• 한국식품영양학회지
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• 제35권6호
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• pp.464-472
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• 2022

The present study was designed to investigate the antiproliferative activity and molecular mechanisms of Bibimbap in HT-29 human colorectal adenocarcinoma cells. Bibimbap extract inhibited the proliferation of HT-29 cells by 50% at a concentration of 10.1±0.17 mg/mL for 48 h. The population of live cells decreased slightly, and the morphology changed with a reduction in cell volume (pyknosis) with Bibimbap. Treatment with 5 mg/mL of Bibimbap resulted in slight cell shrinkage. Furthermore, as the Bibimbap dose increased to 10 mg/mL, these characteristics were more evident, and HT-29 cells exhibited partial detachment by staining with the DNA-binding dye Hoechst 33342. Flow cytometric analysis by Annexin V and PI double staining showed that Bibimbap increased the levels of apoptosis. Analysis of the mechanism of these events showed that Bibimbap-treated cells exhibited a mitochondria-dependent apoptotic pathway through the modulation of caspase-3, caspase-8, caspase-9, and poly-ADP ribose polymerase, as well as Bax and Bcl-2 expression in dose- and time-dependent manners. Consequently, Bibimbap exerts a significant antiproliferative effect on HT-29 human colorectal adenocarcinoma cells.

• 농업과학연구
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• 제47권1호
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• pp.83-93
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• 2020

Lactoferrin (LF) is an iron-binding glycoprotein that is present in colostrum, milk, and other body secretions. The objective of this study was to investigate the effects of lactoferrin hydrolysates (LHs) on the production of immunomodulatory factors, including inflammatory related cytokines. The nuclear factor (NF)-κB reporter assay using human embryonic kidney 293 cells (HEK-293) revealed that NF-κB activity was significantly decreased by 1, 50, and 100 ㎍/mL of LH and the fractions above and below the 10 kDa LH. The mRNA expression of interferon (IFN)-γ in rat basophilic leukemia mast cells (RBL-2H3) treated with the fraction above the 10 kDa LH decreased in a dose-dependent manner, but the cells treated with LH and the fraction below the 10 kDa LH showed an increased expression of IFN-γ in a dose-dependent manner. The level of cyclooxygenase (COX)-2 expression decreased dose-dependently in RBL-2H3 cells treated with LH and the fraction above the 10 kDa LH, but the cells treated with the fraction below the 10 kDa LH showed an increased COX-2 expression in a dose-dependent manner. The mRNA expression of interleukin (IL)-4) was dose-dependently decreased by the fraction below the 10 kDa LH in human mast cells (HMC-1). The mRNA expressions of tumor necrosis factor (TNF)-α and IL-6 were significantly dose-dependently decreased by the fractions above and below the 10 kDa LH, but was dose-dependently increased by LH. The production of IL-4 was a little increased by the fraction above the 10 kDa LH compared to the positive control, but was decreased with LH and the fraction below the 10 kDa LH in HMC-1 cells. It was concluded that LF hydrolysates had an immunomodulating effect on anti-, pro-inflammatory and anti-allergic reactions.

• 한국의학물리학회지:의학물리
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• 제22권4호
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• pp.163-171
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• 2011

본 연구에서는 피사체에 의한 산란, 초점에 의한 흐림, 기하학적 확대도 그리고 검출기의 특성이 반영된 유효검출양자효율(effective detective quantum efficiency, eDQE)과 유효선량을 평가하여 소아 흉부 X선 촬영 시 선량의 최적화를 위한 조사조건의 영향을 평가하였다. 100, 110, 120, 150, 180 cm의 FDD (focus-to-detector distance)일 때 관전압을 40 kVp에서 90 kVp까지 10 kVp씩 증가시켜가며 동일한 유효선량일 때 eDQE를 평가하였다. 그 결과 eDQE는 다른 관전압과 비교 시60 kVp에서 가장 높은 값을 보였다. 특히, 동일한 유효선량일 때 그리드가 없을 경우 상대적으로 매우 높은 eDQE를 나타냈다. 이는 그리드에 의한 산란선의 감소가 그리드에서 흡수된 유효 광자의 손실을 보상하지 못하기 때문이다. 그리드 가 없을 경우 FDD가 증가할수록 향상된 유효변조전달함수(effective modulation transfer function, eMTF)로 인하여 eDQE는 증가하였다. 국내 대형병원들의 대부분은 15개월 소아의 흉부 X선 촬영 시 그리드와 함께 100 cm의 짧은 FDD를 사용하고 있다. 그 결과 대부분의 경우는 국내 환자선량권고량(diagnostic reference level, DRL) $100{\mu}Gy$을 초과하였다. 이는 5세 소아 흉부 X선 촬영 시 150 cm에서 180 cm 사이의 긴 FDD를 사용하지만, 15개월을 모사하고 있는 표준 소아팬텀의 흉부 X선 촬영의 경우 100 cm의 짧은 FDD를 사용했기 때문이다. 따라서, 나이에 따른 소아의 흉부 X선 촬영을 시행하기 위한 적절한 조사조건이 확립되어야 한다. 본 연구 결과는 나이에 따른 소아 선량의 권고량을 설립하는데 기초자료로 활용될 수 있을 것이다.

• 한국의학물리학회지:의학물리
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• 제26권1호
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• pp.28-35
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• 2015

본 논문에서는 반복적 구성 기법과 관전류 노출자동조절 기법이 영상의 화질과 방사선량에 미치는 영향을 관상동맥 전산화단층촬영 혈관조영 영상(coronary computed tomography angiography, CCTA)을 대상으로 팬텀 실험에 기반하여 평가하고자 한다. 이를 위하여 미국 의학물리학회(American Association of Physics in Medicine) 표준의 성능 평가 팬텀을 320 다중검출열 CT로써 촬영하였다. 80 kVp, 100 kVp, 120 kVp의 관전압에 있어서, 관전류 노출자동조절 기법은 저선량 목표 표준편차(SD=44)와 고선량(목표 표준편차=33)의 두 가지 설정으로써 촬영하였다. 재구성 변수로서는 필터보정 역투영(FBP)와 반복적 재구성 방법을 설정하여, 전부 12개의 재구성 영상을 획득하였다(12=3 (80, 100, 120 kVp)${\times}2$ (저선량(목표SD=44), 고선량(목표SD=33))${\times}2$ (필터보정역투영, 반복적 재구성). 영상의 화질은 잡음의 세기(표준편차), 변조전달함수, 대조대잡음비(CNR)에 의하여 평가하였으며, 관전압과 관전류 노출자동조절 기법에서의 목표 선량과 대소 및 재구성 기법의 선택이 화질과 방사선량에 미치는 영향을 관찰하였다. 반복적 재구성 기법은 필터보정역투영 기법보다 영상 잡음을 대폭 감소시켰으며 이는 저선량의 경우 더욱 뚜렷하였다. 즉, 잡음의 세기는 관전류 노출자동조절의 설정이 고선량 (목표SD=33)과 저선량(목표SD=44)인 경우, 각각 평균 38%와 평균 46% 감소하였다. 반복적 재구성 기법에 의하여, 변조전달 함수에 의한 공간적 해상도의 평가에 있어서 미약한 감소를 보였으나, 이로써 잡음 저감과 대조대잡음비(CNR)에 있어서의 현저한 개선을 상쇄할 정도의 영향에는 미치지 못 하였다. 결과적으로, 관상동맥 전산화단층촬영 혈관조영 영상의 획득에서 있어서, 반복적 재구성 기법과 관전류 노출자동조정 기법을 동시에 사용하는 것은 영상의 화질을 개선하면서 공간적 해상도의 저하 등 그 부작용은 최소화함으로써, 합리적으로 획득 가능한 한 최소한의 선량 (ALARA)의 원칙에 충실한 실제 임상적 효과를 의미한다고 기대할 수 있다.

• Radiation Oncology Journal
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• 제23권1호
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• pp.51-60
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• 2005

목적 : 분자 표적의 선택적 억제가 방사선 세포 살상 효과를 증진시키는 것으로 알려져 있으므로 선택적 COX-2 억제제와 EGF 수용체 차단제를 HeLa 세포주에 처리한 후 방사선 효과의 상승작용을 알아보고자 하였다. 대상 및 방법 : 자궁경부암 세포주인 HeLa세포에서 EGF 수용체 차단제 AG 1478, 선택적 COX-2 억제제 NS 398과 방사선을 복합 투여하여 세포성장 억제 분석(cell graph inhibition assay)과 세포사멸 분석(apoptosis assay)을 시행하였고, 방사선 감수성 변화를 살펴보기 위해 세포생존 분석(clonogenic survival assay)을 시행하였다. 방사선 감수성 인자로는 2 Gy에서의 세포생존분획($SF_2$)과 linear-quadratic model을 이용한 dose enhancement ratio (DER)를 사용하였다. 방사선 감수성에 대한 작용기전 분석을 위해 flow cytometry로 세포주기 분석(cell cycle analysls)을 시행하였고, western blot 분석을 통하여 bcl-2와 bax 단백질의 발현 변화를 살펴보았다. 결과 : HeLa세포에 NS 398과 AG 1478을 방사선과 함께 복합 투여한 실험 군에서 세포사멸 정도가 가장 높게 나타났다($8.49\%$ vs. $22.70\%$). 세포주기 분석 결과, 방사선과 복합 약물 처리군에서 $G_0/G_l$ 세포주기 정체와 5 세포 분획 소실이 나타났으며 이러한 변화는 72시간 이후까지 지속되었다 세포생존 분석 결과로는 방사선과 AG 1478군에서 $SF_{2}0.68{\pm}0.07$, DER 1.12를 보인 반면, 방사선과 복합약물처리군에서는 $SF_{2}0.12{\pm}0.01,\;DER\;3.00$으로 나타났다. Western blot분석에서는 방사선과 복합약물처리군에서 bcl-2와 bax 단백질 발현이 모두 감소하는 양상을 보였다. 결론 : 신호전달 체계를 억제하는 분자 표적 약제인 선택적 COX-2 억제제와 EGF 수용체 차단제를 방사선과 복합투여함으로써 HeLa세포의 방사선 감수성이 증가됨을 확인하였다.

• 동의생리병리학회지
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• 제17권6호
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• pp.1514-1518
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• 2003

Angelica sinensis radix, Danggui, is a traditional oriental medication, which has been used to modulate immune response. We report here that aqueous extract of Angelica sinensis radix (ASR) can induces NO production, and inhibit LPS-induced NO production in dose-dependent manner in RAW 264.7 macrophage cells. ASR also induces iNOS mRNA and iNOS protein expression, and exhibit inhibitory effect on iNOS mRNA and protein expression in a dose-dependent manner in LPS-stimulated RAW 264.7 macrophage cells. Cytokines involved in the regulation of inflammatory reaction and immune response may play a role in the pathogenesis. ASR induces. pro-inflammatory cytokine gene expression (IL-1α, IL-1β and IL-6 gene) in a dose-dependent manner, and inhibits the expressions of these cytokines in LPS-stimulated RAW 264.7 macrophage cells. These data indicate that (1) ASR may be a potential therapeutic modulator of NO synthesis in various pathological conditions, and (2) the immunomodulatory effects of ASR may be, in part, associated with the inducing or suppression of pro-inflammatory cytokine gene expressions.

• Toxicological Research
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• 제26권3호
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• pp.223-232
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• 2010

Artesunate, a semi-synthetic derivative of artemisinin, is used primarily as a treatment for malaria. Its effects on the central nervous system, general behavior, and cardiovascular, respiratory, and other organ systems were studied using mice, rats, guinea pigs, and dogs. Artesunate was administered orally to mice at doses of 125, 250, and 500 mg/kg and to rats and guinea pigs at 100, 200, and 400 mg/kg. In dogs, test drugs were administered orally in gelatin capsules at doses of 50, 100, and 150 mg/kg. Artesunate induced insignificant changes in general pharmacological studies, including general behavior, motor coordination, body temperature, analgesia, convulsion modulation, blood pressure, heart rate (HR), and electrocardiogram (ECG) in dogs in vivo; respiration in guinea pigs; and gut motility or direct effects on isolated guinea pig ileum, contractile responses, and renal function. On the other hand, artesunate decreased the HR and coronary flow rate (CFR) in the rat in vitro; however, the extent of the changes was small and they were not confirmed in in vivo studies in the dog. Artesunate increased hexobarbital-induced sleeping time in a dose-related manner. Artesunate induced dose-related decreases in the volume of gastric secretions and the total acidity of gastric contents, and induced increases in pH at a dose of 400 mg/kg. However, all of these changes were observed at doses much greater than clinical therapeutic doses (2.4 mg/kg in humans, when used as an anti-malarial). Thus, it can be concluded that artesunate is safe at clinical therapeutic doses.

• 한국축산식품학회지
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• 제34권6호
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• pp.829-835
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• 2014

Inflammatory bowel disease (IBD) is caused by dysregulation of colon mucosal immunity and mucosal epithelial barrier function. Recent studies have reported that lipoteichoic acid (LTA) from Lactobacillus plantarum K8 reduces excessive production of pro-inflammatory cytokine. In this study, we investigated the preventive effects of lysate of Lb. plantarum K8 in dextran sulfate sodium (DSS)-induced colitis. Male Sprague-Dawley rats were orally pretreated with lysate of Lb. plantarum K8 (low dose or high dose) or live Lb. plantarum K8 prior to the induction of colitis using 4% DSS. Disease progression was monitored by assessment of disease activity index (DAI). Histological changes of colonic tissues were evaluated by hematoxylin and eosin (HE) staining. Tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin-6 (IL-6) levels were measured using enzyme-linked immunosorbent assay (ELISA). The colon mRNA expressions of TNF-${\alpha}$, IL-6, and toll like receptor-2 (TLR-2) were examined by quantitative real-time-transcription polymerase chain reaction (qPCR). Lysate of Lb. plantarum K8 suppressed colon shortening, edema, mucosal damage, and the loss of DSS-induced crypts. The groups that received lysate of Lb. plantarum K8 exhibited significantly decreased levels of the pro-inflammatory cytokines TNF-${\alpha}$ and IL-6 in the colon. Interestingly, colonic expression of toll like receptor-2 mRNA in the high-dose lysate of Lb. plantarum K8 group increased significantly. Our study demonstrates the protective effects of oral lysate of Lb. plantarum K8 administration on DSS-induced colitis via the modulation of pro-inflammatory mediators of the mucosal immune system.

• Genomics & Informatics
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• 제20권3호
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• pp.32.1-32.15
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• 2022

Malaria is a life-threatening disease, and Africa is still one of the most affected endemic regions despite years of policy to limit infection and transmission rates. Further, studies into the variable efficacy of the vaccine are needed to provide a better understanding of protective immunity. Thus, the current study is designed to delineate the effect of each dose of vaccine on the transcriptional profiles of subjects to determine its efficacy and understand the molecular mechanisms underlying the protection this vaccine provides. Here, we used gene expression profiles of pre and post-vaccination patients after various doses of RTS,S based on samples collected from the Gene Expression Omnibus datasets. Subsequently, differential gene expression analysis using edgeR revealed the significantly (false discovery rate < 0.005) 158 downregulated and 61 upregulated genes between control vs. controlled human malaria infection samples. Further, enrichment analysis of significant genes delineated the involvement of CCL8, CXCL10, CXCL11, XCR1, CSF3, IFNB1, IFNE, IL12B, IL22, IL6, IL27, etc., genes which found to be upregulated after earlier doses but downregulated after the 3rd dose in cytokine-chemokine pathways. Notably, we identified 13 cytokine genes whose expression significantly varied during three doses. Eventually, these findings give insight into the dual role of cytokine responses in malaria pathogenesis. The variations in their expression patterns after various doses of vaccination are linked to the protection as it decreases the severe inflammatory effects in malaria patients. This study will be helpful in designing a better vaccine against malaria and understanding the functions of cytokine response as well.

• 한국식생활문화학회지
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• 제36권2호
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• pp.235-245
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• 2021

Lindera glauca Blume has been used in Korean traditional medicine to treat the symptoms of paralysis, abdominal pain, speech disorders, extravasations, contusions, and pain caused by rheumatoid arthritis. We investigated the effect of L. glauca Blume extracts on the proliferation of colorectal cancer cells in vitro using HCT116 human colorectal cancer cell lines. We also investigated its mechanism of action. For this purpose, we used the MTT assay, western blotting, DNA fragmentation analysis, and flow cytometry. HCT116 cells were cultured in several concentrations of ethanol extracts of L. glauca Blume root (0, 50, 100 ㎍/mL). In this study, colon cancer cell growth was inhibited by L. glauca Blume root extract in a dose-dependent manner. It was associated with induction of apoptosis as assessed by nuclear fragmentation and cell cycle analysis. Apoptosis was assessed using western blotting for TNF-α, IL-6, NF-κB, Caspase-3, PARP, Bax, Bcl-2, and SIRT1. The extract also dose-dependently upregulated the expression Bax, the pro-apoptotic gene and downregulated the expression of the anti-apoptotic gene Bcl-2. Furthermore, the extract enhanced Caspase-3 activity in a dose-dependent manner. Our findings provide evidence that L. glauca Blume extract may mediate its anti-proliferative effect via the modulation of apoptosis.