studies. To get accurate data, the use of urinary biomarkers was considered as a measure of internal exposure of capsaicin. After 2-day-capsaicin depletion five to six women in their 20's were instructed to eat 60 or 80 g/day hot red pepper soybean paste as a capsaicin source with meal which did not contain capsaicinoid, and to collect their urine separately. HPLC conditions were set to detect capsaicinoid and urinary metabolites at the same time. Most of capsaicinoid were excreted in the form of 4-hydroxy-3-methoxybenzoic acid in three subjects at the highest dose. This result suggests the oxidation of the 4-hydroxy3-methoxybenzaldehyde, the hydrolysis product of capsaicin, is the major metabolic pathway in the human body, whereas the reduction of the aldehyde is the major route in rats. However, neither any metabolite nor the parent compound was ever shown in two of the subjects reflecting large individual differences of capsaicin absorption and/or biotransformation.

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Selection of Vaccinia Virus-Neutralizing Antibody from a Phage-Display Human-Antibody Library

  • Shin, Yong Won;Chang, Ki-Hwan;Hong, Gwang-Won;Yeo, Sang-Gu;Jee, Youngmee;Kim, Jong-Hyun;Oh, Myoung-don;Cho, Dong-Hyung;Kim, Se-Ho
    • Journal of Microbiology and Biotechnology
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    • v.29 no.4
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    • pp.651-657
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    • 2019
  • Although smallpox was eradicated in 1980, it is still considered a potential agent of biowarfare and bioterrorism. Smallpox has the potential for high mortality rates along with a major public health impact, eventually causing public panic and social disruption. Passive administration of neutralizing monoclonal antibodies (mAbs) is an effective intervention for various adverse reactions caused by vaccination and the unpredictable nature of emerging and bioterrorist-related infections. Currently, vaccinia immune globulin (VIG) is manufactured from vaccinia vaccine-boosted plasma; however, this production method is not ideal because of its limited availability, low specific activity, and risk of contamination with blood-borne infectious agents. To overcome the limitations of VIG production from human plasma, we isolated two human single-chain variable fragments (scFvs), (SC34 and SC212), bound to vaccinia virus (VACV), from a scFv phage library constructed from the B cells of VACV vaccine-boosted volunteers. The scFvs were converted to human IgG1 (VC34 and VC212). These two anti-VACV mAbs were produced in Chinese Hamster Ovary (CHO) DG44 cells. The binding affinities of VC34 and VC212 were estimated by competition ELISA to $IC_{50}$ values of $2{\mu}g/ml$ (13.33 nM) and $22{\mu}g/ml$ (146.67 nM), respectively. Only the VC212 mAb was proven to neutralize the VACV, as evidenced by the plaque reduction neutralization test (PRNT) result with a $PRNT_{50}$ of ~0.16 mg/ml (${\sim}1.07{\mu}M$). This VC212 could serve as a valuable starting material for further development of VACV-neutralizing human immunoglobulin for a prophylactic measure against post-vaccination complications and for post-exposure treatment against smallpox.

Growth Inhibition of Human Uterine Leiomyoma Cells Using Haeohyul-tang (하어혈탕(下瘀血湯)이 1차배양된 인체자궁근종세포(人體子宮筋腫細胞)에 미치는 영향)

  • Kim, Han-Kyun;Zhao, Rong-Jie;Jo, Mi-Jeong;Choi, Sun-Mi;Park, Sook-Jahr;Kim, Mi-Ryeo;Kwon, Young-Kyu;Kim, Sang-Chan
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.1
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    • pp.158-164
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    • 2007
  • Uterine leiomyoma is the most common tumor in the female genital tract. Although the tumor is benign, it is a matter of paramount importance since it often causes profuse menstrual bleeding, pressure symptoms and infertility. Nevertheless, the etiology and pathophysiology of this abnormality remain poorly understood. The traditional definitive treatment for uterine leiomyomas is hysterectomy and, even today, symptomatic leiomyomas are the leading cause of hysterectomy in Korea. Clearly, the development of a safe, effective, and nonsurgical method of treatment for leiomyoma would be of great benefit to many women. This study demonstrated growth inhibition of uterine leiomyoma cells using Haeohyultang (HT). When human leiomyoma cells were treated with Haeohyultang, cells showed dose-dependent growth inhibitory effect. Cell growth was inhibited by over 40% as determined by both cell counts and MTS assay. Reduction of cellular viability as a consequence of exposure to Haeohyultang resulted from induction of apoptosis, as assessed by DNA fragmentation, PARP cleavage, caspase 9 and caspase 3 assay. Flow cytometry analysis with uterine leiomyoma cells demonstrated sub G1 cell cycle arrest after treatment with drug Haeohyultang. But, the expression levels of p27 and p21 were not changed in Haeohyultang treated cells compared with control. However, the expression levels of clAP1 were reduced by Haeohyultang compared with control. This reduction of clAP1 data means activation of the caspase family, and then induction of PARP cleavage and apoptosis. These results suggest that Haeohyultang may be potential therapeutic approach in the clinical management of uterine leiomyoma.

Anti-cancer effect of glabridin by reduction of extracellular vesicles secretion in MDA-MB-231 human breast cancer cells (유방암세포에서 세포외 소포체 분비 감소를 통한 glabridin의 항암효과)

  • Choi, Sang-Hun;Hwang, Jin-Hyeon;Baek, Moon-Chang;Cho, Young-Eun
    • Journal of Nutrition and Health
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    • v.55 no.2
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    • pp.240-249
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    • 2022
  • Purpose: Glabridin (GD) is a bio-available isoflavane isolated from the root extract of licorice (Glycyrrhiza glabra L.). It exhibits a variety of pharmacological activities such as anti-inflammatory and anti-oxidant activities. However, extracellular vesicles (EVs) secretion and the anti-cancer mechanism of action remains largely unknown. The present study investigates the anticancer effects of GD by determining the inhibition of EVs secretion in the human breast cancer cell line, MDA-MB-231. Methods: Cell viability, reactive oxygen species (ROS) production, migration, invasion rate, and vascular endothelial growth factor (VEGF) concentration were assessed in MDA-MB-231 cells treated with increasing concentrations of GD (0.1, 1, 5, 10, 20 µM). Subsequently, EV secretion and exosomal DEL-1 protein expression were evaluated to determine the anticancer effects of GD. Results: The results showed that GD significantly inhibited the cell proliferation of MDA-MB-231 cells in a dose- or time-dependent manner. Also, ROS production and apoptosis marker protein cleaved caspase-3 were significantly increased in GD-treated MDA-MB-231, compared to control. Furthermore, GD exposure resulted in significantly decreased not only migration and invasion rates but also the VEGF concentration, thereby contributing to a reduction in angiogenesis. Interestingly, the concentration and number of EVs as well as EV marker proteins, such as CD63 and TSG101, were decreased in GD-treated MDA-MB-231 cells. Markedly, extracellular matrix protein DEL-1 as angiogenesis factor was decreased in EVs from GD-treated MDA-MB-231 cells. Conclusion: This study identifies that the anti-cancer molecular mechanism of GD is exerted via inhibition of angiogenesis and EVs secretion, indicating the potential of GD as a chemotherapeutic agent for breast cancer.