• Journal of Ginseng Research
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• 제47권4호
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• pp.534-542
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• 2023

Background: Ginsenoside Rg1, a bioactive component of Ginseng, has demonstrated anti-inflammatory, anti-cancer, and hepatoprotective effects. It is known that the epithelial-mesenchymal transition (EMT) plays a key role in the activation of hepatic stellate cells (HSCs). Recently, Rg1 has been shown to reverse liver fibrosis by suppressing EMT, although the mechanism of Rg1-mediated anti-fibrosis effects is still largely unclear. Interestingly, Smad7, a negative regulator of the transforming growth factor β (TGF-β) pathway, is often methylated during liver fibrosis. Whether Smad7 methylation plays a vital role in the effects of Rg1 on liver fibrosis remains unclear. Methods: Anti-fibrosis effects were examined after Rg1 processing in vivo and in vitro. Smad7 expression, Smad7 methylation, and microRNA-152 (miR-152) levels were also analyzed. Results: Rg1 significantly reduced the liver fibrosis caused by carbon tetrachloride, and reduced collagen deposition was also observed. Rg1 also contributed to the suppression of collagenation and HSC reproduction in vitro. Rg1 caused EMT inactivation, reducing Desmin and increasing E-cadherin levels. Notably, the effect of Rg1 on HSC activation was mediated by the TGF-β pathway. Rg1 induced Smad7 expression and demethylation. The over-expression of DNA methyltransferase 1 (DNMT1) blocked the Rg1-mediated inhibition of Smad7 methylation, and miR-152 targeted DNMT1. Further experiments suggested that Rg1 repressed Smad7 methylation via miR-152-mediated DNMT1 inhibition. MiR-152 inhibition reversed the Rg1-induced promotion of Smad7 expression and demethylation. In addition, miR-152 silencing led to the inhibition of the Rg1-induced EMT inactivation. Conclusion: Rg1 inhibits HSC activation by epigenetically modulating Smad7 expression and at least by partly inhibiting EMT.

• 대한심미치과학회지
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• 제13권2호
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• pp.7-11
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• 2004

The Schwachman-Diamond syndrome is an autosomal recessive syndrome(1/20,000 births), consisting of pancreatic insufficiency, neutopenia, which may be intermittent, neutrophil chemotaxis defects, metaphyseal dysostosis, failure to thrive and short stature. Patients present in infancy with poor growth and grease, foul-smelling stools that are characteristic of malabsorption. These children can be readily differentiated from those with cystic fibrosis by their normal sweat chloride levels, lack of the cystic fibrosis gene, and characteristic metaphyseal lesions. Pathologically, the pancreatic acini are replaced by fat with little fibrosis. The neutropenia may be cyclic. Recurrent pyogenic infections otitis media, pneumonia, dermatitis(fig 1), sepsis are common and a frequent cause of death. In dental examination, these patients had a poor oral hygine and moderate generalized marginal gingivitis, also show delayed primary tooth exfoliation and oral development. This report illustrates a case that pancreatic agenesis 6 yeas-old boy with various esthetic dental problems has been served the esthetic dental restoration of 6 years.

• 대한의생명과학회지
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• 제24권4호
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• pp.341-348
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• 2018

The polyherbal drug Gyeongshingangjeehwan 18 (GGEx18) from Rheum palmatum L. (Polygonaceae), Laminaria japonica Aresch (Laminariaceae), and Ephedra sinica Stapf (Ephedraceae) has traditionally been used as an antiobesity drug in Korean local clinics. This study investigates the effects of GGEx18 on pancreatic fibroinflammation in high-fat diet (HFD)-fed obese C57BL/6J mice and the molecular mechanism involved in this process. After HFD-fed obese C57BL/6J mice were treated with GGEx18 (125, 250, and 500 mg/kg) for 12 weeks, variables and determinants of obesity, pancreatic inflammation, and fibrosis were measured using histology, immunohistochemistry, and real-time polymerase chain reaction. Administration of GGEx18 at 500 mg/kg/day to obese mice decreased body weight gain, mesenteric adipose tissue mass, and adipocyte size. GGEx18 treatment not only reduced mast cells and CD68-immunoreactive cells, but also decreased collagen levels and ${\alpha}$-smooth muscle actin-positive cells in the pancreas of HFD-fed mice. Concomitantly, GGEx18 decreased the expression of genes for inflammation (i.e., CD68 and tumor necrosis factor ${\alpha}$) and fibrosis (i.e., collagen ${\alpha}1$ and transforming growth factor ${\beta}$) in the pancreas of obese mice. These results suggest that GGEx18 may inhibit visceral obesity and related pancreatic fibroinflammation in HFD-fed obese mice.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제21권4호
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• pp.306-314
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• 2018

Purpose: The objective of this study was to describe the clinical phenotypes of children and adolescents with cystic fibrosis (CF); and to assess the role of pancreatic insufficiency and neonatal screening in diagnosis. Methods: A cross-sectional study was conducted, which included 77 patients attending a reference center of CF between 2014 and 2016. Epidemiological data, anthropometric measurements, and the presence of pulmonary, pancreatic, gastrointestinal and hepatobiliary manifestations were evaluated based on clinical data and complementary examinations. Results: Of the 77 patients, 51.9% were male, with a median age of 147 months (7.0-297.0 months), and the majority showed adequate nutritional status. The most common phenotype was pulmonary (92.2%), followed by pancreatic (87.0%), with pancreatic insufficiency in most cases. Gastrointestinal manifestation occurred in 46.8%, with constipation being the more common factor. Hepatobiliary disease occurred in 62.3% of patients. The group with pancreatic insufficiency was diagnosed earlier (5.0 months) when compared to the group with sufficiency (84.0 months) (p=0.01). The age of diagnosis was reduced following implementation of neonatal screening protocols for CF (6.0 months before vs. 3.0 months after, p=0.02). Conclusion: The pulmonary phenotype was the most common, although extrapulmonary manifestations were frequent and clinically relevant, and should mandate early detection and treatment. Neonatal screening for CF led to earlier diagnosis in patients with pancreatic failure, and therefore, should be adopted universally.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제25권1호
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• pp.1-12
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• 2022

Inflammation plays an important role in the outcome of patients with cystic fibrosis (CF). It may develop due to cystic fibrosis transmembrane conductance regulator protein dysfunction, pancreatic insufficiency, or prolonged pulmonary infection. Fecal calprotectin (FC) has been used as a noninvasive method to detect inflammation. Therefore, the aim of the current meta-analysis was to investigate the relationship between FC and phenotype severity in patients with CF. In this study, searches were conducted in PubMed, Science Direct, Scopus, and Embase databases up to August 2021 using terms such as "cystic fibrosis," "intestine," "calprotectin," and "inflammation." Only articles published in English and human studies were selected. The primary outcome was the level of FC in patients with CF. The secondary outcome was the relationship between FC and clinical severity. Statistical analysis was performed using Comprehensive Meta-Analysis software. Of the initial 303 references, only six articles met the inclusion criteria. The mean (95% confidence interval [CI]) level of FC was 256.5 mg/dL (114.1-398.9). FC levels were significantly associated with pancreatic insufficiency (mean, 243.02; 95% CI, 74.3 to 411.6; p=0.005; I²=0), pulmonary function (r=-0.39; 95% CI, -0.58 to -0.15; p=0.002; I²=60%), body mass index (r=-0.514; 95% CI, 0.26 to 0.69; p<0.001; I²=0%), and Pseudomonas colonization (mean, 174.77; 95% CI, 12.5 to 337.02; p=0.035; I²=71%). While FC is a reliable noninvasive marker for detecting gastrointestinal inflammation, it is also correlated with the severity of the disease in patients with CF.

• 한국간담췌외과학회지
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• 제26권4호
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• pp.325-332
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• 2022

Backgrounds/Aims: To analyze relationships of hepatic histopathological findings and bile microbiological profiles with perioperative outcomes and risk of late biliary stricture in individuals undergoing surgical bile duct injury (BDI) repair. Methods: A historical cohort study was carried out at a tertiary university hospital. Fifty-six individuals who underwent surgical BDI repair from 2014-2018 with a minimal follow-up of 24 months were enrolled. Liver biopsies were performed to analyze histopathology. Bile samples were collected during repair procedures. Hepatic histopathological findings and bile microbiological profiles were then correlated with perioperative and late outcomes through uni- and multi-variate analyses. Results: Forty-three individuals (76.8%) were females and average age was 47.2 ± 13.2 years; mean follow-up was 38.1 ± 18.6 months. The commonest histopathological finding was hepatic fibrosis (87.5%). Bile cultures were positive in 53.5%. The main surgical technique was Roux-en-Y hepaticojejunostomy (96.4%). Overall morbidity was 35.7%. In univariate analysis, liver fibrosis correlated with the duration of the operation (R = 0.3; p = 0.02). In multivariate analysis, fibrosis (R = 0.36; p = 0.02) and cholestasis (R = 0.34; p = 0.02) independently correlated with operative time. Strasberg classification independently correlated with estimated bleeding (R = 0.31; p = 0.049). The time elapsed between primary cholecystectomy and BDI repair correlated with hepatic fibrosis (R = 0.4; p = 0.01). Conclusions: Bacterial contamination of bile was observed in most cases. The degree of fibrosis and cholestasis correlated with operative time. The waiting time for definitive repair correlated with the severity of liver fibrosis.

• 생명과학회지
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• 제22권7호
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• pp.904-911
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• 2012

야콘(Smallanthus sonchifolius)은 저혈당에 민간요법으로 이용해 오고 있는 구근작물이다. 최근에는 야콘잎이 항산화, 항균, 항진균 활성과 세포보호 기능이 있다고 보고되고 있다. 본 실험에서는 이러한 생리활성을 지니는 야콘잎을 이용하여 흰쥐에 DBTC (8 mg/kg)를 주사하여 췌장염을 유발시킨 후 1% 야콘추출물이 췌장의 섬유화에 미치는 영향을 연구하였다. 유발 21일째 처리군에서 췌장의 실질조직의 많은 부분이 collagen으로 재구성되어 있었으나 유발군에서는 처리군에 비해 현저히 감소되어 있었다. COX-2 발현에서, 대조군은 반응이 나타나지 않거나 매우 약한 반응이었으나, 유발군에서는 14일째 매우 증가되었으며, 특히 21일째는 침윤하고 있는 많은 염증세포에서 COX-2의 발현이 확인되었다. 처리군은 유발군에 비해 발현이 감소되었다. TGF-${\beta}1$ 발현은 21일째 염증세포에서는 유발군이 처리군에 비해 현저한 증가 현상이 나타났으나, 샘꽈리세포에서의 TGF-${\beta}1$의 발현은 처리군에서 증가되었다. VEGF 발현은 TGF-${\beta}1$의 발현과 거의 유사한 경향으로 나타났다. 그러므로 야콘추출물이 DBTC로 유도된 췌장염의 섬유화 진행을 억제하는데 매우 효과적임을 확인하였다.

• BMB Reports
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• 제45권7호
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• pp.402-407
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• 2012

Nardostachys jatamansi (NJ) belonging to the Valerianaceae family has been used as a remedy for gastrointestinal inflammatory diseases for decades. However, the potential for NJ to ameliorate alcoholic chronic pancreatitis (ACP) is unknown. The aim of this study was to examine the inhibitory effects of NJ on ACP. C57black/6 mice received ethanol injections intraperitoneally for 3 weeks against a background of cerulein-induced acute pancreatitis. During ACP, NJ was ad libitum administrated orally with water. After 3 weeks of treatment, the pancreas was harvested for histological examination. NJ treatment increased the pancreatic acinar cell survival (confirmed by amylase level testing) and reduced collagen deposition and pancreatic stellate cell (PSC) activation. In addition, NJ treatment reduced the activation but not death of PSC. In conclusion, our results suggest that NJ attenuated ACP through the inhibition of PSC activation.

• 한국간담췌외과학회지
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• 제26권2호
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• pp.178-183
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• 2022

Backgrounds/Aims: Proximal splenorenal shunt (PSRS) is considered a one-time treatment for noncirrhotic portal hypertension (NCPH) to prevent recurrent upper gastrointestinal (UGI) hemorrhage and long-term complications. Long-term shunt patency is necessary to achieve these. The lie of the shunt is a contributing factor to early shunt thrombosis. We investigated the role of resection of the distal tail of pancreas (caudal pancreatectomy [CP]) in improving the lie of shunt and decreasing shunt thrombosis. Methods: This was a retrospective cohort study of patients with NCPH who underwent PSRS between 2014-2020 in JIPMER, Puducherry, India. CP was performed in patients with a long tail of pancreas, with the tip of pancreatic tail extending up to splenic hilum on preoperative CT. Perioperative parameters and shunt patency rate of patients who underwent PSRS with CP (Group A) were compared with patients undergoing conventional PSRS (Group B). Statistical analysis was performed using the Mann-Whitney U test and χ² test. Results: Eighty four patients with NCPH underwent PSRS (extrahepatic portal vein obstruction = 39; noncirrhotic portal fibrosis = 45). Blood loss was lower (p = 0.002) and post-shunt fall in portal pressure higher (p = 0.002) in Group A. Shunt thrombosis rate was lower (p = 0.04) while rate of complete variceal regression (p = 0.03) and biochemical pancreatic leak (p = 0.01) were higher in Group A.There was no clinically relevant pancreatic fistula in either group. Conclusions: CP is a safe and useful technique for reducing shunt thrombosis after PSRS in patients with NCPH by improving the lie of shunt.

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of the Pharmaceutical Society of Korea
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• pp.98-98
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• 2001