Slide Session : OS-GAS-03 ; Gastroenterology : Xanthine Oxidase Promotes Hyperuricemia and Nonal-coholic Fatty Liver Disease in Patients and Mice

( Chengfu Xu ),( Xingyong Wan ),( Chaohui Yu ),( Lei Xu ),( Ming Yan ),( Honglei Weng ),( Min Miao ),( Yan Sun ),( Genyun Xu ),( Steven Dooley ),( William Coleman ),( Youming Li ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Hyperuricemia has been commonly found in patients with nonalcoholic fatty liver disease (NAFLD). This study aimed to clarify the causal relationship between NAFLD and hyperuricemia and to explore their underlying mechanisms. Methods: First, we evaluated the impact of NAFLD on development of hyperuricemia in a cohort of 5541 hyperuricemia-free individuals. Second, we analyzed the involvement of xanthine oxidase (XO), a rate-limiting enzyme catalyzes uric acid production, in the relationship between NAFLD and hyperuricemia in cultured HepG2 cells and a murine model of NAFLD. Results: In the first study, 7-year prospective analysis found that NAFLD was strongly associated with subsequent development of hyperuricemia. Cox proportional hazards regression analyses showed that the age, gender, and body mass index adjusted hazard ratio (95% CI) for incident hyperuricemia was 1.609 (1.129 - 2.294) in individuals with NAFLD compared with those without NAFLD. In the second study, we observed that the expression and activity of XO were significantly increased in cellular and mouse models of NAFLD. Knocking down XO expression or inhibiting XO activity significantly inhibited uric acid production and attenuated free fatty acids (FFA)-induced fat accumulation in HepG2 cells. Inhibition of XO activity also significantly decreased serum uric acid levels and ameliorated high fat diet-induced hepatic steatosis in mice. Further experiments indicated that XO regulates the activation of NLRP3 inflammasome, which may be essential for the regulatory effect of XO on NAFLD. Conclusions: XO promotes hyperuricemia and the development of NAFLD, which may serve as a novel therapeutic target for NAFLD.

A detector system for searching lost γ-ray source

Khan Waseem,He Chaohui,Cao Yu,Khan Rashid,Yang Weitao 한국원자력학회 2020 Nuclear Engineering and Technology Vol.52 No.7

The aim of this work is to develop a Geiger-Muller (GM) detector system for robot to look for a radioactive source in case of a nuclear emergency or in a high radiation environment. In order to find a radiation source easily, a detector system, including 3 detectors, was designed to search g-ray radiation sources autonomously. First, based on GEANT4 simulation, radiation dose rates in 3 Geiger-Muller (GM) counters were simulated at different source-detector distances, distances between detectors and angles. Various sensitivity analyses were performed experimentally to verify the simulated designed detector system. A mono-energetic 137Cs g-ray source with energy 662 keV and activity of 1.11 GBq was used for the observation. The simulated results were compared with the experimental dose rate values and good agreements were obtained for various cases. Only based on the dose rates in three detectors, the radiation source with a specific source activity and angle was localized in the different location. A method was adopted with the measured dose rates and differences of distances to find the actual location of the lost g-ray source. The corresponding angles of deviation and detection limits were calculated to determine the sensitivity and abilities of our designed detector system. The proposed system can be used to locate radiation sources in low and high radiation environments

Slide Session : OS-GAS-18 ; Gastroenterology : Bahd1: A Gatekeeper to Protect Us from Inflamma-tion-Associated Colon Disease?

( Huatuo Zhu ),( Xinyong Wan ),( Wenguo Chen ),( Chaohui Yu ),( Min Yue ),( Yining Dai ),( Lihua Chen ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: It was recently reported that epigenetics might play an essential role in IBD. Bromo adjacent homology domain 1 (BAHD1), which involved in category of epigenetics maintains homeostasis by promoting heterochromatin formation. Our study aimed to investigate the underlying mechanism of BAHD1 in gut inflammation including IBD, seeking a new therapeutic target for the inflammation-associated colon disease. Methods: Experimental colitis was induced in C57BL/6 mice by dextran sulfate sodium administration. To simulate the intestinal inflammation microenvironment for epithelial cells, Caco-2 cells were exposed to a mixture of LPS, TNF-a, IL-1ß, and IFN-. BAHD1 expression was detected by quantitative PCR(qPCR), western blot and immunohistochemistry in both UC patients and mice model. Small interfering RNA was used to knock down BAHD1 level(siBAHD1) in Caco-2 cells and associated cytokines(CKs) expression were detected by either qPCR or ELISA. Possible mechanism involving in- flammatory pathways activation were addressed by western blot. Results: Murine model of UC-like inflammation was successfully established. And we found that BAHD1 existed in the normal internal crypt and surface epithelial cells ubiquitously. Compared with control group, BAHD1 expression in colon tissue were significantly decreased in both UC patients and mice model. In the vitro model system, we found that the protein level of BAHD1 was decreased in the stimulated Caco-2 cells. In addition, consistent with mRNA level of associated CKs enhanced in the siBAHD1 group within stimulatory factors, the interference group secreted more IL-6 and MCP-1 contents in the culture supernatant. As for potential mechanisms of BAHD1 in colitis, increased expression of TNFR1 was found in Caco-2 cells pre-treated with siBAHD1 in gut inflammation model, accompanying with the activation of IKK/ NF-κB and JNK/AP-1 pathways. Conclusions: Collectively, those findings provide evidence that BAHD1 might act as an indispensable safeguard to keep intestine immunological homeostasis.

Slide Session : OS-GAS-02 ; Gastroenterology : Application of Machine Learning Techniques for Clin-ical Predictive Modeling: A Cross-Sectional Study on Nonalcoholic Fatty Liver Disease

( Han Ma ),( Chengfu Xu ),( Zhe Shen ),( Chaohui Yu ),( Youming Li ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Recent attention focuses on screening and prediction of NAFLD. Machine learning techniques are powerful and promising tools. Methods: A cross-sectional study was performed among 10,508 subjects who attended their annual health examination in the first affiliated hospital, College of Medicine, Zhejiang University, China in 2010. The questionnaires, Physical examinations, laboratory tests and liver ultrasonography were performed. 20 features (e.g., age, laboratory results) were extracted. Machine learning techniques were implemented on the open source software named Weka. The tasks included feature selection and classification. By removing redundant features, feature selection techniques built a screening model. Classification was used to build a prediction model, which was evaluated by F measure. Nine machine learning techniques were investigated, i.e., logistic regression, K-Nearest Neighbor, Support Vector Machine, naive Bayes, Bayesian network, decision tree, Adaboosting, bagging, and random forest. Results: A total of 2522(24%) subjects were fulfilled the diagnostic criteria of NAFLD. By using feature selection techniques, BMI, serum triglyceride, ALT, GGT and uric acid were the top-5 features contributing most to NAFLD. 10-fold cross-validation was used in classification to evaluate machine learning techniques, i.e., subjects were randomly divided into 10 folds, 9 folds were used to build a prediction model, the remaining fold was used to evaluate. The whole process lasted for 10 times, average performance was recorded. The results showed among the nine state-of-the-art machine learning techniques, Bayesian network demonstrated the best performance. It achieves the accuracy, specificity, sensitivity, and F-measure scores up to 83%, 0.787, 0.678, and 0.665, respectively. Compared with logistic regression, Bayesian network improves F-measure score by 10.83%. Conclusions: Novel machine learning techniques may have screening and predictive value for NAFLD.

The Role of Short Chain Fatty Acids in Irritable Bowel Syndrome

Wenxi Jian,Jiali Wu,Shefeng Zhu,Linying Xin,Chaohui Yu,Zhe Shen 대한소화기 기능성질환∙운동학회 2022 Journal of Neurogastroenterology and Motility (JNM Vol.28 No.4

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that is characterized by abdominal pain and disordered bowel habits. The etiology of IBS is multifactorial, including abnormal gut-brain interactions, visceral hypersensitivity, altered colon motility, and psychological factors. Recent studies have shown that the intestinal microbiota and its metabolites short chain fatty acids (SCFAs) may be involved in the pathogenesis of IBS. SCFAs play an important role in the pathophysiology of IBS. We discuss the underlying mechanisms of action of SCFAs in intestinal inflammation and immunity, intestinal barrier integrity, motility, and the microbiota-gut-brain axis. Limited to previous studies, further studies are required to investigate the mechanisms of action of SCFAs in IBS and provide more precise therapeutic strategies for IBS.

Slide Session : OS-GAS-05 ; Gastroenterology : 3-Mercaptopyruvate Sulfurtransferase Downregulation Ameliorates Hepatic Steatosis and Oxidative Stress Via Hydrogen Sulfi de Metabolism in Nonalcoholic Fatty Liver Disease

( Meng Li ),( Jiexia Ding ),( Xingyong Wan ),( Xi Jin ),( Shaohua Chen ),( Chaohui Yu ),( Youming Li ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: The mitochondrial enzyme 3-mercaptopyruvate sulfurtransferase (MPST) is a source of endogenous hydrogen sul.de (H2S), a gaseous signaling molecule implicated in a wide range of physiological processes. The mechanisms of pathogenesis underlying nonalcoholic fatty liver disease (NAFLD) remain unclear. The possible role of MPST in the development of NAFLD has never been investigated. Methods: The NAFLD cell model was established by treating L02 cells with free fatty acid (FFA) overload. A variety of cellular and molecular approaches were used to study the effects of MPST on hepatic steatosis, oxidative stress and inflammation involved in NAFLD. Results: After culturing L02 cells by FFA for 24h, we detected the increased protein level of MPST. MPST knockdown in L02 cells resulted in a marked decrease of lipid accumulation and downregulation of SREBP-1 pathway and melioration of oxdiative stress, embodied in decreased level of H2O2, MDA and IL-6, meanwhile, increased levels of ATP and MMP. Unexpectedly, we observed a significantly increased level of H2S after knockdown of MPST. And the expression of CSE was enhanced when the MPST was decreased. When the level of H2S was decreased, the TG and H2O2 content within FFA-induced hepatocytes were greatly raised. Meanwhile, we demonstrated the reversed expression of SREBP-1/ ACC pathway with the reduced level of H2S. Conclusions: We showed that MPST knockdown could stimulate the compensatory process of CSE, causing the increasing of H2S which is recently considered as a novel antioxidant gas. The increased endogenous H2S could improve hepatocyte steatosis and partly improve the process of oxidative stress and in. ammatory state of steatosis hepatocytes. MPST is implicated in NAFLD via its important H2S metabolism. It provided new insight into the pathogenic mechanisms of NAFLD, pointing to potential target for therapeutic strategy.