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Acta Pharmacologica Sinica

Qing Li, Ting-Ting Tang, Feng Jiang, Rong Zhang, Miao Chen, Jun Yin, Yu-Qian Bao, Xiang Cheng, Cheng Hu, Wei-Ping Jia
AIM: KCNQ1 channel is a member of the voltage-gated potassium channel KQT-like subfamily. The KCNQ1 gene has recently been identified as a susceptibility locus for type 2 diabetes mellitus (T2DM). In the present study, we examined the effects of KCNQ1 variants on the therapeutic response to modified-release gliclazide (gliclazide MR) treatment in Chinese patients newly diagnosed with T2DM. METHODS: A total of 100 newly diagnosed T2DM patients without a history of any anti-diabetic medications were treated with gliclazide MR for 16 weeks, but 91 patients completed the entire study...
October 3, 2016: Acta Pharmacologica Sinica
Huan Wang, Hong-Fei Wang, Hao Zhang, Chen Wang, Yu-Fang Chen, Rong Ma, Ji-Zhou Xiang, Xin-Ling Du, Qiang Tang
AIM: Voltage-gated sodium channels composed of a pore-forming α subunit and auxiliary β subunits are responsible for the upstroke of the action potential in cardiac myocytes. The pore-forming subunit of the cardiac sodium channel Nav1.5, which is encoded by SCN5A, is the main ion channel that conducts the voltage-gated cardiac sodium current (INa) in cardiac cells. The current study sought to investigate the inhibitory effects of hesperetin (HSP) on human cardiac Nav1.5 channels stably expressed in human embryonic kidney 293 (HEK 293) cells and on the voltage-gated cardiac sodium current (INa) in human atrial myocytes...
October 3, 2016: Acta Pharmacologica Sinica
Cong Li, Xiao-Dan Guo, Min Lei, Jia-Yi Wu, Jia-Zhen Jin, Xiao-Fan Shi, Zhi-Yuan Zhu, Vatcharin Rukachaisirikul, Li-Hong Hu, Tie-Qiao Wen, Xu Shen
AIM: Considering the complicated pathogenesis of Alzheimer's disease (AD), multi-targets have become a focus in the discovery of drugs for treatment of this disease. In the current work, we established a multi-target strategy for discovering active reagents capable of suppressing both Aβ level and Tau hyperphosphorylation from natural products, and found that the ethanol extract of Thamnolia vermicularis (THA) was able to improve learning ability in APP/PS1 transgenic mice by inhibiting both Aβ levels and Tau hyperphosphorylation...
October 3, 2016: Acta Pharmacologica Sinica
Ming-Jie Pang, Zhun Yang, Xing-Lin Zhang, Zhao-Fang Liu, Jun Fan, Hong-Ying Zhang
AIM: Physcion is a major bioactive ingredient in the traditional Chinese medicine Radix et Rhizoma Rhei, which has an anthraquinone chemical structure and exhibits a variety of pharmacological activities including laxative, hepatoprotective, anti-inflammatory, anti-microbial and anti-proliferative effects. In this study we investigated the effect of physcion on human nasopharyngeal carcinoma in vitro and in vivo, as well as the mechanisms underlying the anti-tumor action. METHODS: The nasopharyngeal carcinoma cell line CNE2 was treated with physcion, and cell viability was detected using MTT and colony formation assays...
October 3, 2016: Acta Pharmacologica Sinica
Hao Huang, Qian Hong, Hong-Ling Tan, Cheng-Rong Xiao, Yue Gao
AIM: Phosphodiesterase 4 (PDE4) isozymes are involved in different functions, depending on their patterns of distribution in the brain. The PDE4 subtypes are distributed in different inflammatory cells, and appear to be important regulators of inflammatory processes. In this study we examined the effects of ferulic acid (FA), a plant component with strong anti-oxidant and anti-inflammatory activities, on lipopolysaccharide (LPS)-induced up-regulation of phosphodiesterase 4B (PDE4B) in PC12 cells, which in turn regulated cellular cAMP levels and the cAMP/cAMP response element binding protein (CREB) pathway in the cells...
September 26, 2016: Acta Pharmacologica Sinica
Qi Pei, Lu Huang, Jie Huang, Jing-Kai Gu, Yun Kuang, Xiao-Cong Zuo, Jun-Jie Ding, Hong-Yi Tan, Cheng-Xian Guo, Shi-Kun Liu, Guo-Ping Yang
AIM: Iloperidone is an atypical antipsychotic drug that is mainly metabolized by CYP2D6, CYP3A4, and cytosolic enzymes. Previous studies show that extensive and poor metabolizers of CYP2D6 exhibit different plasma concentrations of iloperidone and its metabolites. The aim of this study was to develop a parent-metabolite population pharmacokinetic (PPK) model to quantify the effects of CYP2D6(*)10 allele on the pharmacokinetics of iloperidone and its metabolites in Chinese schizophrenia patients...
September 26, 2016: Acta Pharmacologica Sinica
Ji Zhang, Yi-Rong Ding, Rui Wang
AIM: Tissue transglutaminase (tTG) catalyzes proteins, including β-amyloid (Aβ), to cross-link as a γ-glutamyl-ε-lysine structure isopeptide, which is highly resistant to proteolysis. Thus, tTG plays an important role in protein accumulation in Alzheimer's disease (AD). In the present study, we examined the effect of an irreversible tTG inhibitor, NTU283, on Aβ mimic-induced AD pathogenesis in SH-SY5Y cells. METHODS: Western blot and in-cell Western analyses were used to detect tTG and isopeptide (representing the enzyme activity of tTG) protein levels...
September 26, 2016: Acta Pharmacologica Sinica
Tian-Qing Chu, Rong Li, Min-Hua Shao, Jun-Yi Ye, Bao-Hui Han
AIM: Although targeted therapy is very efficient for lung cancer, traditional platinum-based chemotherapies are still the principal strategy in the absence of positive biomarkers. The aim of the present study is to evaluate the contribution of RAD18 polymorphisms to platinum-chemotherapy response and its potential side effects in Chinese patients with non-small cell lung cancer (NSCLC). METHODS: A total of 1021 Chinese patients with histological diagnosis of advanced NSCLC were enrolled...
September 26, 2016: Acta Pharmacologica Sinica
Dan Zhang, Bo Zhang, Li-Xin Zhou, Jun Zhao, You-You Yan, Yang-Ling Li, Jian-Mei Zeng, Lin-Ling Wang, Bo Yang, Neng-Ming Lin
AIM: Deacetylisovaltratum (DI) is isolated from the traditional Chinese herbal medicine Patrinia heterophylla Bunge, which exhibits anti-cancer activity. Here, we investigated the effects of DI on human gastric carcinoma cell lines in vitro and elucidated its anti-cancer mechanisms. METHODS: Human gastric carcinoma AGS and HGC-27 cell lines were treated with DI, and cell viability was detected with MTT assay. Cell cycle stages, apoptosis and mitochondrial membrane potential were measured using flow cytometry...
September 26, 2016: Acta Pharmacologica Sinica
Ling-Ling Peng, Yuan-Qi Zhao, Zi-Yi Zhou, Jing Jin, Min Zhao, Xin-Meng Chen, Ling-Yan Chen, Ye-Feng Cai, Jia-Li Li, Min Huang
AIM: Aspirin resistance has an incidence of 5%-65% in patients with ischemic stroke, who receive the standard dose of aspirin, but the platelet function is inadequately inhibited, thereby leading to thrombotic events. Numerous evidence shows that thromboxane A2 receptor (TXA2 receptor, encoded by TBXA2R), lipoprotein-associated phospholipase A2 (Lp-PLA2, encoded by PLA2G7) and platelet endothelial aggregation receptor-1 (PEAR1, encoded by PEAR1) are crucial in regulating platelet activation, and P-glycoprotein (P-gp, encoded by MDR1) influences the absorption of aspirin in the intestine...
September 19, 2016: Acta Pharmacologica Sinica
Cheng-Gang Li, Meng-Fan Pu, Chun-Zhu Li, Man Gao, Ming-Xia Liu, Cun-Zhi Yu, Hong Yan, Chun Peng, Yang Zhao, Yu Li, Ze-Long Ma, Xin-Ming Qi, Yi-Zheng Wang, Ling-Ling Miao, Jin Ren
AIM: Previous studies have shown that microRNA-1304 (miR-1304) is dysregulated in certain types of cancers, including non-small cell lung cancer (NSCLC), and might be involved in tumor survival and/or growth. In this study we investigated the direct target of miR-1304 and its function in NSCLC in vitro. METHODS: Human lung adenocarcinoma cell lines (A549 and NCI-H1975) were studied. The cell proliferation and survival were investigated via cell counting, MTT and colony-formation assays...
September 19, 2016: Acta Pharmacologica Sinica
Li-Yun Yang, Xiao-Fang Liu, Yang Yang, Lin-Lin Yang, Kai-Wen Liu, Yu-Bo Tang, Min Zhang, Min-Jia Tan, Shan-Mei Cheng, Ye-Chun Xu, Huai-Yu Yang, Zhi-Jie Liu, Gao-Jie Song, Wei Huang
AIM: CD97 belongs to the adhesion GPCR family characterized by a long ECD linked to the 7TM via a GPCR proteolytic site (GPS) and plays important roles in modulating cell migration and invasion. CD97 (EGF1-5) is a splicing variant of CD97 that recognizes a specific ligand chondroitin sulfate on cell membranes and the extracellular matrix. The aim of this study was to elucidate the extracellular molecular basis of the CD97 EGF1-5 isoform in protein expression, auto-proteolysis and cell adhesion, including epidermal growth factor (EGF)-like domain, GPCR autoproteolysis-inducing (GAIN) domain, as well as GPS mutagenesis and N-glycosylation...
September 19, 2016: Acta Pharmacologica Sinica
Zheng Mou, Yu-He Yuan, Yu-Xia Lou, Yang Heng, Ju-Yang Huang, Cong-Yuan Xia, Yan Gao, Cheng-Gen Zhu, Shi-Feng Chu, Piao Luo, Jian-Gong Shi, Nai-Hong Chen
AIM: Accumulation of α-synuclein (α-syn) in the brain is a characteristic of Parkinson's disease (PD). In this study, we investigated whether treatment with tunicamycin, an endoplasmic reticulum (ER) stress inducer, led to the accumulation of α-syn in PC12 cells, and where α-syn protein was accumulated, and, finally, whether bibenzyl compound 20c, a novel compound isolated from Gastrodia elata (Tian ma), could alleviate the accumulation of α-syn and ER stress activation in tunicamycin-treated PC12 cells...
September 12, 2016: Acta Pharmacologica Sinica
Lu Gan, Zhen-Hua Wang, Hong Zhang, Xin Zhou, Hui Zhou, Chao Sun, Jing Si, Rong Zhou, Cheng-Jun Ma, Ji Li
AIM: Ginsenosides are considered to be the major pharmacologically active ginseng constituents, whereas 20(S)-protopanaxadiol [20(S)-PPD] is the active metabolite of ginsenosides in gut. In this study we investigated the effect of 20(S)-PPD on isolated rat thoracic aortas as well as its vasorelaxant mechanisms. METHODS: Aortic rings with or without endothelium were prepared from Wistar rats and suspended in organ-chambers. The changes in tension of the preparations were recorded through isometric transducers connected to a data acquisition system...
September 12, 2016: Acta Pharmacologica Sinica
Yue-Qin Wang, Ai-Jun Shen, Jing-Ya Sun, Xin Wang, Hong-Chun Liu, Min-Min Zhang, Dan-Qi Chen, Bing Xiong, Jing-Kang Shen, Mei-Yu Geng, Min Zheng, Jian Ding
AIM: Inhibition of heat shock protein (Hsp90) has been proven to be effective in overriding primary and acquired resistance of kinase inhibitors. In this study, we investigated the role of FS-108, a newly developed Hsp90 inhibitor, to overcome gefitinib resistance in EGFR mutant non-small cell lung cancer cells. METHODS: Cell proliferation was assessed using the SRB assay. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Protein expression was examined by Western blotting...
September 12, 2016: Acta Pharmacologica Sinica
Xiao-Qin Lv, Xin-Ran Qiao, Ling Su, Shu-Zhen Chen
AIM: Honokiol (HNK) is a natural compound isolated from the magnolia plant with numerous pharmacological activities, including inhibiting epithelial-mesenchymal transition (EMT), which has been proposed as an attractive target for anti-tumor drugs to prevent tumor migration. In this study we investigated the effects of HNK on EMT in human NSCLC cells in vitro and the related signaling mechanisms. METHODS: TNF-α (25 ng/mL) in combination with TGF-β1 (5 ng/mL) was used to stimulate EMT of human NSCLC A549 and H460 cells...
September 5, 2016: Acta Pharmacologica Sinica
Min Wu, Ri-Ning Tang, Hong Liu, Ming-Ming Pan, Bi-Cheng Liu
AIM: Experimental studies found that cinacalcet (CINA) markedly attenuated vascular calcification in uremic rats, but its underlying mechanisms are still largely unknown. Recent evidence have demonstrated that endothelial cells (ECs) participate in ectopic calcification in part by mediating endothelial-to-mesenchymal transition (EndMT). In this study, we investigated whether CINA ameliorated aortic calcification in uremic rats via suppression of EndMT. METHODS: Uremia was induced in rats by feeding rats a 0...
September 5, 2016: Acta Pharmacologica Sinica
Bang-Wei Yu, Jin-Long Li, Bin-Bin Guo, Hui-Min Fan, Wei-Min Zhao, He-Yao Wang
AIM: Chlorogenic acid has shown protective effect on cardiomyocytes against oxidative stress-induced damage. Herein, we evaluated nine caffeoylquinic acid analogues (1-9) isolated from the leaves of Gynura nepalensis for their protective effect against H2O2-induced H9c2 cardiomyoblast damage and explored the underlying mechanisms. METHODS: H9c2 cardiomyoblasts were exposed to H2O2 (0.3 mmol/L) for 3 h, and cell viability was detected with MTT assay. Hoechst 33342 staining was performed to evaluate cell apoptosis...
September 5, 2016: Acta Pharmacologica Sinica
Shao Xie, Hui Jiang, Xiao-Wen Zhai, Fan Wei, Shu-Dong Wang, Jian Ding, Yi Chen
AIM: LS-007 is a CDK inhibitor, which exhibits potent antitumor activity against chronic lymphocytic leukemia and ovarian cancer cells. In this study, we further evaluated the antitumor activity of LS-007 alone and in combination with a Bcl-2 inhibitor ABT-199 in acute leukemia (AL) cells. METHODS: Cell viability was detected using resazurin assay, and cell apoptosis was examined using Annexin V/PI double staining and flow cytometry. The inhibition of LS-007 on kinases was evaluated with the mobility shift assay or ELISA...
August 29, 2016: Acta Pharmacologica Sinica
Thu Ngo, Xin Miao, Douglas N Robinson, Qiong-Qiong Zhou
AIM: RNA-binding proteins are a large group of regulators (800-1000 in humans), some of which play significant roles in mRNA local translation. In this study, we analyzed the functions of the protein RNP-1, which was previously discovered in a genetic selection screen for nocodazole suppression. METHODS: The growth rates and the microtubule networks of Dictyostelium cells were assessed with or without nocodazole (10 μmol/L) in suspension culture. Fluorescent images of RNP-1-GFP and RFP-tubulin were captured when cells were undergoing cytokinesis, then the GFP signal intensity and distance to the nearest centrosome were analyzed by using a computer program written in Matlab(®)...
August 29, 2016: Acta Pharmacologica Sinica
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