• Journal of the Korean Society of Radiology
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• v.81 no.2
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• pp.365-378
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• 2020

Purpose This study was performed to determine whether the T1 relaxation time of gadoxetic acid-enhanced liver MR imaging is useful for detecting and staging liver fibrosis in patients with chronic liver disease. Materials and Methods One hundred and three patients with suspected focal liver lesion underwent MR imaging and Fibroscan. Fibroscan was chosen as the reference standard for classifying liver fibrosis. T1 relaxation times were acquired before (preT1), 20 minutes after (postT1) contrast administration, and reduction rate of T1 relaxation time (rrT1) on transverse 3D VIBE (volumetric interpolated breath-hold examination) sequence using 3T MR imaging. The optimal cut-off values for the fibrosis staging were determined with ROC analysis. Results PreT1 and postT1 increased and rrT1 decreased constantly with increasing severity of liver fibrosis according to the METAVIR score (F0-F4). There were statistically significant differences between F2 and F3 in preT1 (F2, 836.0 ± 74.7 ms; F3, 888.6 ± 77.5 ms, p < 0.05) and between F3 and F4 in postT1 (F3, 309.0 ± 80.2 ms; F4, 406.6 ± 147.7 ms, p < 0.05) and rrT1 (F3, 65.4 ± 7.7%; F4, 57.3 ± 11.4%, p < 0.05). ROC analysis revealed that combination test (preT1 + postT1) was the best test for predicting liver fibrosis. Conclusion PreT1 and postT1 increased constantly with increasing severity of liver fibrosis. T1 mapping in gadoxetic acid-enhanced liver MR imaging could be a helpful complementary sequence to determine the liver fibrosis stage.

• Molecules and Cells
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• v.46 no.1
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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.

• Journal of Biomedical Engineering Research
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• v.41 no.1
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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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• v.10 no.1
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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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• v.15 no.6
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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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• v.79 no.4
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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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• v.21 no.1
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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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• v.14 no.1
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• pp.74-80
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• 2011

Purpose: Based on previous research findings, it is well-known that the timing of surgery is generally considered the most important prognostic factor for a Kasai portoenterostomy, the primary treatment for biliary atresia. This research aimed to identify the optimal timing of a Kasai portoenterostomy and to verify if the proposed optimal timing corresponds to previous studies. All patients were classified by the timing of surgery, and pre- and post-operative fibrotic changes of the liver were measured with the elasticity value from fibroscans. Methods: The stiffness scores of the pre- and post-operative fibroscans in 34 patients who were treated by Kasai portoenterostomy from October 2007 to September 2010 in Severance children's hospital were reviewed. Results: The earlier the patients were treated by Kasai portoenterostomy, the lower the fibroscan scores. When the patients were treated prior to the 8th week, the post-operative scores of the fibroscans were significantly better than those patients who were treated after the 8th week, and some even recovered partially. Moreover, when operated before the 8th week, the differences between each pre- and postoperative fibroscan score also showed statistical relevance (p=0.0002). Conclusion: The earlier the patient was treated by Kasai portoenterostomy, the less liver fibrosis that developed, the lower the level of post-operative fibrosis, and the less the degree of fibrotic progress before and after the operation. Thus, this research proposal reconfirms once more that the 8th week is the optimal timing for a Kasai portoenterostomy.

• Proceedings of the Korean Society of Veterinary Pathology Conference
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• 2002.11a
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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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• v.24 no.5
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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.