• Title/Summary/Keyword: cell toxicity

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Suppressive Effects of Epigallocatechin Gallate Pretreatment on the Expression of Inflammatory Cytokines in RAW264.7 Cells Activated by Lipopolysaccharide (Lipopolysaccharide로 활성화된 RAW264.7세포에서 염증반응사이토카인 발현에 대한 Epigallocatechin gallate의 억제효능연구)

  • Seo, Eun Ji;Go, Jun;Kim, Ji Eun;Koh, Eun Kyoung;Song, Sung Hwa;Sung, Ji Eun;Park, Chan Kyu;Lee, Hyun Ah;Kim, Dong Seob;Son, Hong Joo;Lee, Cung Yeoul;Lee, Hee Seob;Hwang, Dae Youn
    • Journal of Life Science
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    • v.25 no.9
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    • pp.961-969
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    • 2015
  • Epigallocatechin gallate (EGCG), the main catechin in green tea, has been shown to have some beneficial effects against various human diseases, including diabetes, neurodegenerative disorders, cancer, cardiovascular disease and obesity. To investigate the mechanism of the suppressive effects of EGCG on inflammatory response in macrophages, alterations on the levels of nitric oxide (NO) regulatory factors and inflammatory cytokines were measured in lipopolysaccharide (LPS)-activated RAW264.7 cells. No significant toxicity was detected in RAW264.7 cells treated with 100–400 μM EGCG. Moreover, the optimal concentration of LPS was determined to be 1 μg/ml based on the results of cell viability assay, NO assay and IL-6 enzyme-linked immunsorbent assay (ELISA). Furthermore, NO levels decreased significantly by 68.2% in the 400 μM EGCG/LPS treated group, while the level of inducible nitric oxide synthase (iNOS) expression decreased by 12-17% in the 200 and 400 μM EGCG/LPS treated group. A significant decrease in transcription of pro-inflammatory cytokines (TNF- α and IL-1β) and anti-inflammatory cytokine (IL-10) was also detected in the EGCG/LPS treated group. However, IL-6 transcript and protein was maintained at a constant level when in the LPS treated group relative to the EGCG/LPS treated group. Overall, these results suggest that the differential regulation of inflammatory cytokines is an important factor influencing the suppressive effects of EGCG against LPS-activated inflammatory response in RAW264.7 cells.

The Effects of Onion Extracts on Mercury-Induced Toxicity and Lipid Peroxidation in Rat Hepatocyte Primary Culture (랫드 간세포 일차배양에서 양파 추출물이 수은에 의해 유도된 독성 및 지질과산화에 미치는 영향)

  • Rhim, Tae-Jin;Lim, Sang-Cheol
    • Korean Journal of Environmental Agriculture
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    • v.24 no.2
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    • pp.146-152
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    • 2005
  • The objective of present study was to investigate the effect of onion extracts on mercuryinduced cytotoxicity, lipid peroxidation and antioxidant enzyme activities in primary monolayer cultures of rat hepatocytes. Primary cultures of rat hepatocytes were incubated for 6 hr in the presence of various concentrations (0, 1, 5, 10, 30 or 50 ppm) of $HgCl_2$. Cytotoxicity and cell viability were determined by measuring glutamic oxaloacetic transaminase (GOT) activity, lactate dehydrogenase (LDH) activity and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) value. Lipid peroxidation w as evaluated using thiobarbituric acid reactive substances (TBARS) assay. Effects of onion extract on antioxidant system were determined by measuring catalase, glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rd) activities as well as DPPH free radical scavenging activity. $HgCl_2$ at the concentration of 10 ppm increased GOT activity and TBARS concentration but decreased %MTT reduction, whereas $HgCl_2$ at the concentration of 30 ppm increased LDH activity, representing that $HgCl_2$ caused cytotoxicity and lipid peroxidation in dose-dependent manner, $HgCl_2$ at the concentration of 30 ppm significantly decreased catalase, GSH-Px and GSH-Rd activities. When primary cultures of rat hepatocytes were incubated with various concentrations (0, 0.01, 0.05, 0.1 or 0.3 mg/ml) of onion extract for 6 hr in the presence of 30 ppm of $HgCl_2$, onion extracts at the concentration of 0.05 mg/ml decreased GOT activity, but increased %MTT reduction by 30 ppm of $HgCl_2$. $HgCl_2-induced$ LDH activity and TBARS concentration were decreased by onion extract at the concentration of 0.01 mg/ml. Taken together, onion extract prevented H$HgCl_2-induced$ hepatocyte injury and lipid peroxidation. Onion extracts at the concentration of 0.1 mg/ml almost or completely inhibited $HgCl_2-induced$ catalase and GSB-Px activities. GSH-Rd activity, however, was not affected by onion extract. Free radical scavengjing activity was increased as concentration of onion extract increased. Onion extract at the concentrion of 5 mg/ml possesed mote than 93% scavenging activity comparing to 100% radical scavenging activity by pyrogallol solution as a reference. These results demonstrate that onion extracts suppressed mercury-induced cytoctoxicity and lipid peroxidation by scavenging free radical and increasing catalase and GSH-Px activities.

Phytic Acid Protects the Formation of Colonic Aberrant Crypt Foci Induced by Azoxymethane in Male F344 Rats (랫드에서 azoxymethane으로 유도된 대장 전암병변에 대한 피티산의 방어 효과)

  • Hue, Jin-Joo;Lee, Yea-Eun;Lee, Ki-Nam;Nam, Sang-Yoon;Ahn, Byeong-Woo;Yun, Young-Won;Lee, Beom-Jun
    • Journal of Food Hygiene and Safety
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    • v.23 no.3
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    • pp.264-270
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    • 2008
  • Phytic acid(PA) (Inositol hexaphosphate, $IP_6$) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plants and mammalian cells. Recently PA has received much attention for its role in anticancer activity. In the present study, the preventive effects of PA on colon carcinogenesis were investigated. Six-week old Fisher 344 male rats were fed a AIN-93G purified diet and PA(0.5% or 2% PA in water) for 8 weeks. The animals received two ($1^{st}\;and\;2^{nd}$ week) injections of azoxymethane(AOM, 15 mg/kg b.w.) to induce colonic aberrant crypt foci(ACF). After sacrifice, the total numbers of aberrant crypts(AC) and ACF in colonic mucosa were examined after staining with methylene blue. Blood and serum were analyzed with a blood cell differential counter and an automatic serum analyzer. AOM induced the total numbers of $142.3{\pm}22.3$ ACF/colon and $336.6{\pm}55.1$ AC/colon. PA at the doses of 0.5 and 2% decreased the numbers of ACF and AC/colon in a dose-dependent manner. The numbers of ACF/colon and AC/colon by PA at the dose of 0.5% were $124.4{\pm}28.5\;and\;302.7{\pm}67.3$, respectively. PA at the dose of 2% significantly decreased the ACF and AC numbers to $109{\pm}18.1\;and\;254.8{\pm}50.6$, respectively(p<0.01). Especially, 2% PA significantly reduced the number of large ACF(${\geq}4$ AC/ACF) from $26.8{\pm}6.2$ ACF/colon to $15{\pm}6.7$ ACF/colon(p<0.01). Although some parameters in blood counts and serum chemistry were changed compared with the control, no specific toxicity was found. These findings suggest that phytic acid can be a chemopreventive agent for colon carcinogenesis resulting from inhibition of the development of ACF in the F344 rat.

The Results and Prognostic Factors of Postoperative Radiation Therapy in the Early Stages of Endometrial Cancer (초기 자궁내막암의 수술 후 방사선치료의 결과와 예후인자)

  • Lee, Kyung-Ja
    • Radiation Oncology Journal
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    • v.26 no.3
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    • pp.149-159
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    • 2008
  • Purpose: To evaluate the results and prognostic factors for postoperative adjuvant radiation therapy in patients at stages I and II of endometrial cancer. Materials and Methods: Between January 1991 and December 2006, 35 patients with FIGO stages I and II disease, who received adjuvant radiation therapy following surgery for endometrial cancer at Ewha Womans University Hospital, were enrolled in this study. A total of 17 patients received postoperative pelvic external beam radiation therapy; whereas, 12 patients received vaginal brachytherapy alone, and 6 patients received both pelvic radiation therapy and vaginal brachytherapy. Results: The median follow-up period for all patients was 54 months. The 5-yr overall survival and disease-free survival rates for all patients were 91.4% and 81.7%, respectively. The 5-yr overall survival rates for low-risk, intermediate-risk, and high-risk groups were 100%, 100% and 55.6%, respectively. In addition, the 5-yr disease-free survival rates were 100%, 70.0%, and 45.7%, respectively. Although no locoregional relapses were identified, distant metastases were observed in 5 patients (14%). The most common site of distant metastases was the lung, followed by bone, liver, adrenal gland, and peritoneum. A univariate analysis revealed a significant correlation between distant metastases and risk-group (p=0.018), pathology type (p=0.001), and grade (p=0.019). A multivariate analysis also revealed that distant metastases were correlated with pathology type (p=0.009). Papillary, serous and clear cell carcinoma cases demonstrated a poor patient survival rate compared to cases of endometrioid adenocarcinoma or adenosquamous carcinoma. The most common complication of pelvic external beam radiation therapy was enteritis (30%), followed by proctitis, leucopenia, and lymphedema. All these complications were of RTOG grades 1 and 2; no grades 3 and 4 were observed. Conclusion: For the low-risk and intermediate-risk groups (stages 1 and 2) endometrial cancer, pelvic control, and overall survival rate was free of severe toxicity when pelvic radiation therapy or vaginal brachytherapy was performed. In the high-risk group, pelvic control rate was excellent, but the survival rate was poor due to distant metastases, in spite of the pelvic radiation therapy. The combined modality of chemotherapy and radiation therapy is recommended for high-risk groups. For the intermediate-risk group, a prospective randomized study is required to compare the efficacy between whole pelvic radiation therapy and vaginal brachytherapy.

Anti-Inflammatory Effects of Extracts from Ligustrum ovalifolium H. Leaves on RAW264.7 Macrophages (RAW264.7 대식세포에서 왕쥐똥나무잎 추출물의 항염증 효과)

  • Kim, Yon-Suk;Lee, Seung-Jae;Hwang, Jin-Woo;Kim, Ee-Hwa;Park, Pyo-Jam;Jeong, Jae-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.9
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    • pp.1205-1210
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    • 2012
  • This study investigated the anti-inflammatory effects of Ligustrum ovalifolium H. (LOH) leaf extracts on RAW264.7 macrophages. Cell toxicity was determined by MTT assay. We evaluated the anti-inflammatory effects of LOH extracts by measuring nitric oxide (NO), reactive oxygen species (ROS), inducible NOS (iNOS) production, and cyclooxygenase-2 (COX-2) expression by Western blotting. LOH ethanolic extracts (0.05, 0.1, and 0.2 mg/mL) significantly suppressed LPS-stimulated production of NO. The intracellular ROS level also significantly decreased. LOH ethanolic extracts reduced the expression of iNOS and COX-2 proteins. The present results show that LOH ethanol extract has potent anti-inflammatory effects on RAW264.7 macrophages. These results also suggest that the anti-inflammatory effects of LOH extracts may be related to the inhibition of LPS-stimulated ROS and NO production. Therefore, ethanolic extracts of LOH leaves may be utilized as a good source of functional foods for protection against inflammatory diseases.

Outcome of patients with neuroblastoma aged less than 1 year at diagnosis (진단 시 1세 이하인 신경모세포종 환자의 치료성적)

  • Suh, Jung Min;Lee, Sang Goo;Yoo, Keon Hee;Sung, Ki Woong;Koo, Hong Hoe;Kim, Ju Youn;Cho, Eun Joo;Lee, Suk Koo;Kim, Jhingook;Lim, Do Hoon
    • Clinical and Experimental Pediatrics
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    • v.52 no.1
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    • pp.93-98
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    • 2009
  • Purpose : The purpose of this study was to evaluate the clinical characteristics and outcomes of patients with neuroblastoma aged less than 1 year. Methods : From January 1997 to December 2007, 41 patients aged less than 1 year were diagnosed with neuroblastoma. Patients were divided into 3 risk groups according to the stage of the disease and N-myc amplification. Low-risk patients underwent surgery with (stage 2) or without (stage 1) short-term chemotherapy. Intermediate-risk patients underwent chemotherapy and surgery with or without local radiation therapy. High-risk patients underwent chemotherapy, surgery, radiation therapy, and high-dose chemotherapy/autologous stem cell rescue (HDCT/ASCR). Results : While tumor relapse occurred in only 1 patient, 7 patients died of treatment-related toxicities. Causes of treatment- related death included infection during conventional chemotherapy in 5 patients and acute myocarditis during HDCT/ASCR in 2 patients. The overall 5-year survival (${\pm}$ standard error) and 5-year event-free survival (EFS) rates after diagnosis for all 41 patients were $82.8{\pm}5.9%$ and $80.0{\pm}$6.3%$, respectively, with a median follow-up of 58 (9-137) months. The 5-year EFS rates for low-risk, intermediate-risk, and high-risk patients were 100%, $68.4{\pm}10.8%$, and $66.7{\pm}19.3%$, respectively. Conclusion : Increased efforts to reduce infection-associated toxicity deaths during conventional chemotherapy are needed to further improve the survival of patients with neuroblastoma aged less than 1 year.

Toxic effects of antifouling agents (diuron and irgarol) on fertilization and normal embryogenesis rates in the sea urchin (Mesocentrotus nudus) (둥근성게(Mesocentrotus nudus)의 수정 및 배아 발생률에 미치는 신방오도료(Diuron, Irgarol)의 독성영향)

  • Hwang, Un-Ki;Lee, Ju-Wook;Park, Yun-Ho;Heo, Seung;Choi, Hoon
    • Korean Journal of Environmental Biology
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    • v.38 no.2
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    • pp.207-215
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    • 2020
  • Toxic assessment of antifouling agents (diuron and irgarol) was conducted using the fertilization and the normal embryogenesis rates of the sea urchin, Mesocentrotus nudus. Bioassessment began with male and female reproductive cell induction. White or cream-colored male gametes(sperm) and yellow or orange-colored female gametes (eggs) were acquired and fully washed, separately. Then, the fertilization and normal embryogenesis rates were measured after 10 min and 48 h of exposure to the toxicants, respectively. The fertilization and embryo development rates were greater than 90% in the control, validating the suitability of both endpoints. The normal embryogenesis rates were significantly decreased with increasing concentrations of diuron and irgarol, but no changes in the fertilization rates were observed in concentrations ranging from 0 to 40 mg L-1. The EC50 values of diuron and irgarol for the normal embryogenesis rates were 20.07 mg L-1 and 22.45 mg L-1, respectively. The no observed effect concentrations (NOEC) were <1.25 mg L-1 and the lowest observed effect concentrations (LOEC) were 1.25 mg L-1 and 2.5 mg L-1, respectively. From these results, concentrations of diuron and irgarol over 1.25 mg L-1 and 2.5 mg L-1, respectively, can be considered to have toxic effects on invertebrates, including M. nudus. The ecotoxicological bioassay in this study using the noted fertilization and normal embryogenesis rates of M. nudus can be used as baseline data for the continued establishment of environmental quality standards for the effects of antifouling agents(especially diuron and irgarol) in a marine environment.

A STUDY OF NI-RESISTANT BACTERIA ON THE RESTORED STAINLESS STEEL CROWN (기성금관 수복어린이에서의 니켈내성균에 관한 연구)

  • Chung, Sat-Byul;Lee, Keung-Ho
    • Journal of the korean academy of Pediatric Dentistry
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    • v.27 no.2
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    • pp.274-282
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    • 2000
  • Stainless steel crowns are widely used for restoration for primary molars. The material used for the crowns is an alloy of $70\sim80%$ nickel and $5\sim15%$ chromium. Nickel has been known to cause allergic reaction, cancer and cell toxicity. Little is known about nickel with respect to the relationship between Ni-contained SS crown and graining of Ni-resistance in oral microorganisms. The purpose of this study is to examine whether use of Ni-contained SS crown leads to occurrence of Ni-resistant microorganism, especially enterococci. The gingival crevicular fluid of two different groups was taken. Experimental group included patients wearing SS crown, and control group comprised individuals without SS crown. The samples were plated in BHI agar, BHI agar supplemented with nickel chloride at the concentration of 3mM and bile esculin azide (BEA) agar. The cultured enterococci on BEA agar medium were tested their Ni-resistance in nickel-containing media increasing concentrations from 3mM to 50mM. The results were as follows: 1. In experimental group, a total of 507,350 strains were isolated on BHI agar, of which 53,864(10.62%) strains were found to be resistant to 3mM nickel. In control group, of 414,590 isolates on BHI agar, 37,523 isolates were resistant to 3mM nickel. 2. A total of 95 enterococci were isolated on BEA agar in experimental group, while 20 were isolated in control group. of the enterococci, 68 and 12 isolates were found to be nickel-resistant in experimental and control group, respectively. 3. Of 68 nickel-resistant isolates in experimental group, one survived 50mM nickel. In contrast, none of the isolates in control group was observed to grow at the concentrations over 30mM nickel.

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The Anti-inflammatory Effect of Skipjack Tuna (Katsuwonus pelamis) Oil in LPS-induced RAW 264.7 Cells and Mouse Models (LPS 유도 RAW 264.7 세포와 마우스 모델에서 참치(Katsuwonus pelamis) 유의 항염증 효과)

  • Kang, Bo-Kyeong;Kim, Min-Ji;Kim, Koth-Bong-Woo-Ri;Ahn, Na-Kyung;Choi, Yeon-Uk;Bark, Si-Woo;Pak, Won-Min;Kim, Bo-Ram;Park, Ji-Hye;Bae, Nan-Young;Ahn, Dong-Hyun
    • Microbiology and Biotechnology Letters
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    • v.43 no.1
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    • pp.45-55
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    • 2015
  • This study was carried out to demonstrate the anti-inflammatory effect of tuna oil (TO) using LPS-induced inflammation responses and mouse models. First, nitric oxide (NO) and pro-inflammatory cytokines levels were suppressed up to 50% with increasing concentrations of TO without causing any cytotoxicity. Also, the expression of a variety of proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB), was suppressed in a dosedependent manner by treatment with TO. Furthermore, TO also inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs), including c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 protein kinase (p38). Moreover, in in vivo testing the formation of ear edema was reduced at the highest dose tested compared to that in the control, and a reduction of ear thickness and the number of mast cells was observed in histological analysis. In acute toxicity test, no mortalities occurred in mice administrated 5,000 mg/kg body weight of TO over a two-week observation period. Our results suggest that TO has a considerable anti-inflammatory property through the suppression of inflammatory mediator productions and that it could prove to be useful as a potential anti-inflammatory therapeutic material.

Comparison of Amphotericin B and Itraconazole as Empirical Antifungal Therapy in Children with Acute Leukemia with Neutropenic Fever (발열을 동반한 호중구감소 상태의 급성백혈병 환아에서 경험적 항진균제로 투여한 Amphotericin B와 Itraconazole의 효과와 이상 반응 비교)

  • Lee, Sang-Yun;Park, Jong-Sun;Kim, Sun-Young;Yang, Keum-Jin;Park, Kyung-Deok;Kim, Hack-Ki
    • Pediatric Infection and Vaccine
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    • v.12 no.1
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    • pp.75-85
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    • 2005
  • Purpose : Fungal infection is one of the important causes of morbidity and mortality in patients with hematologic malignancies. Amphotericin B(ABV) and itraconazole(ITZA) have been used as the standard empirical antifungal therapy in neutropenic patients with acute leukemia who have persistent fever that does not respond to antibiotic therapy. ABV is an antifungal drug associated with side effects such as fever and chills, symptoms which may be mediated by pro-inflammatory cytokines such as interleukin-$1{\beta}$(IL-$1{\beta}$) and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$). We assessed modulation of these pro-inflammatory cytokines as well as the anti-inflammatory cytokines(IL-4, IL-1Ra) by ABV and ITZA. Methods : From March 2004 to February 2005, a total of 30 episodes from acute leukemia patients with febrile neutropenia were analyzed for this study. They were randomly allocated to receive intravenous ABV or ITZA for 14 days. Clinical responses were evaluated at the completion of therapy, and cytokine IL-$1{\beta}$, TNF-${\alpha}$, IL-4, and IL-1Ra were measured for determination to know the correlation between two antifungal agents and inflammatory cytokines. Results : Empirical antifungal agents were given to 37 patients(ABV 20, ITZA 17), and 30 patients(ABV 15, ITZA 15) were evaluable for efficacy. White blood cell and absolute neutrophil count in the group treated with ITZA increased early days of treatment, so the duration of neutropenia in ITZA group is shorter. Serum creatinine level is lower in ITZA group than in ABV group but this is not statistically significant. There was no significant difference in response rate between two groups. The IL-$1{\beta}$ was increased in ABV treatment group and the ratio of IL-1Ra/IL-$1{\beta}$ is markedly decreased in ABV treatment group while increased in ITZA group. Conclusion : ITZA and ABV have at least equivalent efficacy as empirical antifungal therapy in neutropenic children with acute leukemia. However ITZA is associated with significantly less toxicity in clinical and molecular aspects.

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