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.

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.

Feasibility of Lignin-Carbohydrate Complexes Based Spherical Bio-carries in Hepatocytes Cultivation

Yi-Min Xie,Hou-Kuan Zhao,Zhe-Zi Ye,Peng Wang,Jin-Ling Li,Shao-Qiong Zeng 한국펄프·종이공학회 2016 한국펄프·종이공학회 학술발표논문집 Vol.2016 No.10

Analysis of particle motion and wear characteristics for mixed particle sizes in centrifugal pumps

Yi Li,Haiyang Zhang,Zhe Lin,Guang Zhang,ZuChao Zhu 대한기계학회 2023 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.37 No.9

In this study, we investigated the effect of particle size distribution (PSD) variations on the particle motion characteristics and wear in centrifugal pumps. We used computational fluid dynamics (CFD) and the discrete element method (DEM) to conduct simulations for one single particle size and five mixed particle sizes. The variation of the PSD had a significant effect on the wear rate of the impeller pressure surface and the volute surface. When the proportion of small particles near the impeller increased, the wear rate decreased. Specifically, at the middle of the impeller, the wear rate changed the most significantly. For volute surfaces 6-7 and 7-8 and the diffusion section, the velocity vectors of the near-wall volute surface showed a greater accumulation of small particles, and the buffering effect on the impact of large particles increased. Thus, the addition of small particles caused the wear rate of the volute surface to decrease.

한국인 및 중국 한족 정신분열병 환자의 5-HT2A 수용체 유전자 -1438A/G 다형성

이장호,이광철,이승부,오용인,최영근,조아랑,정주호,장환일 大韓神經精神醫學會 2005 신경정신의학 Vol.44 No.1

Objectives : The purpose of the present study was to investigate the association between -1438A/G polymorphism of 5-HT2A receptor gene and schizophrenia in Korean and Han Chinese population. Methods : A sample of 184 Korean patients with schizophrenia and 96 Korean healthy normal controls and 96 Han Chinese patients with schizophrenia and 96 Han-Chinese healthy normal controls were genotyped for a single nucleotide polymorphism with in 5-HT2A receptor gene (promoter region, A-1438G) by Msp I Resthction Fragment Length Polymorphism (RFLP). Results : There was no difference in allelic frequencies and genotype frequencies of -1438A/G polymorphism between Korean schizophrenics and controls (p=0.13) and Han Chinese schizophrenics and controls (p=0.40). Also, -1438A/G Poly-morphism did not show ethnical difference between Korean and Han Chinese controls. The Scale for the Assessment of Negative Symptoms (SANS) scores showed no significant differences between genotypes of -1438A/G polymorphism in both of Korean and Han Chinese schizophrenics. Conclusion : These results suggest that -1438A/G polymorphism of the 5-HT2A receptor gene is not causally related to the development of schizophrenia in Korean and Han Chinese population, and there no ethnic difference between Korean and Han Chinese population.

Process Design and Longitudinal Deformation Prediction in Continuous Sheet Metal Roll Forming for Three- Dimensional Surface

Zhong-Yi Cai,Lin-Lin Li,Mi Wang,Ming-Zhe Li 한국정밀공학회 2014 International Journal of Precision Engineering and Vol. No.

Continuous roll forming (CRF) is a process to form three-dimensional surface based on the rolling deformation of sheet metal. Unliketraditional rolling process where the working rolls are straight and rigid, two small-diameter bendable forming rolls are used herein,and the sheet metal is bent in longitudinal and transverse directions simultaneously after it is compressed between a pair of bendedrolls. The formed surface is controlled by the curved shapes of the forming rolls and the gap between the two rolls, and the roll gapis the crucial parameter of CRF process. In this paper, the required velocity distribution of material across the exit of roll gap forthe formation of a smooth surface is analyzed, the formulations for the CRF process design is derived and a method to predict thelongitudinal bending deformation generated by roll gap is presented. Finally, the validity of the presented methods and theoreticalmodels are demonstrated by numerical simulations and CRF tests for typical surface parts.

Continuous Sheet Metal Forming for Doubly Curved Surface Parts

Zhong-Yi Cai,Ying-Wu Lan,Ming-Zhe Li,Zhi-Qing Hu,Mi Wang 한국정밀공학회 2012 International Journal of Precision Engineering and Vol. No.

Continuous sheet metal forming (CSMF) is a novel technology for manufacturing doubly curved sheet metal parts. In this process,an upper flexible roll and two lower flexible rolls are employed as a forming tool, with the rotation of flexible rolls, the sheet metal is bent in the longitudinal and transverse directions simultaneously. In this study, the basic principle of CSMF system is introduced and the basic mathematical model to control the CSMF process is presented. Based on the analysis of the sheet metal deformation in longitudinal direction, the formulations to determine the finial curvature of the deformed sheet metal and to estimate the downward displacement of upper roll are obtained. Forming experiments for torus-shaped surface and saddle-shaped surface were carried out. The dimensional accuracy and smoothness of the CSMF parts were measured and analyzed. The experiment results confirm the validity of the presented mathematical models and shows that CSMF can be effectively used in forming of doubly curved surface parts.

Fast Hardware Implementations of Inversions in Small Finite Fields for Special Irreducible Polynomials on FPGAs

Haibo Yi,Weijian Li,Zhe Nie 보안공학연구지원센터 2016 International Journal of Security and Its Applicat Vol.10 No.9

Inversions in small finite fields are the most computationally intensive field arithmetic and have been playing a key role in areas of cryptography and engineering. The main algorithms for small finite field inversions are based on Fermat's little theorem, extended Euclidean algorithm, Itoh-Tsujii algorithm and other methods. In this brief, we present techniques to exploit special irreducible polynomials for fast inversions in small finite fields GF(2n) , where n is a positive integer and 0 < n < 16 . Then, we propose fast inversions based on Fermat's theorem for two special irreducible polynomials in small finite fields, i.e. trinomials and All-One-Polynomials (AOPs). Trinomials can be represented by polynomials xn + xm + 1 and AOPs can be represented by polynomials xn + Xn-1 + ... +1 , where m is a positive integer and 0 < m < n . Our designs have low hardware requirements, regular structures and are therefore suitable for hardware implementation. After that, our designs are programmed in Very-High-Speed Integrated Circuit Hardware Description Language (VHDL) by using integrated environment Altera Quartus II and implemented on a low-cost Field- Programmable Gate Array (FPGA). The experimental results on FPGAs show that our designs provide significant reductions in executing time of inversions in small finite fields, e.g. the executing time of inversion in GF(27) is 18.80 ns and the executing time of inversion in GF(212) is 29.57 ns.

Age and Sex Distribution of Chinese Chronic Cough Patients and Their Relationship With Capsaicin Cough Sensitivity

Kefang Lai,Li Long,Fang Yi,Jiaman Tang,Zhe Chen,Fagui Chen,Jianmeng Zhou,Wen Peng,Liting Zhang,Hu Li,Wenzhi Zhan,Ruchong Chen,Wei Luo,Qiaoli Chen,Kian Fan Chung,Nanshan Zhong 대한천식알레르기학회 2019 Allergy, Asthma & Immunology Research Vol.11 No.6

Purpose: An older female predominance has been reported among chronic cough patients in Western countries, which is considered to be associated with a higher cough sensitivity in females. However, the characteristics of Chinese chronic cough patients remain unclear. This study aimed to explore the age and sex distribution as well as their relationship with cough reflex sensitivity to capsaicin in Chinese chronic cough patients. Methods: We analyzed the demographic features of 1,882 consecutive chronic cough patients who attended our cough clinic in Guangzhou, China. Cough sensitivity to capsaicin, which was defined as the lowest concentration of capsaicin causing 5 coughs or more (C5), was measured in 539 of the 1,882 patients and 68 healthy volunteers. Results: The mean age of the patients was 43.0 ± 13.7 years and patients aged <50 years accounted for more than two-thirds of the study population. Around 87% of the patients were never-smokers. The proportion of females (51.5%) was almost equal to that of males (48.5%). The pattern of the age and sex distribution was consistently reflected within most common causes of chronic cough, while a female predominance was shown in patients with coughvariant asthma and patients aged ≥50 years. Female patients had higher cough sensitivity to capsaicin than male patients (log C5: 1.58 ± 0.84 vs. 2.04 ± 0.84 μmol/L, P = 0.001), and patients aged ≥50 years had higher cough sensitivity to capsaicin than patients aged <50 years. Conclusions: In China, patients with chronic cough have a roughly equal sex distribution and a middle-aged predominance, irrespective of a higher cough sensitivity to capsaicin in females and older patients.

Lipid Emulsion as a Drug Delivery System for Breviscapine: Formulation Development and Pptimization

( Jun Wei Li ),( Li Gao ),( Yi Dong Yan ),( Roshan Pradhan ),( Jong Oh Kim ),( Qi Zhe Quan ) 영남대학교 약품개발연구소 2012 영남대학교 약품개발연구소 연구업적집 Vol.22 No.0

In this study, we developed an optimized formulation of a breviscapine lipid emulsion (BLE) and evaluated the physicochemical properties and in vivo pharmacokinetics of BLE in rats. For the preparation of the lipid emulsion, soybean oil and oleic acid were used as the oil phase, lecithin and poloxamer 188 as surfactants and glycerol as co-surfactant. An optimized formulation consisting of soybean oil (10.0%), oleic acid (0.9%), lecithin (1.5%), poloxamer 188 (0.4%), and glycerol (2.25%) was selected. The results showed that the average particle size, polydispersity index, and zeta potential of the optimized formulation were 183.5 ± 5.5 nm, 0.098 ± 0.046, and -35.0 ± 2.5 mV, respectively. The BLE was stable for at least three month at room temperature. After a single intravenous dose of 4 mg/kg to rats, the AUC of scutellarin from the lipid emulsion was about 1.5-fold higher than that of the commercial product (breviscapine injection). In conclusion, the optimizedformulation of BLE showed positive results over the commercial product in terms of the physicochemical properties and pharmacokinetics of BLE in rats.