Potassium Acetate Blocks Clostridium difficile Toxin A-Induced Microtubule Disassembly by Directly Inhibiting Histone Deacetylase 6, Thereby Ameliorating Inflammatory Responses in the Gut

( Li Fang Lu ),( Dae Hong Kim ),( Ik Hwan Lee ),( Ji Hong ),( Peng Zhang ),( I Na Yoon ),( Jae Sam Hwang ),( Ho Kim ) 한국미생물 · 생명공학회 2016 Journal of microbiology and biotechnology Vol.26 No.4

Clostridium difficile toxin A is known to cause deacetylation of tubulin proteins, which blocks microtubule formation and triggers barrier dysfunction in the gut. Based on our previous finding that the Clostridium difficile toxin A-dependent activation of histone deacetylase 6 (HDAC-6) is responsible for tubulin deacetylation and subsequent microtubule disassembly, we herein examined the possible effect of potassium acetate (PA; whose acetyl group prevents the binding of tubulin to HDAC-6) as a competitive/false substrate. Our results revealed that PA inhibited toxin A-induced deacetylation of tubulin and recovered toxin A-induced microtubule disassembly. In addition, PA treatment significantly decreased the production of IL-6 (a marker of inflamed tissue) in the toxin A-induced mouse enteritis model. An in vitro HDAC assay revealed that PA directly inhibited HDAC-6-mediated tubulin deacetylation, indicating that PA acted as a false substrate for HDAC-6. These results collectively indicate that PA treatment inhibits HDAC-6, thereby reducing the cytotoxicity and inflammatory responses caused by C. difficile toxin A.

Oxymatrine Causes Hepatotoxicity by Promoting the Phosphorylation of JNK and Induction of Endoplasmic Reticulum Stress Mediated by ROS in LO2 Cells

Li-li Gu,Zhe-lun Shen,Yang-Lei Li,Yi-Qi Bao,Hong Lu 한국분자세포생물학회 2018 Molecules and cells Vol.41 No.5

Oxymatrine (OMT) often used in treatment for chronic hepatitis B virus infection in clinic. However, OMT–induced liver injury has been reported. In this study, we aim to investigate the possible mechanism of OMT-induced hepatotoxicity in human normal liver cells (L02). Exposed cells to OMT, the cell viability was decreased and apoptosis rate increased, the intracellular markers of oxidative stress were changed. Simultaneously, OMT altered apoptotic related proteins levels, including Bcl-2, Bax and pro-caspase-8/-9/-3. In addition, OMT enhanced the protein levels of endoplasmic reticulum (ER) stress makers (GRP78/Bip, CHOP, and cleaved-Caspase-4) and phosphorylation of c-Jun N-terminal kinase (p-JNK), as well as the mRNA levels of GRP78/Bip, CHOP, caspase-4, and ER stress sensors (IREI, ATF6, and PERK). Pre-treatment with Z-VAD-fmk, JNK inhibitor SP600125 and N-acetyl-l-cysteine (NAC), a ROS scavenger, partly improved the survival rates and restored OMT-induced cellular damage, and reduced caspase-3 cleavage. SP600125 or NAC reduced OMT-induced p-JNK and NAC significantly lowered caspase-4. Furthermore, 4-PBA, the ER stress inhibitor, weakened inhibitory effect of OMT on cells, on the contrary, TM worsen. 4-PBA also reduced the levels of p-JNK and cleaved-caspase-3 proteins. Therefore, OMT-induced injury in L02 cells was related to ROS mediated p-JNK and ER stress induction. Antioxidant, by inhibition of p-JNK or ER stress, may be a feasible method to alleviate OMT-induced liver injury.

A new high-order response surface method for structural reliability analysis

Li, Hong-Shuang,Lu, Zhen-Zhou,Qiao, Hong-Wei Techno-Press 2010 Structural Engineering and Mechanics, An Int'l Jou Vol.34 No.6

In order to consider high-order effects on the actual limit state function, a new response surface method is proposed for structural reliability analysis by the use of high-order approximation concept in this study. Hermite polynomials are used to determine the highest orders of input random variables, and the sampling points for the determination of highest orders are located on Gaussian points of Gauss-Hermite integration. The cross terms between two random variables, only in case that their corresponding percent contributions to the total variation of limit state function are significant, will be added to the response surface function to improve the approximation accuracy. As a result, significant reduction in computational cost is achieved with this strategy. Due to the addition of cross terms, the additional sampling points, laid on two-dimensional Gaussian points off axis on the plane of two significant variables, are required to determine the coefficients of the approximated limit state function. All available sampling points are employed to construct the final response surface function. Then, Monte Carlo Simulation is carried out on the final approximation response surface function to estimate the failure probability. Due to the use of high order polynomial, the proposed method is more accurate than the traditional second-order or linear response surface method. It also provides much more efficient solutions than the available high-order response surface method with less loss in accuracy. The efficiency and the accuracy of the proposed method compared with those of various response surface methods available are illustrated by five numerical examples.

Seismic fragility assessment of self-centering RC frame structures considering maximum and residual deformations

Lu-Xi Li,Hong-Nan Li,Chao Li 국제구조공학회 2018 Structural Engineering and Mechanics, An Int'l Jou Vol.68 No.6

Residual deformation is a crucial index that should be paid special attention in the performance-based seismic analyses of reinforced concrete (RC) structures. Owing to their superior re-centering capacity under earthquake excitations, the post-tensioned self-centering (PTSC) RC frames have been proposed and developed for engineering application during the past few decades. This paper presents a comprehensive assessment on the seismic fragility of a PTSC frame by simultaneously considering maximum and residual deformations. Bivariate limit states are defined according to the pushover analyses for maximum deformations and empirical judgments for residual deformations. Incremental Dynamic Analyses (IDA) are conducted to derive the probability of exceeding predefined limit states at specific ground motion intensities. Seismic performance of the PTSC frame is compared with that of a conventional monolithic RC frame. The results show that, taking a synthetical consideration of maximum and residual deformations, the PTSC frame surpasses the monolithic frame in resisting most damage states, but is more vulnerable to ground motions with large intensities.

A new high-order response surface method for structural reliability analysis

Hong-Shuang Li,Zhen-Zhou Lu,Hong-Wei Qiao 국제구조공학회 2010 Structural Engineering and Mechanics, An Int'l Jou Vol.34 No.6

In order to consider high-order effects on the actual limit state function, a new response surface method is proposed for structural reliability analysis by the use of high-order approximation concept in this study. Hermite polynomials are used to determine the highest orders of input random variables, and the sampling points for the determination of highest orders are located on Gaussian points of Gauss-Hermite integration. The cross terms between two random variables, only in case that their corresponding percent contributions to the total variation of limit state function are significant, will be added to the response surface function to improve the approximation accuracy. As a result, significant reduction in computational cost is achieved with this strategy. Due to the addition of cross terms, the additional sampling points, laid on two-dimensional Gaussian points off axis on the plane of two significant variables, are required to determine the coefficients of the approximated limit state function. All available sampling points are employed to construct the final response surface function. Then, Monte Carlo Simulation is carried out on the final approximation response surface function to estimate the failure probability. Due to the use of high order polynomial, the proposed method is more accurate than the traditional second-order or linear response surface method. It also provides much more efficient solutions than the available high-order response surface method with less loss in accuracy. The efficiency and the accuracy of the proposed method compared with those of various response surface methods available are illustrated by five numerical examples.

A preparation and performance study of glass-ceramic glazes derived from blast furnace slag and fly ash

Hong-xia Lu,Man He,Yuan-yuan Liu,Jing-fei Guo,Li-wei Zhang,Deliang Chen,Hai-long Wang,Hong-liang Xu,Rui Zhang 한양대학교 세라믹연구소 2011 Journal of Ceramic Processing Research Vol.12 No.5

Glass-ceramic glazes have been prepared successfully via crystallization from blast-furnace slag (BFS), fly ash (FA) fluxed with potash feldspar and borax. The crystalline behavior of glass-ceramic glazes was investigated using differential thermal analysis and thermogravimetric analysis (DTA/TG), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Results revealed that the major crystalline phases are anorthite (CaAl2Si2O8) and akermanite (Ca2MgSi2O7) and crystalline phases disperse well in glassy phases with a uniform size of 1 μm. Glass-ceramic glazes possess low density, low water absorption,perfect stain resistance, acid resistance and alkali resistance. The thermal expansion coefficient of glass-ceramic glazes is steady up to 800 oC with an average value of 7.2 × 10−6 /K. Final results suggest that BFS and FA have potential to be vitrified into economically and environmentally low-cost glass-ceramic glaze materials.

Preparation and Characterization of Anti-GP73 Monoclonal Antibodies and Development of Double-antibody Sandwich ELISA

Li, Qi-Wen,Chen, Hong-Bing,Li, Zhi-Yang,Shen, Peng,Qu, Li-Li,Gong, Lai-Ling,Xu, Hong-Pan,Pang, Lu,Si, Jin Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.5

Background: Serum Golgi protein 73 (GP73) as a novel and potential marker for diagnosing hepatocellular carcinoma (HCC) have been found to be elevated in HCC patients and associated with clinical variables representing tumor growth and invasiveness. The aim of this study was to prepare a pair of monoclonal antibodys (mAbs) against GP73 and develop a newly designed double-antibody sandwich enzyme-linked immunosorbent assay (s-ELISA), which would be used in the detection of serum GP73 (sGP73) as well as in the diagnosis of HCC. Materials and Methods: Produced by prokaryotic expression, the purified recombinant GP73 (rGP73), produced by prokaryotic expression, was used to immunize the Balb/c mice. Two hybridoma cell lines against GP73 were obtained by fusing mouse Sp2/0 myeloma cells with spleen cells from the immunized mice. The titers of anti-GP73 mAb reached 1:243,000. Western blotting analysis and Immunohistochemistry staining revealed that anti-GP73 mAb could recognize GP73 protein. The double-antibody s-ELISA was successfully established and validated by 119 HCC and 103 normal serum samples. Results: showed that the detection limit of this method could reach 1.56 ng/ml, and sGP73 levels in HCC group (mean=190.6 ng/ml) were much higher than those of in healthy controls (mean=70.92 ng/ml). Conclusions: Results of our study not only showed that sGP73 levels of HCC patients were significantly higher than those of healthy controls, but also indicated that the laboratory homemade anti-GP73 mAbs could be the optimal tool used in evaluating sGP73 levels, which would provide a solid foundation for subsequent clinical applications.

Risk Assessment of Secondary Primary Malignancies in Nasopharyngeal Carcinoma: A Big-Data Intelligence Platform-Based Analysis of 6,377 Long-term Survivors from an Endemic Area Treated with Intensity-Modulated Radiation Therapy during 2003-2013

Lu-Lu Zhang,Guo-Hong Li,Yi-Yang Li,Zhen-Yu Qi,Ai-Hua Lin,Ying Sun 대한암학회 2019 Cancer Research and Treatment Vol.51 No.3

Purpose The incidence, risk factors and survival impact of secondary primary malignancies (SPMs) among survivors of nasopharyngeal carcinoma (NPC) treated with definitive intensity-modulated radiation therapy (IMRT) with or without chemotherapy are poorly characterized. Materials and Methods Consecutive patients (n=6,377) from the big-data intelligence platform at Sun Yat-sen University Cancer Center, China (in a high-incidence area) with newly diagnosed non-metastatic pathologically proven non-keratinizing undifferentiated NPC treated with IMRT±chemotherapy between January 2003 and June 2013 were retrospectively analyzed. Cumulative incidence of SPMs was calculated using the Kaplan-Meier method. Cox proportional hazards model was used to identify potential risk factors for SPMs and assess whether SPMs affect overall survival. Results Of the 6,377 patients, 189 (3.0%) suffered SPMs (median follow-up, 62 months). One-, 2-, 3-, 4-, and 5-cumulative risks of SPMs were 0.4%, 0.9%, 1.6%, 2.2%, and 2.6%, respectively. Latency from start of IMRT to SPMs diagnosis was 37 months (range, 6 to 102 months). In patients with SPMs, 14.3% suffered SPMs within 1 year post-IMRT: 1-3 years, 38.1%; 3-5 years, 33.9%; and > 5 years, 13.7%. Lung cancer was the most common SPM (50/6,377, 0.78%). Multivariate analysis demonstrated sex (male, 64% increase), age (! 50 years, 68% increase), and smoking history (41% increase) were significant risk factors for SPMs, and SPMs were associated with poorer overall survival. Conclusion This large cohort study confirms SPMs a dreadful complication for long-term survivors of NPC treated with IMRT. SPMs negatively impact overall survival in NPC. Close follow-up is recommended for older male survivors with a smoking history.

Proteomic and Immunological Identification of Diagnostic Antigens from Spirometra erinaceieuropaei Plerocercoid

Yan Lu,Jia-Hui Sun,Li-Li Lu,Jia-Xu Chen,Peng Song,Lin Ai,Yu-Chun Cai,Lan-Hua Li,Shao-Hong Chen 대한기생충학열대의학회 2021 The Korean Journal of Parasitology Vol.59 No.6

Oxymatrine Causes Hepatotoxicity by Promoting the Phosphorylation of JNK and Induction of Endoplasmic Reticulum Stress Mediated by ROS in LO2 Cells

Gu, Li-li,Shen, Zhe-lun,Li, Yang-Lei,Bao, Yi-Qi,Lu, Hong Korean Society for Molecular and Cellular Biology 2018 Molecules and cells Vol.41 No.5

Oxymatrine (OMT) often used in treatment for chronic hepatitis B virus infection in clinic. However, OMT-induced liver injury has been reported. In this study, we aim to investigate the possible mechanism of OMT-induced hepatotoxicity in human normal liver cells (L02). Exposed cells to OMT, the cell viability was decreased and apoptosis rate increased, the intracellular markers of oxidative stress were changed. Simultaneously, OMT altered apoptotic related proteins levels, including Bcl-2, Bax and pro-caspase-8/-9/-3. In addition, OMT enhanced the protein levels of endoplasmic reticulum (ER) stress makers (GRP78/Bip, CHOP, and cleaved-Caspase-4) and phosphorylation of c-Jun N-terminal kinase (p-JNK), as well as the mRNA levels of GRP78/Bip, CHOP, caspase-4, and ER stress sensors (IREI, ATF6, and PERK). Pre-treatment with Z-VAD-fmk, JNK inhibitor SP600125 and N-acetyl-l-cysteine (NAC), a ROS scavenger, partly improved the survival rates and restored OMT-induced cellular damage, and reduced caspase-3 cleavage. SP600125 or NAC reduced OMT-induced p-JNK and NAC significantly lowered caspase-4. Furthermore, 4-PBA, the ER stress inhibitor, weakened inhibitory effect of OMT on cells, on the contrary, TM worsen. 4-PBA also reduced the levels of p-JNK and cleaved-caspase-3 proteins. Therefore, OMT-induced injury in L02 cells was related to ROS mediated p-JNK and ER stress induction. Antioxidant, by inhibition of p-JNK or ER stress, may be a feasible method to alleviate OMT-induced liver injury.