• 대한영상의학회지
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• 제81권2호
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• pp.365-378
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• 2020

목적 본 연구는 gadoxetic acid 조영증강 간 자기공명영상에서 T1 이완시간이 만성간질환을 가진 환자에서 간섬유화의 발견과 병기설정에 유용한지 알아보고자 한다. 대상과 방법 국소간병변이 의심되는 103명 환자들이 간 자기공명영상과 Fibroscan을 시행하였다. Fibroscan은 간섬유화의 정도를 분류하는 참조표준검사로 사용되었다. T1 이완시간은 조영제 주입 전(preT1)과 주입 20분 후(postT1), 그리고 이들 간의 T1 이완시간 감소율(rrT1)을 3 테슬라 자기공명영상의 횡단 3D VIBE 시퀀스 하에 측정하였다. Receiver operating characteristic (이하 ROC) 분석을 통해 간섬유화 병기설정을 위한 최적의 cut-off 값이 결정되었다. 결과 METAVIR score (F0-F4)에 따른 간섬유화 병기가 증가함에 따라, preT1과 postT1은 증가하였고, rrT1은 감소하였다. PreT1의 F2와 F3 사이(F2, 836.0 ± 74.7 ms; F3, 888.6 ± 77.5 ms, p < 0.05), postT1의 F3와 F4 사이(F3, 309.0 ± 80.2 ms; F4, 406.6 ± 147.7 ms, p < 0.05), 그리고 rrT1의 F3와 F4사이(F3, 65.4 ± 7.7%; F4 57.3 ± 11.4%, p < 0.05)에서 통계적 유의미한 차이를 보였다. ROC 분석은 preT1과 postT1의 병용검사가 간섬유화 병기설정에 있어 가장 유용한 검사라는 것을 보여준다. 결론 preT1과 postT1은 간섬유화 병기가 증가함에 따라 증가하며, T1 mapping이 gadoxetic acid 조영증강 간 자기공명영상에서 간섬유화 병기설정에 있어 유용한 보조적 시퀀스로 사용될 수 있다.

• Molecules and Cells
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• 제46권1호
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• pp.10-20
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• 2023

Antisense oligonucleotide (ASO) technology has become an attractive therapeutic modality for various diseases, including Mendelian disorders. ASOs can modulate the expression of a target gene by promoting mRNA degradation or changing pre-mRNA splicing, nonsense-mediated mRNA decay, or translation. Advances in medicinal chemistry and a deeper understanding of post-transcriptional mechanisms have led to the approval of several ASO drugs for diseases that had long lacked therapeutic options. For instance, an ASO drug called nusinersen became the first approved drug for spinal muscular atrophy, improving survival and the overall disease course. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF). Although Trikafta and other CFTR-modulation therapies benefit most CF patients, there is a significant unmet therapeutic need for a subset of CF patients. In this review, we introduce ASO therapies and their mechanisms of action, describe the opportunities and challenges for ASO therapeutics for CF, and discuss the current state and prospects of ASO therapies for CF.

• 대한의용생체공학회:의공학회지
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• 제41권1호
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• pp.48-54
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• 2020

In this paper, we deal with a liver fibrosis classification problem using ultrasound B-mode images. Commonly representative methods for classifying the stages of liver fibrosis include liver biopsy and diagnosis based on ultrasound images. The overall liver shape and the smoothness and roughness of speckle pattern represented in ultrasound images are used for determining the fibrosis stages. Although the ultrasound image based classification is used frequently as an alternative or complementary method of the invasive biopsy, it also has the limitations that liver fibrosis stage decision depends on the image quality and the doctor's experience. With the rapid development of deep learning algorithms, several studies using deep learning methods have been carried out for automated liver fibrosis classification and showed superior performance of high accuracy. The performance of those deep learning methods depends closely on the amount of datasets. We propose an enhanced U-net architecture to maximize the classification accuracy with limited small amount of image datasets. U-net is well known as a neural network for fast and precise segmentation of medical images. We design it newly for the purpose of classifying liver fibrosis stages. In order to assess the performance of the proposed architecture, numerical experiments are conducted on a total of 118 ultrasound B-mode images acquired from 78 patients with liver fibrosis symptoms of F0~F4 stages. The experimental results support that the performance of the proposed architecture is much better compared to the transfer learning using the pre-trained model of VGGNet.

• Nutrition Research and Practice
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• 제10권1호
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• pp.33-41
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• 2016

BACKGROUND/OBJECTIVES: Diabetes mellitus (DM) is a major chronic disease which increases global health problems. Diabetes-induced renal damage is associated with inflammation and fibrosis. Alpha (AT) and gamma-tocopherols (GT) have shown antioxidant and anti-inflammatory effects in inflammation-mediated injuries. The primary aim of this study was to investigate effects of AT and GT supplementations on hyperglycemia induced acute kidney inflammation in alloxan induced diabetic mice with different levels of fasting blood glucose (FBG). MATERIALS/METHODS: Diabetes was induced by injection of alloxan monohydrate (150 mg/kg, i.p) in ICR mice (5.5-week-old, male) and mice were subdivided according to their FBG levels and treated with different diets for 2 weeks; CON: non-diabetic mice, m-DMC: diabetic control mice with mild FBG levels (250 mg/dl ${\leq}$ FBG ${\leq}$ 450 mg/dl), m-AT: m-DM mice fed AT supplementation (35 mg/kg diet), m-GT: m-DM mice with GT supplementation (35 mg/kg diet), s-DMC: diabetic control mice with severe FBG levels (450 mg/dl < FBG), s-AT: s-DM mice with AT supplementation, s-GT: s-DM mice with GT supplementation. RESULTS: Both AT and GT supplementations showed similar beneficial effects on $NF{\kappa}B$ associated inflammatory response (phosphorylated inhibitory kappa B-${\alpha}$, interleukin-$1{\beta}$, C-reactive protein, monocyte chemotactic protein-1) and pre-fibrosis (tumor growth factor ${\beta}$-1 and protein kinase C-II) as well as an antioxidant emzyme, heme oxygenase-1 (HO-1) in diabetic mice. On the other hands, AT and GT showed different beneficial effects on kidney weight, FBG, and oxidative stress associated makers (malondialdehyde, glutathione peroxidase, and catalase) except HO-1. In particular, GT significantly preserved kidney weight in m-DM and improved FBG levels in s-DM and malondialdehyde and catalase in m- and s-DM, while AT significantly attenuated FBG levels in m-DM and improved glutathione peroxidase in m- and s-DM. CONCLUSIONS: the results suggest that AT and GT with similarities and differences would be considered as beneficial nutrients to modulate hyperglycemia induced acute renal inflammation. Further research with careful approach is needed to confirm beneficial effects of tocopherols in diabetes with different FBG levels for clinical applications.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2405-2425
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• 2014

Radiation exposure leads to several pathophysiological conditions, including oxidative damage, inflammation and fibrosis, thereby affecting the survival of organisms. This review explores the radiation countermeasure properties of fourteen (14) plant extracts or plant-derived compounds against these cellular manifestations. It was aimed at evaluating the possible role of plants or its constituents in radiation countermeasure strategy. All the 14 plant extracts or compounds derived from it and considered in this review have shown some radioprotection in different in vivo, ex-vivo and or in vitro models of radiological injury. However, few have demonstrated advantages over the others. C. majus possessing antioxidant, anti-inflammatory and immunomodulatory effects appears to be promising in radioprotection. Its crude extracts as well as various alkaloids and flavonoids derived from it, have shown to enhance survival rate in irradiated mice. Similarly, curcumin with its antioxidant and the ability to ameliorate late effect of radiation exposure, combined with improvement in survival in experimental animal following irradiation, makes it another probable candidate against radiological injury. Furthermore, the extracts of P. hexandrum and P. kurroa in combine treatment regime, M. piperita, E. officinalis, A. sinensis, nutmeg, genistein and ginsan warrants further studies on their radioprotective potentials. However, one that has received a lot of attention is the dietary flaxseed. The scavenging ability against radiation-induced free radicals, prevention of radiation-induced lipid peroxidation, reduction in radiation cachexia, level of inflammatory cytokines and fibrosis, are some of the remarkable characteristics of flaxseed in animal models of radiation injury. While countering the harmful effects of radiation exposure, it has shown its ability to enhance survival rate in experimental animals. Further, flaxseed has been tested and found to be equally effective when administered before or after irradiation, and against low doses (${\leq}5Gy$) to the whole body or high doses (12-13.5 Gy) to the whole thorax. This is particularly relevant since apart from the possibility of using it in pre-conditioning regime in radiotherapy, it could also be used during nuclear plant leakage/accidents and radiological terrorism, which are not pre-determined scenarios. However, considering the infancy of the field of plant-based radioprotectors, all the above-mentioned plant extracts/plant-derived compounds deserves further stringent study in different models of radiation injury.

• Tuberculosis and Respiratory Diseases
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• 제79권4호
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• pp.257-266
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• 2016

Background: Idiopathic pulmonary fibrosis is a common interstitial lung disease; it is a chronic, progressive, and fatal lung disease of unknown etiology. Over the last two decades, knowledge about the underlying mechanisms of pulmonary fibrosis has improved markedly and facilitated the identification of potential targets for novel therapies. However, despite the large number of antifibrotic drugs being described in experimental pre-clinical studies, the translation of these findings into clinical practices has not been accomplished yet. NADH:quinone oxidoreductase 1 (NQO1) is a homodimeric enzyme that catalyzes the oxidation of NADH to $NAD^+$ by various quinones and thereby elevates the intracellular $NAD^+$ levels. In this study, we examined the effect of increase in cellular $NAD^+$ levels on bleomycin-induced lung fibrosis in mice. Methods: C57BL/6 mice were treated with intratracheal instillation of bleomycin. The mice were orally administered with ${\beta}$-lapachone from 3 days before exposure to bleomycin to 1-3 weeks after exposure to bleomycin. Bronchoalveolar lavage fluid (BALF) was collected for analyzing the infiltration of immune cells. In vitro, A549 cells were treated with transforming growth factor ${\beta}1$ (TGF-${\beta}1$) and ${\beta}$-lapachone to analyze the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT). Results: ${\beta}$-Lapachone strongly attenuated bleomycin-induced lung inflammation and fibrosis, characterized by histological staining, infiltrated immune cells in BALF, inflammatory cytokines, fibrotic score, and TGF-${\beta}1$, ${\alpha}$-smooth muscle actin accumulation. In addition, ${\beta}$-lapachone showed a protective role in TGF-${\beta}1$-induced ECM expression and EMT in A549 cells. Conclusion: Our results suggest that ${\beta}$-lapachone can protect against bleomycin-induced lung inflammation and fibrosis in mice and TGF-${\beta}1$-induced EMT in vitro, by elevating the $NAD^+$/NADH ratio through NQO1 activation.

• Journal of Chest Surgery
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• 제21권1호
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• pp.1-9
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• 1988

The left atrial [LA] dimension and atrial fibrillation [AF] in patients with mitral valvular heart diseases have been thought to be related to hemodynamic burden to the LA depending on severity of stenosis or regurgitation of mitral valve, left ventricular contractility and the heart conditions. If hemodynamic burden persists long, it can affect the LA wall and structural change of the LA wall itself can developed. So the structural change of the LA wall could be thought to be related to the LA dimension and AF. To verify this relation, the LA wall biopsy was performed in 26 patients with rheumatic mitral valvular heart disease at the left atriotomy incision margin which was posterior to the interatrial groove after completion of surgery to the mitral valve such as valve replacement or commissurotomy. Relation of the pathological state of the LA wall to AF and the LA dimension measured by M-mode echocardiography was studied. The conclusions were as follow. 1. There was tendency that degree of fibrosis of myocardium of the LA wall was related to the LA dimension. 2. There was more chance that patients who had severe fibrosis of myocardium of the LA wall had pre and postoperative AF. 3. There was no relation between reduction rate of the LA dimension before and after surgery and degree of fibrosis of myocardium of the LA wall.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제14권1호
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• pp.74-80
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• 2011

목 적: 선천성 담도폐쇄증의 일차적 치료로 알려진 Kasai 수술에서의 가장 중요한 예후 인자로 수술 시기가 중요하다는 것은 기존의 연구 결과들을 통해 잘 알려져 있다. 본 연구에서는 선천성 담도 폐쇄증 환아들을 수술 시기별로 분류하고 간섬유화 스캔을 수술 전후에 시행하여 얻어진 간탄성률값을 이용하여 수술 전후의 간 섬유화 변화를 비교함으로서 본 연구에서 도출된 최적의 수술시기가 기존의 연구와 일치하는지 재확인 하고자 한다. 방 법: 2007년 10월부터 2010년 7월까지 단일 기관에서 Kasai 수술을 시행 받은 환자 중, 수술 전후로 간섬유화 스캔을 시행한 환자 34명을 대상으로 수술 시기별 간탄성률 결과값을 비교하였다. 결 과: 환자군의 수술 시기가 빠를수록 수술 전과 후 모두에서 간탄성률 결과값은 좋았고, 특히 8주 이전에 수술을 시행 받은 경우 그 이상에서 수술을 받은 환자군보다 수술 후의 간섬유화가 적게 진행되었고 일부에서는 회복되었다. 또한 8주 수술 전후의 각 탄성률 간의 차이값 또한 통계적으로 유의하였다. 결 론: Kasai 수술의 시기가 이를수록 수술 전 간 섬유화가 적고, 적어도 8주 이전에서 Kasai 수술을 시행하였을 때 수술 이후의 간섬유화가 양호하였으며 수술전후의 간섬유화 진행 정도가 크지 않았다. 따라서 본 연구에서는 간섬유화스캔을 바탕으로 적어도 8주 미만의 연령이 Kasai 수술을 시행 받기에 최적의 시기임을 재확인하였다.

• 한국수의병리학회:학술대회논문집
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• 한국수의병리학회 2002년도 추계학술대회초록집
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• pp.9-9
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• 2002

Grossly, the liver exhibits marked cirrhotic changes characteristics of the pre-transformation phase of WHV. Microscopically, focal hepatocyte necrosis and inflammatory cells were observed in midzonal and periportal areas. Bridging portal fibrosis produced pseudolobulation due to entrapment of hyperplastic hepatocytes. Biliary hyperplasia, ductal cell proliferation, and increased amounts of fibrous connective tissue expanded portal areas and extended into periportal areas. Myofibroblasts stained positive for -SMA were detected in proliferating fibrotic tissue and sinusoids.

• Korean Journal of Radiology
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• 제24권5호
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• pp.465-475
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• 2023

Objective: To evaluate the feasibility of ultrasound shear wave elastography (SWE) for predicting hepatic fibrosis and native liver outcomes in patients with biliary atresia. Materials and Methods: This prospective study included 33 consecutive patients with biliary atresia (median age, 8 weeks [interquartile range, 6-10 weeks]; male:female ratio, 15:18) from Severance Children's Hospital between May 2019 and February 2022. Preoperative (within 1 week from surgery) and immediate postoperative (on postoperative days [PODs] 3, 5, and 7) ultrasonographic findings were obtained and analyzed, including the SWE of the liver and spleen. Hepatic fibrosis, according to the METAVIR score at the time of Kasai portoenterostomy and native liver outcomes during postsurgical follow-up, were compared and correlated with imaging and laboratory findings. Poor outcomes were defined as intractable cholangitis or liver transplantation. The diagnostic performance of SWE in predicting METAVIR F3-F4 and poor hepatic outcomes was analyzed using receiver operating characteristic (ROC) analyses. Results: All patients were analyzed without exclusion. Perioperative advanced hepatic fibrosis (F3-F4) was associated with older age and higher preoperative direct bilirubin and SWE values in the liver and spleen. Preoperative liver SWE showed a ROC area of 0.806 and 63.6% (7/11) sensitivity and 86.4% (19/22) specificity at a cutoff of 17.5 kPa for diagnosing F3-F4. The poor outcome group included five patients with intractable cholangitis and three undergoing liver transplantation who showed high postoperative liver SWE values. Liver SWE on PODs 3-7 showed ROC areas of 0.783-0.891 for predicting poor outcomes, and a cutoff value of 10.3 kPa for SWE on POD 3 had 100% (8/8) sensitivity and 73.9% (17/23) specificity. Conclusion: Preoperative liver SWE can predict advanced hepatic fibrosis, and immediate postoperative liver SWE can predict poor native liver outcomes in patients with biliary atresia.