Anti-Inflammatory Effect for Atherosclerosis Progression by Sodium-Glucose Cotransporter 2 (SGLT-2) Inhibitor in a Normoglycemic Rabbit Model

이슬기,Seung-Jun Lee,Jung-Jae Lee,Jung-SunKim,Oh-Hyun Lee,김충기,Darae Kim,Yong-Ho Lee,JaeWonOh,Se Il Park,전옥희,Sung-Jin Hong,Chul-Min Ahn,Byeong-Keuk Kim,Young-Guk Ko,Donghoon Choi,Myeong-Ki Hong,Yangsoo Ja 대한심장학회 2020 Korean Circulation Journal Vol.50 No.5

Background and Objectives: We sought to investigate an anti-atherosclerotic and anti-inflammatory effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in normoglycemic atherosclerotic rabbit model. Methods: Male New Zealand white rabbits (n=26) were fed with a 1% high-cholesterol diet for 7 weeks followed by normal diet for 2 weeks. After balloon catheter injury, the rabbits were administered with the Dapagliflozin (1mg/kg/day) or control-medium for 8 weeks (n=13 for each group). All lesions were assessed with angiography, optical coherence tomography (OCT), and histological assessment. Results: Atheroma burden (38.51±3.16% vs. 21.91±1.22%, p<0.01) and lipid accumulation (18.90±3.63% vs. 10.20±2.03%, p=0.047) was significantly decreased by SGLT-2 inhibitor treatment. The SGLT-2 inhibitor group showed lower macrophage infiltration (20.23±1.89% vs. 12.72±1.95%, p=0.01) as well as tumor necrosis factor (TNF)-α expression (31.17±4.40% vs. 19.47±2.10%, p=0.025). Relative area of inducible nitric oxide synthase+ macrophages was tended to be lower in the SGLT-2 inhibitor-treated group (1.00±0.16% vs. 0.71±0.10%, p=0.13), while relative proportion of Arg1+ macrophage was markedly increased (1.00±0.27% vs. 2.43±0.64%, p=0.04). As a result, progression of atherosclerosis was markedly attenuated in SGLT-2 inhibitor treated group (OCT area stenosis, 32.13±1.20% vs. 22.77±0.88%, p<0.01). Mechanistically, SGLT-2 treatment mitigated the inflammatory responses in macrophage. Especially, Toll-like receptor 4/nuclear factor-kappa B signaling pathway, and their downstream effectors such as interleukin-6 and TNF-α were markedly suppressed by SGLT-2 inhibitor treatment. Conclusions: These results together suggest that SGLT-2 inhibitor exerts an anti-atherosclerotic effect through favorable modulation of inflammatory response as well as macrophage characteristics in non-diabetic situation.

새만금유역 밭경지 초생대 유사저감효과 모의

이슬기,장정렬,최경숙,Lee, Seul Gi,Jang, Jeong Ryeol,Choi, Kyung Sook 한국수자원학회 2018 한국수자원학회논문집 Vol.51 No.6

본 연구에서는 VFSMOD-W 모형을 활용하여 새만금 유역의 초생대 기법 적용에 따른 유사저감효과를 예측하고자 하였다. 먼저 모형의 신뢰도 확보를 위해 새만금 유역 내 초생대 실측치를 활용하여 매개변수를 보정하였으며, 새만금 유역 내 밭경지 특성을 파악하여 이를 토대로 모의 시나리오를 개발하였다. 다양한 밭경지 특성을 반영하기 위해 개발된 모의시나리오는 밭경지 규모 1 ha, 5 ha, 10 ha로 밭의 폭과 길이 비는 1 : 1를 적용하였으며, 밭의 경사는 7%, 15%를 고려하였다. 또한 강우조건은 50 mm, 100 mm, 150 mm, 200 mm 일강우량을 적용하였다. 그 결과, 초생대의 유출저감효과는 밭경사 7%와 15%에 대해 2.9~13.5%, 2.9~12.1%로 각각 나타났으며, 유사저감효과는 33.8~97.0%, 27.1~85.9%로 각각 나타나 유출저감효과에 비해 상대적으로 높은 저감효과를 나타내었다. 유출 및 유사 발생에 영향을 미치는 밭규모, 경사 및 강우량 인자에 따라 초생대 효과는 큰 차이를 나타내었다. 본 모의 결과를 바탕으로 새만금 유역내 밭경지 규모 10 ha 미만, 경사 15% 이내의 조건에서 밭면적 10% 규모로 초생대를 조성할 경우 유사저감 효과를 기대할 수 있을 것으로 사료된다. The study was intended to simulate the sediment reduction effects of the Vegetative Filter Strip (VFS) in uplands of Saemangeum watershed through VFSMOD-W model application. The model was calibrated by using the field data and the simulation scenarios were designed based on the investigation of uplands characteristics in Saemangeum watershed. The simulation scenarios were considered various size and slope of uplands including 1 ha, 5 ha, 10 ha of field size with width-length ratio of 1 : 1 having 7% and 15% of slopes under the daily rainfall of 50 mm, 100 mm, 150 mm, and 200 mm in order to mimic the different fields conditions. The effluent reduction ranged from 2.9~13.5% and 2.9~12.1% for runoff, and 33.8~97.0% and 27.1~85.9% for sediment under the field's slope of 7% and 15%, respectively. The VFS reduction effects showed different degree of influence from field size, slope, rainfall amounts. Based on the simulated results, the sediment contributing non-point source pollution expected to be reduced in the condition of VFS constructed 10% of fields in outlet of less than 10 ha of uplands having less than 15% of the slope.

증미이진탕(增味二陳湯) 투여가 역류성 식도염 유발 생쥐에 미치는 영향

이슬기,임성우,Lee, Seul-ki,Lim, Seong-woo 대한한방내과학회 2016 大韓韓方內科學會誌 Vol.37 No.6

Objectives: This study investigated the administration of Jeungmiyijin-tang (JYT) to rats with reflux esophagitis (RE) induced by pylorus and forestomach ligation operations. Methods: Twenty laboratory rats were divided into three groups with 5~7 rats in each group. The control group consisted of rats with no inflammation (CON). The RE group had rats with gastroesophageal reflux elicited by pylorus and forestomach ligation operations. The JYT group had rats that were orally administered Jeungmiyijin-tang (1.5 ml/day/300 g) once a day for 14 days before reflux esophagitis was induced by the pylorus and forestomach ligation operations. Six hours after the operations, the rats were sacrificed, morphological changes were observed, and histological examinations were done in the stomach and esophagus lesion areas. If apoptosis was observed, the apoptotic cells in the esophagus lesion areas were counted. Results: The morphological and histochemical changes consisted of various injuries from hemorrhagic erosion in the RE group, while there were significantly fewer in the JYT group. The RE group marked increases of gastric mucosa erosion and infiltration of inflammatory cells in the submucosa, as well as cell division in the epithelial layer, the proliferation and degranulation of mast cells, and increases in the IL-$1{\beta}$, TNF-${\alpha}$, and MMP-9 expressions in the esophagus of the rats. The JYT group was inhibited above expression compared with the RE group. Apoptosis was statistically significantly decreased in the JYT group compared with the RE group. Conclusions: According to the above results, it appears that Jeungmiyijin-tang inhibits the expression of pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$, and MMP-9) and apoptosis in the esophagus mucosa, thereby preventing esophageal mucosal damage from esophageal reflux.

Chitosan-HNT 복합막을 이용한 기체 투과특성에 관한 연구

이슬기,홍세령,Lee, Seul Ki,Hong, Se Ryeong 한국막학회 2014 멤브레인 Vol.24 No.5

Chitosan에 HNT (halloysite nanotube)의 함량을 0, 3, 5, 10 wt%로 가하여 chitosan-HNT 복합막을 제조하였다. 복합막의 구조는 FT-IR, XRD, TGA, SEM으로 알아보았다. 기체투과 실험은 $30^{\circ}C$, $4kg/cm^2$ 조건에서 수행하였고, chitosan-HNT 복합막의 HNT 함량 변화에 따른 $CO_2$와 $CH_4$의 기체투과도와 선택도를 조사하였다. Chitosan-HNT 복합막의 기체 투과도는 HNT 함량이 3 wt%에서 가장 큰 값을 보였고, 그 이상의 함량에서는 감소하였다. 선택도($CO_2/N_2$)는 0~10 wt% 범위에서 HNT 내의 OH기와 $CO_2$ 간의 친화력으로 인하여 증가하였고, 약 1.3~3.8의 값을 보였다. Chitosan-HNT (halloysite nanotube) composite membranes were prepared by the addition of HNT 0, 3, 5, and 10 wt%. The structure of composite membranes were studied by FT-IR, XRD, TGA, and SEM. Gas permeation experiment were performed under condition of $30^{\circ}C$ and $4kgf/cm^2$. Gas permeability and selectivity were investigated by increasing the amount of HNT contents in the chitosan. Chitosan-HNT composite membrane for $CO_2$ and $CH_4$ showed the maximum value at 3 wt% of HNT content and decreased thereafter. The selectivity of ($CO_2/CH_4$) was increased due to its affinity with the OH groups on the HNT, was shown in the range of 1.3 to 3.8 at 0~10 wt%.

Sentinel-2 위성영상을 이용한 DMZ 산불 피해 면적 관측 기법 연구

이슬기,송종성,이창욱,고보균,Lee, Seulki,Song, Jong-Sung,Lee, Chang-Wook,Ko, Bokyun 대한원격탐사학회 2022 大韓遠隔探査學會誌 Vol.38 No.5

본 연구는 직접적인 접근이 어려운 demilitarized zone (DMZ)의 산불 피해 지역을 파악하기 위하여, 고해상도 위성영상 및 머신러닝 기반의 감독 분류 기법을 이용하였다. 고해상도 위성 영상은 Sentinel-2 A/B를 이용하였으며, SVM 감독분류 기법을 기반으로 토지피복도를 산출하였다. DMZ 산불 피해 지역을 분류하기 위한 최적의 조합을 찾기 위하여 SVM 내에 다양한 커널과 밴드 조합에 따른 감독 분류를 진행하고 오차 행렬을 통해 정확도를 평가하였다. 또한, 2020년, 2021년은 위성영상 자료 기반의 산불 탐지 결과와 산불 연보의 피해 지역 면적 간의 비교를 통한 검증을 수행하였다. 이후, 현재 피해 면적 자료가 없는 2022년의 산불 피해 지역을 탐지함으로써 신뢰할 만한 수준의 결과를 신속적으로 파악하고자 하였다. This study used high-resolution satellite images and supervised classification technique based on machine learning method in order to detect the areas affected by wildfires in the demilitarized zone (DMZ) where direct access is difficult. Sentinel-2 A/B was used for high-resolution satellite images. Land cover map was calculated based on the SVM supervised classification technique. In order to find the optimal combination to classify the DMZ wildfire damage area, supervised classification according to various kernel and band combinations in the SVM was performed and the accuracy was evaluated through the error matrix. Verification was performed by comparing the results of the wildfire detection based on satellite image and data by the wildfire statistical annual report in 2020 and 2021. Also, wildfire damage areas was detected for which there is no current data in 2022. This is to quickly determine reliable results.

밭 비점오염저감을 위한 잔디초생대 적용 비용 및 활용성 평가

이슬기,장정렬,최경숙,Lee, Seul-Gi,Jang, Jeong-Ryeol,Choi, Kyung-Sook 한국농공학회 2015 한국농공학회논문집 Vol.57 No.2

This study was aimed to estimate the total application cost and utilization of Turf grass VFS application through the field experiment. The experimental plots were constructed in an upland field of Iksan city within the Saemangeum watershed. Turf grass was transplanted at the down-slope edge of the pollution source area in each of the treated plots. Three rainfall events were monitored during the experiment period, and the rainfall-runoff relationships and NPS pollution reduction effects of the VFS systems were assessed. As results, the reduction ratio of runoff volume ranged 14.1~64.0 %, while the NPS pollution reduction ratio ranged 9.8~73.9 % for SS, 24.0~84.2 % for T-N, 31.6~80.9 % for T-P respectively. The total cost of VFS application was estimated by considering purchase cost of Turf grass sods and construction and maintenance costs of VFS system as well as the loss caused by giving up crop cultivation for the area needed to construct the VFS. The total cost of the VFS was estimated to be approximately \3,379,000/ha/year for the first year of application, and this cost could be decreased to \1,899,000/ha/year from the second year as the construction cost of VFS could no longer need to be counted afterwards. Apart from the NPS pollution reduction effects, the possible utilization of VFS was examined by detaching Turf grass within 40 % of VFS area for sale during spring time when the VFS systems fully covered. The benefit of selling the detached Turf grass sods was estimated as \1,260,000/ha/year, and also found that the VFS area successfully recovered by the time of the summer period. This benefit could attract farmers to adopt the VFS technique to manage agricultural NPS pollution.

익산 밭경지 특성을 고려한 초생대 유출 및 유사 저감효과 모의

이슬기,장정렬,최경숙,Lee, Seul Gi,Jang, Jeong Ryeol,Choi, Kyung Sook 한국농공학회 2014 한국농공학회논문집 Vol.56 No.5

The goal of this study was to evaluate sediment reduction effects of VFS (vegetative filter strip) applied for Iksan area in Saemangeum watershed. This study simulated runoff and sediment load from different types of uplands using VFSMOD-W. The general upland characteristics of the study area was investigated to build reasonable scenarios of the simulation. The simulation scenarios were designed by various areas, shapes, and slopes of uplands. Grass mixture was selected as VFS vegetation and the size of VFS was fixed as 10 % of uplands area. Additionally 50mm, 100mm, 150mm of daily rainfall were applied for the runoff and sediment simulation. As results, the calculated runoff and sediment loads were obtained $20.7{\sim}1,030.6m^3$ and 568.4~675,731.4 kg for the range of 0.1~1.0 ha of uplands with 7 % and 15 % slopes. The reduction effects on runoff and sediment were obtained 5~10 % and 21.0~47.7 % respectively from VFS applications. The VFSMOD-W simulations showed that runoff tended to increase as upland area and amount of rainfall increased while sediment increased when slope, length and area of uplands and amount of rainfall increased. These results indicated that rainfall amount and upland size are the critical factors for the generation of runoff and sediment load. In order to support this conclusion, further studies such as, long term monitoring, field experiments, and to calibrate and evaluate the model are necessary.

Anti-tumor effect of Inonotus obliquus in xenograft animals with EBV+human gastric carcinoma

이슬기,조효선,Lee, Seulki,Cho, Hyosun The Microbiological Society of Korea 2016 미생물학회지 Vol.52 No.4

차가버섯(Inonotus obliquus)은 다양한 생리활성을 가진 약용버섯으로 항암, 항산화, 항염효능 등을 가진 것으로 보고되었다. EBV 양성 위암은 EBV관련 암 중 가장 빈번하게 나타나는 형태로 EBV 잠복감염이 그 원인이다. 본 연구에서는 차가버섯 주정추출물의 경구투여를 통해 EBV 양성 인간위암(SNU719) 세포주를 면역결핍 쥐에 주입 후 생기는 고형암 생성억제에 대한 효능을 연구하였다. 또한, 실험종료 후, 각각의 종양조직을 절제하여 항종양 억제기전을 탐구하였다. In vivo 종양생성억제 실험에서 차가버섯은 유의적으로 고형암 생성억제 효능을 보였다. 차가버섯이 투여된 동물유래 종양조직에서 세포자멸사와 관련된 p53, p21 및 Bax의 발현이 크게 증가하였으며, 이는 cleaved caspase-9와 cleaved Parp 발현의 상승과 동반하여 항종양 효능이 세포자멸사를 통해 나타남을 제시하였다. 또한, 이러한 항종양 효능은 세포주 내 잠복되어 있는 EBV 바이러스 유전자인 BZLF-1 및 LMP-2의 발현에도 영향을 미치는 것으로 밝혀졌다. Inonotus obliquus is a medicinal mushroom with a variety of biological activities. It has reported to have strong anti-cancer, antioxidant and anti-inflammatory properties. EBV+ gastric carcinoma is one of the most common EBV-associated cancers that were caused by latent EBV infection. In this study, we investigated the anti-cancer effects of ethanol extract of I. obliquus using in vivo xenograft animal models implanted with EBV+ human gastric carcinoma (SNU719). We also explored the molecular mechanisms responsible for its anti-cancer activity. The result indicated that the extract of I. obliquus had an anti-cancer effect in in vivo xenograft mice with EBV+ gastric carcinoma (SNU719). Extract of I. obliquus also showed a great effect on inducing the expression of p53, p21 and Bax in tumor tissue derived from EBV+ human gastric carcinoma, and these were correlated with increased expressions of the cleaved forms of caspase-9 and Parp. Also, I. obliquus attenuated the expression of viral proteins, BZLF-1 and LMP-2 in tumor tissue from EBV+ human gastric carcinoma.

Genome-Wide Screen of Human Bromodomain-Containing Proteins Identifies Cecr2 as a Novel DNA Damage Response Protein

이슬기,권종범,박은정,이한새,Ye Seul Lee 한국분자세포생물학회 2012 Molecules and cells Vol.34 No.1

The formation of -H2AX foci after DNA double strand breaks (DSBs) is crucial for the cellular response to this lethal DNA damage. We previously have shown that BRG1, a chromatin remodeling enzyme, facilitates DSB repair by stimulating -H2AX formation, and this function of BRG1 requires the binding of BRGI to acetylated histone H3 on -H2AX-containing nucleosomes using its bromodomain (BRD), a protein module that specifically recognizes acetyl-Lys moieties. We also have shown that the BRD of BRG1, when ectopically expressed in cells, functions as a dominant negative inhibitor of the BRG1 activity to stimulate -H2AX and DSB repair. Here, we found that BRDs from a select group of proteins have no such activity, suggesting that the -H2AX inhibition activity of BRG1 BRD is specific. This finding led us to search for more BRDs that exhibit -H2AX inhibition activity in the hope of finding additional BRD-containing proteins involved in DNA damage responses. We screened a total of 52 individual BRDs present in 38 human BRD-containing proteins, comprising 93% of all human BRDs. We identified the BRD of cat eye syndrome chromosome region candidate 2 (Cecr2), which recently was shown to form a novel chromatin remodeling complex with unknown cellular functions, as having a strong -H2AX inhibition activity. This activity of Cecr2 BRD is specific because it depends on the chromatin binding affinity of Cecr2 BRD. Small interfering RNA knockdown experiments showed that Cecr2 is important for -H2AX formation and DSB repair. Therefore, our genome-wide screen identifies Cecr2 as a novel DNA damage response protein.

Adaptive lasso를 이용한 희박벡터자기회귀모형에서의 변수 선택

이슬기,백창룡,Lee, Sl Gi,Baek, Changryong 한국통계학회 2016 응용통계연구 Vol.29 No.1

본 논문은 다차원의 시계열 자료 분석에서 효율적인 희박벡터자기회귀모형에서의 모수 추정에 대해서 연구한다. 희박벡터자기회귀모형은 영에 가까운 계수를 정확이 영으로 둠으로써 희박성을 확보한다. 따라서 변수 선택과 모수 추정을 한꺼번에 할 수 있는 lasso를 이용한 방법론을 희박벡터자기회귀모형의 추정에 쓸 수 있다. 하지만 Davis 등(2015)에서는 모의실험을 통해 일반적인 lasso의 경우 영이아닌 계수를 참값보다 훨씬 더 많이 찾아 희박성에 약점이 있음을 보고하였다. 이에 따라 본 연구는 희박벡터자기회귀모형에 adaptive lasso를 이용하면 일반 lasso보다 희박성을 비롯한 전반적인 모수의 추정이 매우 유의하게 개선됨을 보인다. 또한 adaptive lasso에서 쓰이는 튜닝 모수들에 대한 선택도 아울러 논의한다. This paper considers variable selection in the sparse vector autoregressive (sVAR) model where sparsity comes from setting small coefficients to exact zeros. In the estimation perspective, Davis et al. (2015) showed that the lasso type of regularization method is successful because it provides a simultaneous variable selection and parameter estimation even for time series data. However, their simulations study reports that the regular lasso overestimates the number of non-zero coefficients, hence its finite sample performance needs improvements. In this article, we show that the adaptive lasso significantly improves the performance where the adaptive lasso finds the sparsity patterns superior to the regular lasso. Some tuning parameter selections in the adaptive lasso are also discussed from the simulations study.