TLR5 signaling attenuates acetaminophen-induced acute liver injury by inducing regulatory T cells in mice

Zixiong Zhou(강사),Jong-Won Kim,Jing Qi,Chae Woong Lim,Bumseok Kim 한국실험동물학회 2019 한국실험동물학회 학술발표대회 논문집 Vol.2019 No.7

Treatment of cigarette smoke extract and condensate differentially potentiates palmitic acid-induced lipotoxicity and steatohepatitis <i>in vitro</i>

Zhou, Zixiong,Kim, Jong Won,Zhao, Jing,Qi, Jing,Choi, Seong Jin,Lim, Chae Woong,Lee, Moo-Yeol,Lee, Kyuhong,Kim, Bumseok Elsevier 2018 Toxicology in vitro Vol.52 No.-

<P><B>Abstract</B></P> <P>Accumulative evidence showed that cigarette smoke (CS) detrimentally affects the pathogenesis of nonalcoholic steatohepatitis (NASH). The purpose of this study was to evaluate the effects of CS extract (CSE) or total particulate matter (TPM) on the <I>in vitro</I> steatohepatitis model using mouse primary hepatocytes treated with palmitic acid (PA) or PA plus LPS. Increased hepatocellular damage was observed in PA-treated hepatocytes with TPM or CSE treatment, but increased triglyceride level was only observed in PA plus LPS-treated hepatocytes with a high concentration of TPM. Also, expression levels of steatohepatitis-related genes such as TNF-α, NOS 2, and SREBP-1c were significantly increased after treatment of TPM. To further demonstrate the role of Kupffer cells (KCs) after CS extracts treatment, trans-well co-culture system of hepatocytes and KCs was utilized. The levels of inflammatory cytokines and the ratios of Bax/Bcl-2 (apoptosis-related genes) were markedly increased in co-cultured hepatocytes after TPM or CSE treatment. Interestingly, KCs activation was augmented in KCs upon treatment with CSE or TPM. Overall, our findings indicate that <I>in vitro</I> treatment with CSE or TPM differentially contributes to the severity of steatohepatitis by modulating steatohepatitis-related lipotoxicity and inflammation, which might be caused by KCs activation with subsequent induction of hepatocytes apoptosis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> 0.4 mM PA treatment could induce steatohepatitis on primary hepatocytes. </LI> <LI> Increased hepatotoxicity was observed in PA-treated hepatocyte after CS treatment. </LI> <LI> CS treatment enhanced PA-induced inflammation and oxidative stress levels. </LI> <LI> TPM treatment increased PA plus LPS-induced lipotoxicity. </LI> <LI> CS enhanced PA-induced apoptosis of hepatocytes when co-cultured with KCs. </LI> </UL> </P>

Evaluation of different media for ex vivo porcine lung culture model

Yang, Myeon-Sik,Zhou, Zixiong,Khatun, Amina,Nazki, Salik,Jeong, Chang Gi,Kim, Won Il,Lee, Sang Myeong,Kang, Seog-Jin,Lim, Chae Woong,Kim, Bumseok The Korean Society of Veterinary Service 2018 韓國家畜衛生學會誌 Vol.41 No.4

Developing drugs targeting respiratory pathogen is essential to control respiratory diseases. Many experiments have been performed under in vivo situation. However, in vivo experiments have economical and ethical issues. The objective of this study was to determine the possibility of developing an ex vivo lung culture system with possible application for respiratory infection studies. After isolating lungs from naïve pigs, agarose-inflated lung tissues were prepared and sliced manually. These sliced lung tissues were then subsequently placed on 24-well plates. Eight different combinations of media were used to determine the optimum ex vivo lung culture condition. In addition, lung tissues were infected with porcine reproductive and respiratory syndrome (PRRS) virus at a titer of $1{\times}10^4\;TCID_{50}/mL$. Virus growth was confirmed by titration in MARC-145 cells at 2, 4, 6 days post infection (dpi). We found that ex vivo lung culture in physiological environment was not media specific based on histopathology and cytotoxicity. However, under virus-infected condition, thickened alveolar walls in the lung tissues and stable virus titers at 2, 4, 6 dpi were shown in F12K medium suggesting that it was useful for tissue maintenance and virus infection using PRRS virus infected lung tissues. The present study shows the possibility of using porcine ex vivo lung model for respiratory infection studies.

Evaluation of different media for ex vivo porcine lung culture model

Myeon-Sik Yang,Zixiong Zhou,Amina Khatun,Salik Nazki,정창기,김원일,이상명,Seog-Jin Kang,임채웅,김범석 한국동물위생학회 2018 韓國家畜衛生學會誌 Vol.41 No.4

Developing drugs targeting respiratory pathogen is essential to control respiratory diseases. Many experi-ments have been performed under in vivo situation. However, in vivo experiments have economical and ethical issues. The objective of this study was to determine the possibility of developing an ex vivo lung culture system with possible application for respiratory infection studies. After isolating lungs from naïve pigs, agarose-inflated lung tissues were prepared and sliced manually. These sliced lung tissues were then subsequently placed on 24-well plates. Eight different combinations of media were used to determine the optimum ex vivo lung culture condition. In addition, lung tissues were infected with por-cine reproductive and respiratory syndrome (PRRS) virus at a titer of 1×104 TCID50/mL. Virus growth was confirmed by titration in MARC-145 cells at 2, 4, 6 days post infection (dpi). We found that ex vivo lung culture in physiological environment was not media specific based on histopathology and cytotoxicity. However, under virus-infected condition, thickened alveolar walls in the lung tissues and stable virus titers at 2, 4, 6 dpi were shown in F12K medium suggesting that it was useful for tissue maintenance and virus infection using PRRS virus infected lung tissues. The present study shows the possibility of using porcine ex vivo lung model for respiratory infection studies.

Γ-Aminobutyric acid promotes methionine-choline deficient diet-induced nonalcoholic steatohepatitis

Seok Roh, Yoon,Cho, Ara,Zhou, Zixiong,Jeong, Hyuneui,Park, Jeong-Eun,Cha, Youn-Soo,Oh, Suk-Heung,Lim, Chae-Woong,Kim, Bumseok Editorial Department of Journal of Biomedical Rese 2017 JOURNAL OF BIOMEDICAL RESEARCH -ELSEVIER- ENGLISH Vol.31 No.1

<P><B>Abstract</B></P><P>Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases and a major cause of liver fibrosis worldwide. Γ-Aminobutyric acid (GABA) is one of the most abundant inhibitory neurotransmitters in the central nervous system. Recently, it has been reported that GABAergic signaling pathways are found in various non-neuronal tissues including the immune system and play a functional role. In the present study, we investigated whether administration of GABA has effects on NASH through its immunomodulatory effects. To test this hypothesis, C57BL/6 mice were fed a methionine–choline-deficient (MCD) diet for 8 weeks. After four weeks into MCD feeding, mice were provided with plain water (control) or water containing 2 mg/mL of GABA for the subsequent 4 weeks. Using this MCD diet-induced NASH model, we found that mice receiving GABA showed more severe steatohepatitis and liver fibrosis than control mice. This increased liver damage was confirmed by higher levels of serum alanine transaminase (ALT) and aspartate aminotransferase (AST) compared to the control group. In accordance with increased liver steatohepatitis, NASH-related and inflammatory gene expression (collagen α1, tissue inhibitor of metalloproteinase-1, TNF-α) in the liver was markedly increased in GABA-treated mice. Furthermore, GABA directly enhanced production of inflammatory cytokines including IL-6 and TNF-α in LPS activated RAW macrophage cells and increased TIB–73 hepatocyte death. Such effects were abolished when GABA was treated with bicuculline, a competitive antagonist of GABA receptors. These results suggest that oral administration of GABA may be involved in changes of the liver immune milieu and conferred detrimental effects on NASH progression.</P>

Structure effect of a suction pipe on slag-discharging performance in a shaft boring machine

Hejia Jiang,Laikuang Lin,Zhongbao Wen,Xuemeng Xiao,Zixiong Zhou,Yimin Xia 대한기계학회 2023 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.37 No.9

The efficiency and stability of shaft boring machines depend critically on the slag-discharging system. In this study, we simulate the slagging process by using the coupled computational fluid dynamics/discrete element method and validate the method’s reliability through experiments. We investigate the impact of outlet diameter, inlet diameter, and outlet section length on slag-discharging performance. We establish the slag-discharging principle of the suction pipe by analyzing the particle motion trajectory. The flow field close to the suction pipe can be classified into collecting and lifting zones on the basis of the main flow direction velocity. Furthermore, we propose pipes with seven typical types, among which the straightconical type exhibits the most favorable slag-discharging performance. The straight-conical pipe enhances the slag-discharging mass by 22.49 % compared with the straight pipe.

Design and dimension optimization of cutter disassembly mechanism for shield tunneling machine

Yi-Min Xia,Mei Yang,Zhiyong Ji,Lianhui Jia,Zixiong Zhou,Dun Wu 대한기계학회 2021 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.35 No.7

This study focuses on configuration and dimension optimization of cutter disassembly mechanism. Firstly, a cutter disassembly mechanism configuration is proposed with four components and simple actions, based on the theory of inventive problem solving (TRIZ) contradiction solutions. Furthermore, a comprehensive dimension optimization strategy was developed, including non-dimensional normalization model, kinematic performance atlases and fuzzy comprehensive evaluation method. Then, the optimal relative dimension of crucial parameters was obtained. Combined with the assembly relationship between components, dimension of all parameters was designed for cutter disassembly mechanism. The locking and disassembling process simulation was provided to illustrate the feasibility of the mechanism. The results show that the angular velocity is very smooth and the locking and disassembling actions are realizable without interference for optimized cutter disassembly mechanism. The effectiveness of the configuration and dimension optimization method is validated.