Background: Nonalcoholic steatohepatitis (NASH) is a liver disease caused by obesity that leads to hepatic lipoapoptosis, resulting in fibrosis and cirrhosis. However, the mechanism underlying NASH is largely unknown, and there is currently no effective therapeutic agent against it. DWN12088, an agent used for treating idiopathic pulmonary fibrosis, is a selective prolyl-tRNA synthetase (PRS) inhibitor that suppresses the synthesis of collagen. However, the mechanism underlying the hepatoprotective effect of DWN12088 is not clear. Therefore, we investigated the role of DWN12088 in NASH progression. Methods: Mice were fed a chow diet or methionine-choline deficient (MCD)-diet, which was administered with DWN12088 or saline by oral gavage for 6 weeks. The effects of DWN12088 on NASH were evaluated by pathophysiological examinations, such as real-time quantitative reverse transcription polymerase chain reaction, immunoblotting, biochemical analysis, and immunohistochemistry. Molecular and cellular mechanisms of hepatic injury were assessed by in vitro cell culture. Results: DWN12088 attenuated palmitic acid (PA)-induced lipid accumulation and lipoapoptosis by downregulating the Rho-kinase (ROCK)/AMP-activated protein kinase (AMPK)/sterol regulatory element-binding protein-1c (SREBP-1c) and protein kinase R-like endoplasmic reticulum kinase (PERK)/α subunit of eukaryotic initiation factor 2 (eIF2α)/activating transcription factor 4 (ATF4)/C/EBP-homologous protein (CHOP) signaling cascades. PA increased but DWN12088 inhibited the phosphorylation of nuclear factor-κB (NF-κB) p65 (Ser536, Ser276) and the expression of proinflammatory genes. Moreover, the DWN12088 inhibited transforming growth factor β (TGFβ)-induced pro-fibrotic gene expression by suppressing TGFβ receptor 1 (TGFβR1)/Smad2/3 and TGFβR1/glutamyl-prolyl-tRNA synthetase (EPRS)/signal transducer and activator of transcription 6 (STAT6) axis signaling. In the case of MCD-diet-induced NASH, DWN12088 reduced hepatic steatosis, inflammation, and lipoapoptosis and prevented the progression of fibrosis. Conclusion Our findings provide new insights about DWN12088, namely that it plays an important role in the overall improvement of NASH. Hence, DWN12088 shows great potential to be developed as a new integrated therapeutic agent for NASH.

Purpose: Among the characteristics of non-alcoholic fatty liver disease (NAFLD), hepatic steatosis is due to excessive fat accumulation and causes liver damage and lipotoxicity, which are associated with insulin resistance, endoplasmic reticulum (ER) stress, and apoptosis. Umbelliferone (UMB) has various powerful pharmacological properties, such as antioxidant, anti-hyperglycemic, anti-viral, and anti-inflammatory effects. However, the mechanism of action in hepatic steatosis and lipid-induced ER stress is still unclear. Thus, the efficacy of UMB in hepatic steatosis and palmitate (PA)-induced hepatocellular lipotoxicity was evaluated in the present study. Materials and Methods: Male C57BL/6J mice (n=40) were divided into four groups: regular diet (RD), UMB-supplemented RD, high-fat diet (HFD), and UMB-supplemented HFD. All mice were fed orally for 12 weeks. In addition, the effects of UMB on lipotoxicity were investigated in AML12 cells treated with PA (250 μM) for 24 h; Western blot analysis was used to evaluate the changes in ER stress and apoptotic-associated proteins. Results: Administration with UMB in HFD-fed mice reduced lipid accumulation and hepatic triglyceride (TG) as well as serum insulin and glucose levels. In AML12 cells, UMB treatment reduced lipid accumulation as indicated by decreases in the levels of lipogenesis markers, such as SREBP1, FAS, PPAR-γ, and ADRP. Furthermore, UMB reduced both oxidative stress and ER stress-related cellular apoptosis. Conclusion UMB supplementation ameliorated hepatic steatosis and improved insulin resistance by inhibiting lipid accumulation and regulating ER stress. These findings strongly suggest that UMB may be a potential therapeutic compound against NAFLD.

Background: Curcumin 2005-8 (Cur5-8), a derivative of curcumin, improves fatty liver disease via AMP-activated protein kinase activation and autophagy regulation. EW-7197 (vactosertib) is a small molecule inhibitor of transforming growth factor β (TGF-β) receptor I and may scavenge reactive oxygen species and ameliorate fibrosis through the SMAD2/3 canonical pathway. This study aimed to determine whether co-administering these two drugs having different mechanisms is beneficial. Methods: Hepatocellular fibrosis was induced in mouse hepatocytes (alpha mouse liver 12 [AML12]) and human hepatic stellate cells (LX-2) using TGF-β (2 ng/mL). The cells were then treated with Cur5-8 (1 μM), EW-7197 (0.5 μM), or both. In animal experiments were also conducted during which, methionine-choline deficient diet, Cur5-8 (100 mg/kg), and EW-7197 (20 mg/kg) were administered orally to 8-week-old C57BL/6J mice for 6 weeks. Results: TGF-β-induced cell morphological changes were improved by EW-7197, and lipid accumulation was restored on the administration of EW-7197 in combination with Cur5-8. In a nonalcoholic steatohepatitis (NASH)-induced mouse model, 6 weeks of EW-7197 and Cur5-8 co-administration alleviated liver fibrosis and improved the nonalcoholic fatty liver disease (NAFLD) activity score. Conclusion Co-administering Cur5-8 and EW-7197 to NASH-induced mice and fibrotic hepatocytes reduced liver fibrosis and steatohepatitis while maintaining the advantages of both drugs. This is the first study to show the effect of the drug combination against NASH and NAFLD. Similar effects in other animal models will confirm its potential as a new therapeutic agent.

BACKGROUND/AIMS: Age, sex, gene and life style are modulating risks for colon cancer. Although alcohol intake may impact on colorectal adenoma, clear association has not been established yet. We aimed to investigate effects of alcohol consumption on the characteristics of colorectal adenoma. METHODS: Patients who underwent colonoscopic polypectomy of colorectal adenoma in the department of gastroenterology of Eulji hospital through 2005 to 2012, having both blood tests and ultrasound or abdominal CT examination were enrolled. The alcohol drinking patients were subdivided into normal or abnormal laboratory group, and alcoholic liver diseases group. RESULTS: 212 patients with colorectal adenoma were analyzed; advanced adenoma and multiple adenoma were found in 68 (32.0%) and 79 (37.2%) patients. When compared to the nondrinker group (120/212 patients), the alcohol drinker group (92/212 patients) represented significantly high odds ratios (ORs) for advanced adenoma (OR, 2.697; P=0.002), and multiple adenoma (OR, 1.929; P=0.039). Among alcohol drinker (92 patients), the ORs of advanced adenoma were 6.407 (P=0.003) in alcoholic liver diseases group (17 patients), 3.711 (P=0.002) in the alcohol drinker with abnormal lab (24 patients), and 2.184 (P=0.034), in the alcohol drinker with normal lab (51 patients) compared to nondrinker group. CONCLUSIONS: This study showed that alcohol drinking may influence on the development of advanced colorectal adenoma and multiplicity. Especially in the group with alcoholic liver diseases and with abnormal lab presented significantly higher ORs of advanced adenoma.
Adenoma* ; Alcohol Drinking* ; Colonic Neoplasms ; Gastroenterology ; Hematologic Tests ; Humans ; Life Style ; Liver Diseases, Alcoholic ; Odds Ratio ; Tomography, X-Ray Computed ; Ultrasonography

BACKGROUND/AIMS: The relationship between Crohn's disease and gallstones is established. However, the prevalence and risk factors for gallstones in patients with ulcerative colitis (UC) are not yet well understood. The aim of this study was to evaluate the prevalence and risk factors of gallstones in patients with UC. METHODS: This study was a retrospective single center study. A total of 87 patients with UC and 261 healthy controls were enrolled. Age, sex, and body mass index were matched. To investigate risk factors, the extent of UC, duration of disease, number of hospital admissions, and number of steroid treatments in patients with UC were evaluated. RESULTS: The prevalence of gallstones in patients with UC was 13.8%, whereas that in healthy controls was only 3.1% (P<0.001). For patients with UC, patients > or =50 years of age had a 3.6-times higher risk of gallstones compared to that in those <50 years of age, and the difference was statistically significant (odds ratio, 3.60; confidence interval, 1.03-12.61) in univariate analysis. There were no statistically significant disease-related risk factors for gallstones in UC patients. CONCLUSIONS: This is the first study of gallstone prevalence in Korean UC patients. In this study, patients with UC had a higher prevalence of gallstones compared to that in well-matched healthy controls. Age seemed to be a possible risk factor, and more studies are needed. Further prospective, large-scale studies will be required to confirm the risk factors for gallstones in UC patients.
Asymptomatic Diseases ; Body Mass Index ; Colitis, Ulcerative* ; Crohn Disease ; Gallstones* ; Humans ; Prevalence ; Retrospective Studies ; Risk Factors

BACKGROUND/AIMS: The relationship between Crohn's disease and gallstones is established. However, the prevalence and risk factors for gallstones in patients with ulcerative colitis (UC) are not yet well understood. The aim of this study was to evaluate the prevalence and risk factors of gallstones in patients with UC. METHODS: This study was a retrospective single center study. A total of 87 patients with UC and 261 healthy controls were enrolled. Age, sex, and body mass index were matched. To investigate risk factors, the extent of UC, duration of disease, number of hospital admissions, and number of steroid treatments in patients with UC were evaluated. RESULTS: The prevalence of gallstones in patients with UC was 13.8%, whereas that in healthy controls was only 3.1% (P<0.001). For patients with UC, patients > or =50 years of age had a 3.6-times higher risk of gallstones compared to that in those <50 years of age, and the difference was statistically significant (odds ratio, 3.60; confidence interval, 1.03-12.61) in univariate analysis. There were no statistically significant disease-related risk factors for gallstones in UC patients. CONCLUSIONS: This is the first study of gallstone prevalence in Korean UC patients. In this study, patients with UC had a higher prevalence of gallstones compared to that in well-matched healthy controls. Age seemed to be a possible risk factor, and more studies are needed. Further prospective, large-scale studies will be required to confirm the risk factors for gallstones in UC patients.
Asymptomatic Diseases ; Body Mass Index ; Colitis, Ulcerative* ; Crohn Disease ; Gallstones* ; Humans ; Prevalence ; Retrospective Studies ; Risk Factors

Spontaneous arterial bleeding has been reported rarely. In a patient consuming heavy amounts of alcohol with alcoholic liver cirrhosis, spontaneous bleeding can be evoked by thrombocytopenia, altered platelet function, and shear stress on fully dilated arteries by portal hypertension. Alcohol consumption itself can also predispose a patient to bleeding by influencing the aggregation and activation of platelets, and altering the coagulation and fibrinolysis pathway. All of these mechanisms could cause patients with alcoholic liver cirrhosis to bleed spontaneously; however, conditions inducing peripheral arterial bleeding are very rare. Here, we report three cases of spontaneous arterial bleeding in patients with liver cirrhosis consuming heavy amounts of alcohol. All of the patients bled without any physical trauma, and the involved arteries were the intercostal arteries in two cases and a gastroduodenal artery in the other case. The patients were treated by angiographic embolization. One expired due to recurrence of arterial bleeding despite repeated angiographic embolization and massive transfusion.
Alcohol Drinking ; Arteries ; Blood Platelets ; Embolization, Therapeutic ; Fibrinolysis ; Hemorrhage* ; Humans ; Hypertension, Portal ; Liver Cirrhosis ; Liver Cirrhosis, Alcoholic* ; Recurrence ; Thrombocytopenia

Amyloidosis is a group of disorders characterized by the extracellular accumulation of insoluble, fibrillar proteins in various organs and tissues. It is classified, on the basis of the identity of the precursor protein, as primary, secondary, or familial amyloidosis. Gastrointestinal amyloidosis usually presents as bleeding, ulceration, malabsorption, protein loss, and diarrhea. However, gastric amyloidosis with gastric outlet obstruction mimicking linitis plastica is rare. We report a case of gastrointestinal amyloidosis with gastric outlet obstruction in a patient with ankylosing spondylitis. The patient was indicated for subtotal gastrectomy because of the aggravation of obstructive symptoms, but refused the operation and was transferred to another hospital. Three months later, the patient died of aspiration pneumonia during medical treatment.
Amyloidosis* ; Amyloidosis, Familial ; Diarrhea ; Gastrectomy ; Gastric Outlet Obstruction* ; Hemorrhage ; Humans ; Linitis Plastica ; Pneumonia, Aspiration ; Spondylitis, Ankylosing* ; Ulcer

Foreign bodies in the upper esophagus should be removed as soon as possible to avoid serious complications. These foreign bodies can penetrate the bowel wall and cause severe complications. The peristalsis of the esophagus is not strong enough to prevent it from retaining swallowed objects. Hence, perforation from a foreign body is more likely to occur in the esophagus than in the rest of the gastrointestinal tract. A razor blade is a rare foreign body of the esophagus. Its sharpness and large size make it difficult to remove. A razor blade was very firmly impacted in the esophageal wall in our case, and the razor blade had not moved from the upper esophagus. A standard overtube has limitations to remove a razor blade inside the overtube's lumen. We report here on a case of using a wedge resected overtube made it possible to successfully extract a razor blade and no serious complications occurred after extraction of the razor blade.
Esophagus ; Foreign Bodies ; Gastrointestinal Tract ; Peristalsis

Ischemic colitis is generally considered a disease of the elderly. The causes of ischemic colitis include low-flow states due to cardiac dysfunction or hypovolemia and certain medications including estrogen. Here we report a case of ischemic colitis in a 26-year-old woman. She had no specific medical history except taking oral-contraceptives for a long time. The mechanism of estrogen-induced ischemic colitis is not clearly understood. But we recommend that oral-contraceptives should be considered as a cause of ischemic colitis in young women.
Adult ; Aged ; Colitis, Ischemic ; Contraceptives, Oral ; Estrogens ; Female ; Humans ; Hypovolemia