• 생명과학회지
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• 제32권3호
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• pp.210-221
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• 2022

비스테로이드소염제(NSAID)와 γ-secretase 저해제(DAPT) 또는 SIRT1저해제(MHY2245)의 병용 효과를 인간 대장암(KM12) 및 간암(SNU475) 세포를 대상으로 조사한 결과, celecoxib (CCB) 및 2, 5-dimethyl celecoxib (DMC)를 포함하는 NSAID는 DAPT 또는 MHY2245와의 병용에 의하여 COX-2활성과 상관없이 NSAID의 암세포 증식 억제능이 현저히 증강되었다. DAPT와 MHY2245는 p62단백질 감소와 동시에 Notch1, CD44, CD133, octamer- binding transcription factor 4 (Oct4) 등의 다수의 종양 줄기세포 표지자 및 NICD1 발현 양을 감소시켰지만, activating transcription factor 4 (ATF4) 발현은 증강시켰다. 또한 NSAID 단독처리 보다 NSAID/DAPT 및 NSAID/MHY2245 병용 처리에 의하여 오토파지가 촉진되므로서 종양 줄기세포 표지자의 발현 및 단백질양의 감소가 가속화되고, 이에 따라 PARP 활성화 및 세포사멸이 현저히 증강 되었다. 결론적으로 NSAID/DAPT 및 NSAID/MHY2245의 병용 투여는 종양 줄기세포 표지자를 발현하는 인간 암세포의 증식 억제 및 제거에 효과적인 처리방법으로, 임상에 적용시킬 수 있는 학문적 근거로서 제공 될 수 있다.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2004년도 학술대회지
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• pp.1-20
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• 2004

Polychlorinated biphenyls (PCBs), one a group of persistent and widespread environmental pollutants, have been considered to be involved in immunotoxicity, carcinogenesis, and apoptosis. However, the toxic effects and physical properties of a PCB congener are dependent on the structure. In the present study, we investigate the toxic effects and action mechanisms of PCBs In cells. Among the various congeners tested, 2,2',4,6,6'-PeCB-pentachlorobiphenyl (PeCB), a highly ortho-substituted congener having negligible binding affinity for aryl hydrocarbon receptor (AhR), caused the most potent toxicity and specific effects in several cell types. 2,2',4,6,6'-PeCB induced apoptotic cell death of human monocytic cells, suggesting that PCB-induced apoptosis may be linked to immunotoxicity. In addition, 2,2',4,6,6'-PeCB induced mitotic arrest by interfering with mitotic spindle assembly in NIH3T3 fibroblasts, followed by genetic instability which triggers p53 activation. Which suggests that 2,2',4,6,6'-PeCB may be involved in cancer development by causing genetic instability through mitotic spindle damage. On the other hand, 2,2',4,6,6'-PeCB increased cyclooxygenase-2 (COX-2) involved in cell survival through ERK1/2 MAPK and p53 in Rat-1 fibroblasts and mouse embryonic fibroblasts, triggering compensatory mechanism for abating its toxicity. Taken together, these results demonstrate that PCB congeners of different structure have distinct mechanism of action and 2,2',4,6,6'-PeCB causes several toxicity as well as compensatory mechanism in cells.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2018년도 추계학술대회
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• pp.98-98
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• 2018

In this study, we evaluated the anti-inflammatory effect of extracts of leaves (ST-L) and branches (ST-B) from Sageretia theezans in LPS-stimulated RAW264.7 cells. ST-L and ST-B significantly inhibited the production of the pro-inflammatory mediators such as NO, iNOS, COX-2, $IL-1{\beta}$ and IL-6 in LPS-stimulated RAW264.7 cells. ST-L and ST-B blocked LPS-induced degradation of $I{\kappa}B-{\alpha}$ and nuclear accumulation of p65, which resulted to the inhibition of $NF-{\kappa}B$ activation in RAW264.7 cells. ST-L and ST-B also attenuated the phosphorylation of ERK1/2, p38 and JNK in LPS-stimulated RAW264.7 cells. In addition, ST-L and ST-B increased HO-1 expression in RAW264.7 cells, and the inhibition of HO-1 by ZnPP reduced the inhibitory effect of ST-L and ST-B against LPS-induced NO production in RAW264.7 cells. Inhibition of p38 activation and ROS elimination attenuated HO-1 expression by ST-L and ST-B, and ROS elimination inhibited p38 activation induced by ST-L and ST-B. ST-L and ST-B dramatically induced nuclear accumulation of Nrf2, but this was significantly reversed by the inhibition of p38 activation and ROS elimination. Collectively, our results suggest that ST-L and ST-B exerts potential anti-inflammatory activity by suppressing $NF-{\kappa}B$ and MAPK signaling activation, and activating HO-1 expression through the nuclear accumulation of Nrf2 via ROS-dependent p38 activation. These findings suggest that ST-L and ST-B may have great potential for the development of anti-inflammatory drug to treat acute and chronic inflammatory disorders.

• Journal of Preventive Medicine and Public Health
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• 제38권2호
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• pp.203-207
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• 2005

Objectives: Recently, the American Diabetes Association (ADA) redefined the criteria of prediabetes, which has lowered the diagnostic level of fasting plasma glucose (FPG) from 110 to 125 mg/dl, down to levels between 100 to 125mg/dl. The purpose of this study was to determine the predictive cutoff level of FPG as a risk for the development of diabetes mellitus in Korean men. Methods: A retrospective cohort study was conducted on 11,423 (64.5%) out of 17,696 males $\leq$30 years of age, and who met the FPG of $\leq$125 mg/dl and hemoglobin A1c of $\leq$ 6.4% criteria, without a history of diabetes, and who were enrolled at the screening center of a certain university hospital between January and December 1999. The subjects were followed from January 1999 to December 2002 (mean follow-up duration; 2.3(${\pm}0.7$) years). They were classified as normal (FPG <100mg/dl), high glucose (FPG $\geq$100mg/dl and <110mg/dl) and impaired fasting glucose (FPG $\geq$110mg/dl and $\leq$125mg/dl) on the basis of their fasting plasma glucose level measured in 1999. We compared the incidence of diabetes between the 3 groups by performing Cox proportional hazards model and used receiver operating characteristic analyses of the FPG level, in order to estimate the optimal cut-off values as predictors of incident diabetes. Results: At the baseline, most of the study subjects were in age in their 30s to 40s (mean age, 41.8(${\pm}7.1$) year). The incidence of diabetes mellitus in this study was 1.19 per 1,000 person-years (95% CI=0.68-1.79), which was much lower than the results of a community-based study that was 5.01 per 1,000 person-years. The relative risks of incident diabetes in the high glucose and impaired fasting glucose groups, compared with the normal glucose group, were 10.3 (95% CI=2.58-41.2) and 95.2 (95% CI= 29.3-309.1), respectively. After adjustment for age, body mass index, and log triglyceride, a FPG greater than 100mg/dl remained significant predictors of incident diabetes. Using the receiver operating characteristic (ROC) curve, the optimal cutoff level of FPG as a predictor of incident diabetes was 97.5 mg/dl, with a sensitivity and a specificity of 81.0% and 86.0%, respectively. Conclusion: These results suggest that lowering the criteria of impaired fasting glucose is needed in Korean male adults. Future studies on community-based populations, including women, will be required to determine the optimal cutoff level of FPG as a predictor of incident diabetes.

• Journal of Chest Surgery
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• 제52권4호
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• pp.221-226
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• 2019

Background: Accurate mediastinal lymph node staging is vital for the optimal therapy and prognostication of patients with lung cancer. This study aimed to determine the preoperative risk factors for pN2 disease, as well as its incidence and long-term outcomes, in patients with clinical N0-1 non-small cell lung cancer. Methods: We retrospectively analyzed patients who were treated surgically for primary non-small cell lung cancer from November 2005 to December 2014. Patients staged as clinical N0-1 via chest computed tomography (CT) and positron emission tomography (PET)-CT were divided into two groups (pN0-1 and pN2) and compared. Results: In a univariate analysis, the significant preoperative risk factors for pN2 included a large tumor size (p=0.083), high maximum standard uptake value on PET (p<0.001), and central location of the tumor (p<0.001). In a multivariate analysis, central location of the tumor (p<0.001) remained a significant preoperative risk factor for pN2 status. The 5-year overall survival rates were 75% and 22.9% in the pN0-1 and pN2 groups, respectively, and 50% and 78.2% in the patients with centrally located and peripherally located tumors, respectively. In a Cox proportional hazard model, central location of the tumor increased the risk of death by 3.4-fold (p<0.001). Conclusion: More invasive procedures should be considered when preoperative risk factors are identified in order to improve the efficacy of diagnostic and therapeutic plans and, consequently, the patient's prognosis.

• 한국식품영양과학회지
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• 제44권10호
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• pp.1439-1449
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• 2015

우리나라에서는 전통적으로 복숭아꽃을 차로 마셔왔으며 피부 부스럼 등의 치료에 이용하였다는 기록이 있어 복숭아꽃 추출물이 산화적 스트레스와 염증반응을 억제시키는 효과가 있는지를 본 연구에서 확인하고자 하였다. 복숭아꽃을 건조시킨 다음 에탄올 추출 농축액(EtOH)을 얻었고, 이로부터 다시 hexane(Hx), dichloromethane(DM), ethyl acetate(EA), n-butanol(BtOH) 및 water(DW) 순으로 순차적 용매 분획을 시행하여 획득한 각 농축액에서 총 페놀화합물 함량, 플라보노이드 함량, DPPH 라디칼과 ABTS 라디칼 소거능을 측정하였고, LPS를 처리한 RAW 264.7 대식세포에서 이들 추출물들이 NO, PGE2, IL-6, TNF-${\alpha}$ 생성에 미치는 영향을 측정하였다. 그 결과 총 페놀화합물 함량과 플라보노이드 함량은 EA 분획(394.6 mg TA/g, 253.7 mg RT/g)이 가장 높았고, 그다음이 BtOH 분획(128.3 mg TA/g, 93.1 mg RT/g), DM 분획(79.5 mg TA/g, 52.9 mg RT/g), EtOH 추출물(78.1 mg TA/g, 55.3 mg RT/g) 순이었다. DPPH 라디칼 소거능은 EA> BtOH${\geq}$ EtOH> DM=DW> Hx 순이었으며, ABTS 라디칼 소거능은 EA> BtOH> EtOH=DM> Hx=DW 분획 순으로 항산화 효과는 EA, BtOH 분획이 가장 우수하였다. 총 페놀화합물의 함량은 DPPH 라디칼 소거능($IC_{50}$)(r=-0.6081, P<0.01), ABTS 라디칼 소거능(r=0.9683, P<0.001)과 유의적인 상관관계를 나타내었으며, DPPH 라디칼 소거능($IC_{50}$)과 ABTS 라디칼 소거능은 서로 유의한 상관관계(r=-0.7172, P<0.001)를 나타내었다. LPS를 처리한 대식세포에 각 추출시료를 세포독성이 없는 농도로 처리한 결과 EtOH 추출물과 Hx, DM, EA 분획이 NO 생성을 유의하게 감소시켰으며(P<0.05), EtOH 추출물과 DM, EA 분획이 PGE2 생성을 유의하게 감소시켰다(P<0.05). 염증성 사이토카인인 IL-6와 TNF-${\alpha}$ 생성은 EtOH 추출물과 Hx, DM, EA, BtOH 분획 모두 유의하게 감소시켰다(P<0.05). 더 나아가 LPS를 처리한 대식세포에서 복숭아꽃 EtOH 추출물을 처리하였을 때 농도의존적으로 iNOS와 COX-2의 합성을 효과적으로 억제시킴으로써 주요한 염증 매개물질인 NO와 PGE2의 생성이 억제되는 기전을 제시하였다. 한편 대식세포에서 분비된 아질산염의 농도는 TNF-${\alpha}$ 농도(r=0.6477, P<0.05) 및 PGE2 농도(r=0.6377, P<0.05)와 유의한 상관관계를 나타내었으며, 아질산염, PGE2, IL-6 농도는 총 페놀화합물 함량이나 항산화 효과 지표들과 유의한 상관성을 보이지 않았다. 다만 TNF-${\alpha}$ 농도만 총 페놀화합물 함량(r=0.6524, P<0.05), 플라보노이드 함량(r=0.6914, P<0.05), DPPH 라디칼 소거능($IC_{50}$)(r=-0.6839, P<0.05), ABTS 라디칼 소거능(r=0.7921, P<0.01)과 각각 유의한 상관관계를 나타내었으며, 염증반응의 매개물질인 PGE2 및 IL-6 농도와는 유의한 상관성이 없었다. 본 실험 결과를 종합하면 복숭아꽃 에탄올 추출물은 항산화 효과와 항염증 효과가 우수하였으며, 그로부터 얻은 분획물 중에서 특히 EA와 BtOH 분획은 항산화 효과가 매우 우수하였고, DM과 EA 분획은 항염증 효과가 우수하였다. 따라서 복숭아꽃 에탄올 추출물을 비롯한 이들 분획물들은 산화적 스트레스 및 염증반응의 상승과 관련되어 있는 만성질환을 예방하는 건강기능성 식품의 개발을 위한 천연소재로 이용 가능할 것으로 기대된다.

• 한국산학기술학회논문지
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• 제20권12호
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• pp.298-305
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• 2019

꾸지뽕나무 뿌리 추출물은 항염, 항암, 항산화와 같은 효과를 갖는 많은 생리활성 물질을 포함하고 있다고 알려져 있다. 그러나 꾸지뽕나무 뿌리 추출물(이하 CTE)의 사람 혈소판 응집 억제 기전에 관하여는 알려진 바 없다. 본 연구에서는 CTE가 혈소판에 미치는 영향을 확인하고자 하였다. CTE는 collagen으로 유도한 혈소판 응집 반응에서 cyclooxygenase-1 활성을 억제하고, 세포 내 칼슘 농도를 낮추는 방식으로 thromboxane A₂ 생성을 억제하였다. 또한, phospholipase Cγ2와 syk의 인산화 반응을 억제하였으며, guanosine monophosphate (cGMP)에 의존적인 방식으로 vasodilator-stimulated phosphoprotein(VASP)의 Ser²³⁹ 위치를 인산화하여 항혈소판 효과를 나타내었다. 또한, 고지방 식이로 혈소판 활성화를 유도한 랫드에서 CTE를 경구 투여 하였을 때, 간독성 없이 콜라겐으로 유도한 혈소판 응집반응을 thromboxane A₂ 생성을 억제함으로써 항혈소판 효과를 보였다. 이는 in vivo와 in vitro에서 같은 결과를 제시하고 있다. 결론적으로, CTE는 항혈소판 작용 및 심혈관계 질환 예방을 위한 천연물 유래의 안전하고, 새로운 물질임을 제시하는 바이다.

• Korean Journal of Radiology
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• 제21권11호
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• pp.1256-1264
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• 2020

Objective: Lung segmentation using volumetric quantitative computed tomography (CT) analysis may help predict outcomes of patients with coronavirus disease (COVID-19). The aim of this study was to investigate the relationship between CT volumetric quantitative analysis and prognosis in patients with COVID-19. Materials and Methods: CT images from patients diagnosed with COVID-19 from February 18 to April 15, 2020 were retrospectively analyzed. CT with a negative finding, failure of quantitative analysis, or poor image quality was excluded. CT volumetric quantitative analysis was performed by automated volumetric methods. Patients were stratified into two risk groups according to CURB-65: mild (score of 0-1) and severe (2-5) pneumonia. Outcomes were evaluated according to the critical event-free survival (CEFS). The critical events were defined as mechanical ventilator care, ICU admission, or death. Multivariable Cox proportional hazards analyses were used to evaluate the relationship between the variables and prognosis. Results: Eighty-two patients (mean age, 63.1 ± 14.5 years; 42 females) were included. In the total cohort, male sex (hazard ratio [HR], 9.264; 95% confidence interval [CI], 2.021-42.457; p = 0.004), C-reactive protein (CRP) (HR, 1.080 per mg/dL; 95% CI, 1.010-1.156; p = 0.025), and COVID-affected lung proportion (CALP) (HR, 1.067 per percentage; 95% CI, 1.033-1.101; p < 0.001) were significantly associated with CEFS. CRP (HR, 1.164 per mg/dL; 95% CI, 1.006-1.347; p = 0.041) was independently associated with CEFS in the mild pneumonia group (n = 54). Normally aerated lung proportion (NALP) (HR, 0.872 per percentage; 95% CI, 0.794-0.957; p = 0.004) and NALP volume (NALPV) (HR, 1.002 per mL; 95% CI, 1.000-1.004; p = 0.019) were associated with a lower risk of critical events in the severe pneumonia group (n = 28). Conclusion: CRP in the mild pneumonia group; NALP and NALPV in the severe pneumonia group; and sex, CRP, and CALP in the total cohort were independently associated with CEFS in patients with COVID-19.

• Journal of Preventive Medicine and Public Health
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• 제43권2호
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• pp.151-158
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• 2010

Objectives: The aim of this study was to evaluate the association between cigarette smoking and total mortality, cancer mortality and other disease mortalities in Korean adults. Methods: A total of 14 161 subjects of the Korean Multi-center Cancer Cohort who were over 40 years of age and who were cancer-free at baseline enrollment reported their lifestyle factors, including the smoking status. The median follow-up time was 6.6 years. During the follow-up period from 1993 to 2005, we identified 1159 cases of mortality, including 260 cancer mortality cases with a total of 91 987 person-years, by the national death certificate. Cox proportional hazard regression model was used to estimate the hazard ratio (HR) of cigarette smoking for total mortality, cancer mortality and disease-specific mortality, as adjusted for age, gender, the geographic area and year of enrollment, the alcohol consumption status, the education level and the body mass index (BMI). Results: Cigarette smoking was significantly associated with an increased risk of total mortality, all-cancer mortality and lung cancer mortality (p-trend, < 0.01, <0.01, <0.01, respectively). Compared to non-smoking, current smokers were at a higher risk for mortality [HR (95% CI)=1.3 (1.1 - 1.5) for total mortality; HR (95% CI)=1.6 (1.1 -2.2) for all-cancer mortality; HR (95% CI)=3.9 (1.9-7.7) for lung cancer mortality]. Conclusions: This study's results suggest that cigarette smoking might be associated with total mortality, all-cancer mortality and especially lung cancer mortality among Korean adults.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.299-304
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• 2014

Cholangiocarcinoma (CCA), a malignancy of biliary duct with a very poor prognosis, is the leading cause of cancer death in countries of the Mekong subregion. Liver fluke infection is the main etiological factor, but genetic variation has been recognized as also important in conferring susceptibility to CCA risk. Nuclear factor (erythroid derived 2)-like 2 (NRF2) is a key transcription factor in detoxification and antioxidant defense. Emerging evidence has demonstrated that genetic polymorphisms in the NRF2 gene may be associated with cancer development. The objectives of this study were to investigate the association of NRF2 genetic polymorphism with CCA risk and to evaluate the influence of the NRF2 genotype on survival time of affected patients. Single nucleotide polymorphisms (SNPs) of the NRF2 gene, including rs6726395: A/G, rs2886161: C/T, rs1806649: C/T, and rs10183914: C/T, were analyzed using TaqMan$^{(R)}$ SNP genotyping assays. Among 158 healthy northeastern Thai subjects, the allele frequencies were 41, 62, 94, and 92%, respectively. The correlation of NRF2 SNPs and CCA risk was analyzed in the 158 healthy subjects and 198 CCA patients, using unconditional logistic regression. The results showed that whereas the NRF2 SNPs were not associated with CCA risk (p>0.05), Kaplan-Meier analysis of 88 intrahepatic CCA patients showed median survival time with rs6726395 genotypes of GG and AA/AG to be $344{\pm}138$ (95%CI: 73-615) days and $172{\pm}37$ (95%CI: 100-244) days, respectively, (p<0.006). On multivariate Cox proportional hazard analysis, the GG genotype of rs6726395 was found to be associated with longer survival with a hazard ratio of 0.54 (95%CI: 0.31-0.94). In addition, non-papillary adenocarcinoma was associated with poor survival with a hazard ratio of 2.09 (95%CI: 1.16-3.75). The results suggest that the NRF2 rs6726395 polymorphism can be a potential prognostic biomarker for CCA patients.