Magnesium isoglycyrrhizinate inhibits L-type Ca2+ channels, Ca2+ transients, and contractility but not hERG K+ channels

Yue Lin,Yuanyuan Zhang,Qiongtao Song,Tao Song,Xue Han,Ying Zhang,Xuan Zhang,Xi Chu,Fenghua Zhang,Li Chu,Jianping Zhang 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.10

To explore the cardiovascular protective effectsof Magnesium isoglycyrrhizinate (MI), especially theunderlying cellular mechanisms related to L-type calciumchannels and myocardial contractility, and to examine theeffects of MI on hERG K? current expressed in HEK293cells. We used the whole-cell patch clamp technique,video-based edge detection and dual excitation fluorescencephotomultiplier systems to explore the effect of MIon L-type Ca2? currents (ICa-L) and cell contraction in ratcardiomyocytes. We also examined the rapidly activatingdelayed rectifier potassium current (IKr) expressed inHEK293 cells using a perforated patch clamp. MI inhibitedICa-L in a dose-dependent manner, with a half-maximalinhibitory concentration (IC50) of 0.22 mg/ml, and themaximal inhibitory effect was 61.10 ± 0.59%. MI at aconcentration of 0.3 mg/ml reduced cell shortening by24.12 ± 3.97% and the peak value of the Ca2? transient by36.54 ± 4.96%. MI had no significant influence on hERGK? channels expressed in HEK293 cells at all testpotentials. MI exerts protective effects on the heart via theinhibition of ICa-L and cell shortening in rat cardiomyocytes. However, MI had no significant influence on IKr;thus, MI may exert cardioprotective effects without causingdrug-induced long QT syndrome.

An improved horizontally reversible plow design based on virtual assembly semantics and constraint

Lin Zhu,Shuang-Shuang Peng,Yin-Yin Qi,Xi Cheng,Wen-Feng Zhang,Liang-Yuan Xu,De-Quan Zhu 대한기계학회 2016 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.30 No.1

There exit model errors in the constructed Horizontally reversible plough (HRP) structure through Interference check technique (ICT). This is basically due to missing parts and geometric interference and, hence, has significantly adverse effects in improving HRP. In thispaper an improved design to refine the three dimensional (3D) model of HRP is implemented by using Virtual assembly technology(VAT). To achieve this, the authors propose a combined virtual assembly semantics and constraint for assembly planning and simulationof HRP in the commercial software, e.g., SolidWorks. First, the assembly planning of HRP was captured with a semantics-based model,including spatial position, assembly orientation, type and parameters of the semantic entities; secondly, the assembly simulation of HRPwas performed by using constraint-based VAT, e.g. component grasping, moving and releasing; finally, the obtained HRP model wasverified through ICT again. The results demonstrate that not any model error exists in the refined 3D HRP model any longer and thatsemantics and constrain based VAT can support the interactive operation more effectively and accurately than those with geometric constraints. This technique was previously used for HRP model. Based on the refined 3D HRP model, the design improvement of Remotecylinder base (RCB), an important component of HRP, will be forthcoming in a future paper.

Structural Stability and Electronic and Optical Properties of Coinage-Metal (4; 2) Alloy Nanotubes: A First-Principles Study

Xi-Zhi Wang,Liang-Cai Ma,Ling Ma,Xue-Ling Lin,Jian-Min Zhang 한국물리학회 2019 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.74 No.6

Using rst-principles calculations, we have systematically investigated the structural stability and the electronic and optical properties of bimetallic AgAu, CuAu, and CuAg (4; 2) alloy nanotubes (NTs). We found that the tip-suspended AgAu and CuAu alloy NTs were stable structures due to the existence of local minima in both the binding energies and the string tensions variation with their unit-cell lengths and that the stability was enhanced when the content of Au was increased. However, a tip-suspended CuAg alloy NT would be difficult to form in future experiments. We also found that both the relativistic effect of elemental gold and the string tension applied by the tip contacts play important roles in suppressing effectively the self-purication effect, leading to the formation of these coinage alloy NTs. The quantum conductance of the stable alloy NTs is increased by 1G0 as compared with that of the corresponding pure coinage-metal NTs.

Effects of Glucagon-Like Peptide-2-Expressing Saccharomyces cerevisiae Not Different from Empty Vector

( Xi Zhong ),( Guopeng Liang ),( Lili Cao ),( Qi Qiao ),( Zhi Hu ),( Min Fu ),( Hong Bo ),( Qin Wu ),( Guanlin Liang ),( Zhongwei Zhang ),( Lin Zhou ) 한국미생물생명공학회(구 한국산업미생물학회) 2019 Journal of microbiology and biotechnology Vol.29 No.10

Saccharomyces cerevisiae (S. cerevisiae) and glucagon-like peptide-2 (GLP-2) have been employed to improve the intestinal development of weaned animals. The goal of this study was to determine whether either exogenous S. cerevisiae or GLP-2 elicits major effects on fecal microbiotas and cytokine responses in weaned piglets. Ninety-six piglets weaned at 26 days were assigned to one of four groups: 1) Basal diet (Control), 2) empty vector-harboring S. cerevisiae (EV-SC), 3) GLP-2-expressing S. cerevisiae (GLP2-SC), and 4) recombinant human GLP-2 (rh-GLP2). At the start of the post-weaning period (day 0), and at day 28, fecal samples were collected to assess the bacterial communities via sequencing the V1-V2 region of the 16SrRNA gene, and piglets’ blood was also sampled to measure cytokine responses (i.e., IL-1β, TNF-α, and IFN-γ). This study revealed that, on the one hand, although S. cerevisiae supplementation did not significantly alter the growth of weaned piglets, it induced increases in the relative abundances of two core genera (Ruminococcaceae_norank and Erysipelotrichaceae_norank) and decreases in the relative abundances of two other core genera (Lachnospiraceae_norank and Clostridiale_norank) and cytokine levels (IL-1β and TNF-α) (p < 0.05, Control vs EV-SC; p < 0.05, rh-GLP2 vs GLP2-SC). On the other hand, GLP-2 supplementation had no significant influence on fecal bacterial communities and cytokine levels, but it produced better body weight and average daily gain (p < 0.05, Control vs EV-SC; p < 0.05, rh-GLP2 vs GLP2-SC). Therefore, altered fecal microbiotas and cytokine response effects in weaned piglets were due to S. cerevisiae rather than GLP-2.

Recombinant Human Thioredoxin-1 Protects Macrophages from Oxidized Low-Density Lipoprotein-Induced Foam Cell Formation and Cell Apoptosis

Zhang, Hui,Liu, Qi,Lin, Jia-Le,Wang, Yu,Zhang, Ruo-Xi,Hou, Jing-Bo,Yu, Bo The Korean Society of Applied Pharmacology 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.2

Oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation and apoptosis play critical roles in the pathogenesis of atherosclerosis. Thioredoxin-1 (Trx) is an antioxidant that potently protects various cells from oxidative stress-induced cell death. However, the protective effect of Trx on ox-LDL-induced macrophage foam cell formation and apoptosis has not been studied. This study aims to investigate the effect of recombinant human Trx (rhTrx) on ox-LDL-stimulated RAW264.7 macrophages and elucidate the possible mechanisms. RhTrx significantly inhibited ox-LDL-induced cholesterol accumulation and apoptosis in RAW264.7 macrophages. RhTrx also suppressed the ox-LDL-induced overproduction of lectin-like oxidized LDL receptor (LOX-1), Bax and activated caspase-3, but it increased the expression of Bcl-2. In addition, rhTrx markedly inhibited the ox-LDL-induced production of intracellular reactive oxygen species (ROS) and phosphorylation of p38 mitogen-activated protein kinases (MAPK). Furthermore, anisomycin (a p38 MAPK activator) abolished the protective effect of rhTrx on ox-LDL-stimulated RAW264.7 cells, and SB203580 (a p38 MAPK inhibitor) exerted a similar effect as rhTrx. Collectively, these findings indicate that rhTrx suppresses ox-LDL-stimulated foam cell formation and macrophage apoptosis by inhibiting ROS generation, p38 MAPK activation and LOX-1 expression. Therefore, we propose that rhTrx has therapeutic potential in the prevention and treatment of atherosclerosis.

Effective and Secure Access Control for Multi-Authority Cloud Storage Systems

Lin Xin,Xingming Sun,Zhangjie Fu,Liang-Ao Zhang,Jie Xi 보안공학연구지원센터 2016 International Journal of Security and Its Applicat Vol.10 No.2

Ciphertext-Policy Attribute-Based Encryption (CP-ABE) is a promising cryptographic tool to implement access control for secure cloud storage systems. However, most existing access control schemes based on CP-ABE for the multi-authority cloud storage systems rely on a fully trusted global certificate authority. It is just an ideal assumption while there never exists a fully trusted global certificate authority in reality. In this paper, we construct a system with multiple certificate authorities (CA). The parameters of those CAs could be verified when an authority suspects the messages received from the correlative certificate authority. Besides, we construct a verifiable secret sharing (VSS) scheme to realize the decentralization of the certificate authority in our scheme. The scheme adopts the Pedersen commitment in combination with the properties of bilinear-pairs on elliptic curve and bilinear Diffie-Hellman problem. The analysis shows that our scheme is highly efficient, authentic and provably secure under the security model. Our scheme simultaneously supports efficient attribute revocation.

Apoptosis Induction Effects of EGCG in Laryngeal Squamous Cell Carcinoma Cells through Telomerase Repression

Xi Wang,Miao-Wang Hao,Ke Dong,Fang Lin,Ji-Hong Ren,Hui-Zhong Zhang 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.9

Epigallocatechin-3-gallate (EGCG), the major component of green tea polyphenol, has potent efficiency to prevent the growth of a variety of cancer cells. As a novel anticancer agent for treatment of cancers, EGCG is promising and the mechanism has not been fully understood. Laryngeal squamous cell carcinoma (LSCC) is one common tumor in head and neck cancers. In the present study, we assess the effects of EGCG on LSCC cell line Hep-2, and their possible involvement in EGCG-induced apoptosis. The result showed that treatment of Hep-2 cells with EGCG decreased the cell viability, inhibited the growth and proliferation, induced apoptosis and increased the activity of caspase-3 in a dose-dependent manner. Furthermore, we found that EGCG-treatment repressed telomerase activity effectively in a concentrationdependent manner. The combined results show that EGCG induced apoptosis in Hep-2 cells via inhibiting the telomerase activity.

Prolyl endopeptidase remodels macrophage function as a novel transcriptional coregulator and inhibits fibrosis

Lin Shuang-Zhe,Wu Wei-Jie,Cheng Yu-Qing,Zhang Jian-Bin,Jiang Dai-Xi,Ren Tian-Yi,Ding Wen-Jin,Liu Mingxi,Chen Yuan-Wen,Fan Jian-Gao 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Macrophages are immune cells crucial for host defense and homeostasis maintenance, and their dysregulation is involved in multiple pathological conditions, such as liver fibrosis. The transcriptional regulation in macrophage is indispensable for fine-tuning of macrophage functions, but the details have not been fully elucidated. Prolyl endopeptidase (PREP) is a dipeptidyl peptidase with both proteolytic and non-proteolytic functions. In this study, we found that Prep knockout significantly contributed to transcriptomic alterations in quiescent and M1/M2-polarized bone marrow-derived macrophages (BMDMs), as well as aggravated fibrosis in an experimental nonalcoholic steatohepatitis (NASH) model. Mechanistically, PREP predominantly localized to the macrophage nuclei and functioned as a transcriptional coregulator. Using CUT&Tag and co-immunoprecipitation, we found that PREP was mainly distributed in active cis-regulatory genomic regions and physically interacted with the transcription factor PU.1. Among PREP-regulated downstream genes, genes encoding profibrotic cathepsin B and D were overexpressed in BMDMs and fibrotic liver tissue. Our results indicate that PREP in macrophages functions as a transcriptional coregulator that finely tunes macrophage functions, and plays a protective role against liver fibrosis pathogenesis.

Histological Validation of Cardiovascular Magnetic Resonance T1 Mapping for Assessing the Evolution of Myocardial Injury in Myocardial Infarction: An Experimental Study

Zhang Lu,Yang Zhi-gang,Xu Huayan,Yang Meng-xi,Xu Rong,Chen Lin,Sun Ran,Miao Tianyu,Zhao Jichun,Zhou Xiaoyue,Fu Chuan,Guo Yingkun 대한영상의학회 2020 Korean Journal of Radiology Vol.21 No.12

Objective: To determine whether T1 mapping could monitor the dynamic changes of injury in myocardial infarction (MI) and be histologically validated. Materials and Methods: In 22 pigs, MI was induced by ligating the left anterior descending artery and they underwent serial cardiovascular magnetic resonance examinations with modified Look-Locker inversion T1 mapping and extracellular volume (ECV) computation in acute (within 24 hours, n = 22), subacute (7 days, n = 13), and chronic (3 months, n = 7) phases of MI. Masson’s trichrome staining was performed for histological ECV calculation. Myocardial native T1 and ECV were obtained by region of interest measurement in infarcted, peri-infarct, and remote myocardium. Results: Native T1 and ECV in peri-infarct myocardium differed from remote myocardium in acute (1181 ± 62 ms vs. 1113 ± 64 ms, p = 0.002; 24 ± 4% vs. 19 ± 4%, p = 0.031) and subacute phases (1264 ± 41 ms vs. 1171 ± 56 ms, p < 0.001; 27 ± 4% vs. 22 ± 2%, p = 0.009) but not in chronic phase (1157 ± 57 ms vs. 1120 ± 54 ms, p = 0.934; 23 ± 2% vs. 20 ± 1%, p = 0.109). From acute to chronic MI, infarcted native T1 peaked in subacute phase (1275 ± 63 ms vs. 1637 ± 123 ms vs. 1471 ± 98 ms, p < 0.001), while ECV progressively increased with time (35 ± 7% vs. 46 ± 6% vs. 52 ± 4%, p < 0.001). Native T1 correlated well with histological findings (R2 = 0.65 to 0.89, all p < 0.001) so did ECV (R2 = 0.73 to 0.94, all p < 0.001). Conclusion: T1 mapping allows the quantitative assessment of injury in MI and the noninvasive monitoring of tissue injury evolution, which correlates well with histological findings.

Recombinant Human Thioredoxin-1 Protects Macrophages from Oxidized Low-Density Lipoprotein-Induced Foam Cell Formation and Cell Apoptosis

( Hui Zhang ),( Qi Liu ),( Jia-le Lin ),( Yu Wang ),( Ruo-xi Zhang ),( Jing-bo Hou ),( Bo Yu ) 한국응용약물학회 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.2

Oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation and apoptosis play critical roles in the pathogenesis of atherosclerosis. Thioredoxin-1 (Trx) is an antioxidant that potently protects various cells from oxidative stress-induced cell death. However, the protective effect of Trx on ox-LDL-induced macrophage foam cell formation and apoptosis has not been studied. This study aims to investigate the effect of recombinant human Trx (rhTrx) on ox-LDL-stimulated RAW264.7 macrophages and elucidate the possible mechanisms. RhTrx significantly inhibited ox-LDL-induced cholesterol accumulation and apoptosis in RAW264.7 macrophages. RhTrx also suppressed the ox-LDL-induced overproduction of lectin-like oxidized LDL receptor (LOX- 1), Bax and activated caspase-3, but it increased the expression of Bcl-2. In addition, rhTrx markedly inhibited the ox-LDL-induced production of intracellular reactive oxygen species (ROS) and phosphorylation of p38 mitogen-activated protein kinases (MAPK). Furthermore, anisomycin (a p38 MAPK activator) abolished the protective effect of rhTrx on ox-LDL-stimulated RAW264.7 cells, and SB203580 (a p38 MAPK inhibitor) exerted a similar effect as rhTrx. Collectively, these findings indicate that rhTrx suppresses ox-LDL-stimulated foam cell formation and macrophage apoptosis by inhibiting ROS generation, p38 MAPK activation and LOX-1 expression. Therefore, we propose that rhTrx has therapeutic potential in the prevention and treatment of atherosclerosis.