• Journal of Ginseng Research
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• v.47 no.4
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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.

• Journal of the Korean Academy of Esthetic Dentistry
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• v.13 no.2
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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.

• Biomedical Science Letters
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• v.24 no.4
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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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• v.21 no.4
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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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• v.25 no.1
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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.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.4
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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.

• Journal of Life Science
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• v.22 no.7
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• pp.904-911
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• 2012

Yacon has been used in folk medicines as a medicinal tea for hypoglycemia treatment. In a recent study described herein, antioxidative, antibacterial, antifungal activities, and cell-protective functions of yacon leaves have been reported. To evaluate the effects on fibrosis on pancreatitis, the efficacy of 1% of yacon extract (YE) on dibutyltin dichloride (DBTC) (8 mg/kg)-induced pancreatitis in rats was examined. On the 21st day after the DBTC treatment, a large increase in collagen was observed in the pancreas in the DBTC-treatment group (DT). But this was noticeably decreased with YE. In relation to the expression of COX-2, there was no response or a very weak response in the pancreas of the control group (CON). However, in DT, strong expression of COX-2 was observed in the pancreas on the 14th day, and COX-2 was present in inflammatory cells in the pancreas of the DT, especially on the 21st day. The expression was decreased for YE compared with DT. A remarkable increase in TGF-${\beta}1$ expression was observed in inflammatory cells in the pancreas in DT on the 21st day, whereas the expression was not found in YE after 21 days. However, on the 21th day, TGF-${\beta}1$ expression was increased in acinar cells of YE compared with DT. VEGF expression was very similar to the expression of in the pancreas. These results suggest that YE has an inhibitory effect on DBTC-induced pancreatic fibrosis.

• BMB Reports
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• v.45 no.7
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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.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.2
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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.

• Proceedings of the PSK Conference
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• 2001.04a
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• pp.98-98
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• 2001