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Acta Pharmacologica Sinica

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https://www.readbyqxmd.com/read/28933425/carnosine-suppresses-oxygen-glucose-deprivation-recovery-induced-proliferation-and-migration-of-reactive-astrocytes-of-rats-in-vitro
#1
Li Ou-Yang, Yuan Liu, Bing-Yu Wang, Pei Cao, Jing-Jing Zhang, Yu-Yan Huang, Yao Shen, Jian-Xin Lyu
Glial scar formation resulted from excessive astrogliosis limits axonal regeneration and impairs recovery of function, thus an intervention to ameliorate excessive astrogliosis is crucial for the recovery of neurological function after cerebral ischemia. In this study we investigated the effects of carnosine, an endogenous water-soluble dipeptide (β-alanyl-L-histidine), on astrogliosis of cells exposed to oxygen-glucose deprivation/recovery (OGD/R) in vitro. Primary cultured rat astrocytes exhibited a significant increase in proliferation at 24 h recovery after OGD for 2 h...
September 21, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28933424/the-efficacy-and-safety-of-cilostazol-as-an-alternative-to-aspirin-in-chinese-patients-with-aspirin-intolerance-after-coronary-stent-implantation-a-combined-clinical-study-and-computational-system-pharmacology-analysis
#2
Ying Xue, Zhi-Wei Feng, Xiao-Ye Li, Zi-Heng Hu, Qing Xu, Zi Wang, Jia-Hui Cheng, Hong-Tao Shi, Qi-Bing Wang, Hong-Yi Wu, Xiang-Qun Xie, Qian-Zhou Lv
Dual antiplatelet therapy (DAT) with aspirin and clopidogrel is the standard regimen to achieve rapid platelet inhibition and prevent thrombotic events. Currently, little information is available regarding alternative antiplatelet therapy in patients with an allergy or intolerance to aspirin. Although cilostazol is already a common alternative to aspirin in clinical practice in China, its efficacy and safety remain to be determined. We retrospectively analyzed 613 Chinese patients who had undergone primary percutaneous coronary intervention (PCI)...
September 21, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28933423/omega-3-pufa-ameliorates-hyperhomocysteinemia-induced-hepatic-steatosis-in-mice-by-inhibiting-hepatic-ceramide-synthesis
#3
Yong-Qiang Dong, Xing-Zhong Zhang, Lu-Lu Sun, Song-Yang Zhang, Bo Liu, Hui-Ying Liu, Xian Wang, Chang-Tao Jiang
Hyperhomocysteinemia (HHcy) is a key risk factor in hepatic steatosis. In this study, we applied a metabolomic approach to investigate the changes in the metabolite profile due to HHcy-induced hepatic steatosis and the effects of omega-3 PUFA (polyunsaturated fatty acid) supplementation in mice. HHcy was induced in mice by giving DL-Hcy (1.8 g/L) in drinking water for 6 weeks, then the mice were sacrificed, and the metabolic profiles of the liver and plasma were analyzed through UPLC-ESI-QTOFMS-based lipidomics...
September 21, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28905939/curcumin-administration-suppresses-collagen-synthesis-in-the-hearts-of-rats-with-experimental-diabetes
#4
Shuang Guo, Xiang-Wen Meng, Xiao-Song Yang, Xiu-Fen Liu, Chang-Han Ou-Yang, Chao Liu
Cardiac fibrosis is considered the initial change of diabetic cardiomyopathy (DCM). We have shown that curcumin alleviates collagen deposition in DCM, but the mechanism remains unknown. In this study we sought to investigate the effects of curcumin on cardiac fibrosis in vivo and in vitro and to elucidate the underlying mechanisms. Experimental diabetes was induced in rats by injection of low-dose streptozotocin (STZ) combined with high energy diet. The rats were orally treated with curcumin (300 mg·kg(-1)·d(-1)) for 16 weeks...
September 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28905938/triptolide-induces-sertoli-cell-apoptosis-in-mice-via-ros-jnk-dependent-activation-of-the-mitochondrial-pathway-and-inhibition-of-nrf2-mediated-antioxidant-response
#5
Yu Wang, Su-Han Guo, Xue-Jun Shang, Li-Sha Yu, Jian-Wei Zhu, Ang Zhao, Yan-Fen Zhou, Guo-Hua An, Qi Zhang, Bo Ma
Triptolide (TP), an oxygenated diterpene, has a variety of beneficial pharmacodynamic activities but its clinical applications are restricted due to severe testicular injury. This study aimed to delineate the molecular mechanisms of TP-induced testicular injury in vitro and in vivo. TP (5-50000 nmol/L) dose-dependently decreased the viability of TM4 Sertoli cells with an IC50 value of 669.5-269.45 nmol/L at 24 h. TP (125, 250, and 500 nmol/L) dose-dependently increased the accumulation of ROS, the phosphorylation of JNK, mitochondrial dysfunction and activation of the intrinsic apoptosis pathway in TM4 cells...
September 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28905937/somcl-085-a-novel-multi-targeted-fgfr-inhibitor-displays-potent-anticancer-activity-in-fgfr-addicted-human-cancer-models
#6
Xi-Fei Jiang, Yang Dai, Xia Peng, Yan-Yan Shen, Yi Su, Man-Man Wei, Wei-Ren Liu, Zhen-Bin Ding, Ao Zhang, Ying-Hong Shi, Jing Ai
Aberrant fibroblast growth factor receptor (FGFR) activation is found across a diverse spectrum of malignancies, especially those lacking effective treatments. SOMCL-085 is a novel FGFR-dominant multi-target kinase inhibitor. Here, we explored the FGFR-targeting anticancer activity of SOMCL-085 both in vitro and in vivo. Among a panel of 20 tyrosine kinases screened, SOMCL-085 potently inhibited FGFR1, FGFR2 and FGFR3 kinase activity, with IC50 values of 1.8, 1.9 and 6.9 nmol/L, respectively. This compound simultaneously inhibited the angiogenesis kinases VEGFR and PDGFR, but without obvious inhibitory effect on other 12 tyrosine kinases...
September 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28905936/combing-oncolytic-adenovirus-expressing-beclin-1-with-chemotherapy-agent-doxorubicin-synergistically-enhances-cytotoxicity-in-human-cml-cells-in-vitro
#7
Li Li, Liang-Shun You, Li-Ping Mao, Shen-He Jin, Xiao-Hui Chen, Wen-Bin Qian
Cancer virotherapy provides a new strategy to treat cancer that can directly kill cancer cells by oncolysis. Insertion of therapeutic genes into the genome of a modified adenovirus, thereby creating a so-called gene-virotherapy that shares the advantages of gene therapy and virotherapy. In this study we investigated whether a strategy that combines the oncolytic effects of an adenoviral vector with the simultaneous expression of the autophagy gene Beclin-1 offered a therapeutic advantage for chronic myeloid leukemia (CML) cells with resistance to chemotherapy and evaluated the synergistic effects of SG511-BECN and doxorubicin (Dox) in human CML cells in vitro...
September 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28905935/age-related-differences-in-interferon-regulatory-factor-4-and-5-signaling-in-ischemic-brains-of-mice
#8
Shou-Cai Zhao, Chun Wang, Heng Xu, Wen-Qian Wu, Zhao-Hu Chu, Ling-Song Ma, Ying-Dong Zhang, Fudong Liu
Stroke is a disease that mainly affects the elderly. Since the age-related differences in stroke have not been well studied, modeling stroke in aged animals is clinically more relevant. The inflammatory responses to stroke are a fundamental pathological procedure, in which microglial activation plays an important role. Interferon regulatory factor-5 (IRF5) and IRF4 regulate M1 and M2 activation of macrophages, respectively, in peripheral inflammation; but it is unknown whether IRF5/IRF4 are also involved in cerebral inflammatory responses to stroke and whether age-related differences of the IRF5/IRF4 signaling exist in ischemic brain...
September 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28905934/conversion-and-pharmacokinetics-profiles-of-a-novel-pro-drug-of-3-n-butylphthalide-potassium-2-1-hydroxypentyl-benzoate-in-rats-and-dogs
#9
Jiang Li, Shao-Feng Xu, Ying Peng, Nan Feng, Ling Wang, Xiao-Liang Wang
Potassium 2-(1-hydroxypentyl)-benzoate (dl-PHPB) is a novel pro-drug of 3-n-butylphthalide (dl-NBP) that is used to treat ischemic stroke. Currently, dl-PHPB is in phase II-III clinical trials in China. In this study, we investigated the conversion and pharmacokinetics profiles of dl-PHPB in vitro and in vivo. The conversion of dl-PHPB to dl-NBP was pH- and calcium-dependent, and paraoxonase was identified as a major enzyme for the conversion in rat plasma. The pharmacokinetics, tissue distribution and excretion of dl-PHPB were studied and compared with equal-molar doses of dl-NBP in rats and dogs...
September 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28880016/-5r-5-hydroxytriptolide-ameliorates-anti-glomerular-basement-membrane-glomerulonephritis-in-nzw-mice-by-regulating-fc%C3%AE-receptor-signaling
#10
Qing Qi, Heng Li, Ze-Min Lin, Xiao-Qian Yang, Feng-Hua Zhu, Yu-Ting Liu, Mei-Juan Shao, Lu-Yao Zhang, Yan-Sheng Xu, Yu-Xi Yan, Lan-Lan Sun, Shi-Jun He, Wei Tang, Jian-Ping Zuo
(5R)-5-hydroxytriptolide (LLDT-8) is a novel triptolide analog that has been identified as a promising candidate for treating autoimmune diseases and has been shown to be effective in treating murine collagen-induced arthritis and lupus nephritis. In the present study, we investigated the therapeutic effect and possible mechanism of action of LLDT-8 in a murine anti-glomerular basement membrane (GBM) glomerulonephritis model. NZW mice were injected with rabbit anti-GBM serum (500 μL, ip). The mice were orally treated with LLDT-8 (0...
September 7, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28880015/integrated-pharmacokinetic-viral-dynamic-model-for-daclatasvir-asunaprevir-in-treatment-of-patients-with-genotype-1-chronic-hepatitis-c
#11
He-Chuan Wang, Yu-Peng Ren, Yue Qiu, Jenny Zheng, Gai-Ling Li, Chuan-Pu Hu, Tian-Yan Zhou, Wei Lu, Liang Li
In order to develop an integrated pharmacokinetic/viral dynamic (PK/VD) model to predict long-term virological response rates to daclatasvir (DCV) and asunaprevir (ASV) combination therapy in patients infected with genotype 1 (GT1) chronic hepatitis C virus (HCV), a systematic publication search was conducted for DCV and ASV administered alone and/or in combination in healthy subjects or patients with GT1 HCV infection. On the basis of a constructed meta-database, an integrated PK/VD model was developed, which adequately described both DCV and ASV PK profiles and viral load time curves...
September 7, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28880014/chimeric-antigen-receptor-car-transduced-natural-killer-cells-in-tumor-immunotherapy
#12
REVIEW
Yuan Hu, Zhi-Gang Tian, Cai Zhang
Natural killer (NK) cells are potential effector cells in cell-based cancer immunotherapy, particularly in the control of hematological malignancies. The chimeric antigen receptor (CAR) is an artificially modified fusion protein that consists of an extracellular antigen recognition domain fused to an intracellular signaling domain. T cells genetically modified with a CAR have demonstrated remarkable success in the treatment of hematological cancers. Compared to T cells, CAR-transduced NK cells (CAR-NK) exhibit several advantages, such as safety in clinical use, the mechanisms by which they recognize cancer cells, and their abundance in clinical samples...
September 7, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28880013/osimertinib-azd9291-decreases-programmed-death-ligand-1-in-egfr-mutated-non-small-cell-lung-cancer-cells
#13
Xiao-Ming Jiang, Yu-Lian Xu, Mu-Yang Huang, Le-Le Zhang, Min-Xia Su, Xiuping Chen, Jin-Jian Lu
Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). In NSCLC patients, an EGFR mutation is likely to be correlated with high levels of expression of programmed death ligand-1 (PD-L1). Here, we showed that osimertinib decreased PD-L1 expression in human EGFR mutant NSCLC cells in vitro. Osimertinib (125 nmol/L) markedly suppressed PD-L1 mRNA expression in both NCI-H1975 and HCC827 cells...
September 7, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28880012/golph2-regulated-oncolytic-adenovirus-gd55-exerts-strong-killing-effect-on-human-prostate-cancer-stem-like-cells-in-vitro-and-in-vivo
#14
Chang Ying, Bo-Duan Xiao, Yun Qin, Bin-Rong Wang, Xin-Yuan Liu, Ru-Wei Wang, Ling Fang, Hui Yan, Xiu-Mei Zhou, Yi-Gang Wang
GOLPH2 (also called GP73) is a Golgi glycoprotein, which has been identified as a novel tumor marker upregulated in various cancers, including prostate cancer (PCa). GD55 is a novel GOLPH2-regulated oncolytic adenovirus that exhibits a strong killing effect on hepatoma cells. Here, we investigate the antitumor effect of GD55 on prostate cancer stem cell (CSC)-like cells in vitro and in vivo. Prostate CSC-like sphere cells were acquired and enriched by culturing DU145, LNCap or P3 prostate cancer cells in suspension...
September 7, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28858301/activation-of-aldehyde-dehydrogenase-2-slows-down-the-progression-of-atherosclerosis-via-attenuation-of-er-stress-and-apoptosis-in-smooth-muscle-cells
#15
Mei-Yan Yang, Ya-Bin Wang, Bo Han, Bo Yang, Yu-Wei Qiang, Yan Zhang, Zhao Wang, Xu Huang, Jie Liu, Yun-Dai Chen, Jun Ren, Feng Cao, Yong Xu
Aldehyde dehydrogenase 2 (ALDH2) is a key mitochondrial enzyme in the metabolism of aldehydes and may have beneficial cardiovascular effects for conditions such as cardiac hypertrophy, heart failure, myocardial I/R injury, reperfusion, arrhythmia, coronary heart disease and atherosclerosis. In this study we investigated the role of ALDH2 in the progression of atherosclerosis and the underlying mechanisms, with a focus on endoplasmic reticulum (ER) stress. A clinical study was performed in 248 patients with coronary heart disease...
August 31, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28858300/development-of-a-high-throughput-fluorescence-polarization-assay-for-the-discovery-of-ezh2-eed-interaction-inhibitors
#16
Mao-Rong Zhu, Dao-Hai Du, Jun-Chi Hu, Lian-Chun Li, Jing-Qiu Liu, Hong Ding, Xiang-Qian Kong, Hua-Liang Jiang, Kai-Xian Chen, Cheng Luo
Aberrant activity of enhancer of zeste homolog 2 (EZH2) is associated with a wide range of human cancers. The interaction of EZH2 with embryonic ectoderm development (EED) is required for EZH2's catalytic activity. Inhibition of the EZH2-EED complex thus represents a novel strategy for interfering with the oncogenic potentials of EZH2 by targeting both its catalytic and non-catalytic functions. To date, there have been no reported high-throughput screening (HTS) assays for inhibitors acting at the EZH2-EED interface...
August 31, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28858299/synthesis-and-in-vitro-biological-evaluation-of-thiosulfinate-derivatives-for-the-treatment-of-human-multidrug-resistant-breast-cancer
#17
Ariane Roseblade, Alison Ung, Mary Bebawy
Organosulfur compounds derived from Allium vegetables have long been recognized for various therapeutic effects, including anticancer activity. Allicin, one of the main biologically active components of garlic, shows promise as an anticancer agent; however, instability makes it unsuitable for clinical application. The aim of this study was to investigate the effect of stabilized allicin derivatives on human breast cancer cells in vitro. In this study, a total of 22 stabilized thiosulfinate derivatives were synthesized and screened for their in vitro antiproliferative activities against drug-sensitive (MCF-7) and multidrug-resistant (MCF-7/Dx) human adenocarcinoma breast cancer cells...
August 31, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28858298/crystal-structure-based-comparison-of-two-nampt-inhibitors
#18
Sai-Long Zhang, Tian-Ying Xu, Zhen-Lin Yang, Shuo Han, Qiang Zhao, Chao-Yu Miao
Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) is a novel strategy for cancer therapy, but only two inhibitors of NAMPT (FK866 and CHS828) have progressed into clinical trials. This study seeks to compare a novel potent NAMPT inhibitor, MS0, with a classical inhibitor FK866 in their biological activity and molecular binding mode, thereby contributing to future chemical optimization and a further understanding of the action mode of NAMPT inhibitors. The IC50 values of MS0 and FK866 in inhibition of recombinant human NAMPT activity were 9...
August 31, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28858297/yl-0919-a-dual-5-ht1a-partial-agonist-and-ssri-produces-antidepressant-and-anxiolytic-like-effects-in-rats-subjected-to-chronic-unpredictable-stress
#19
Yu-Hua Ran, Xiao-Xu Hu, Yu-Lu Wang, Nan Zhao, Li-Ming Zhang, Hua-Xia Liu, Yun-Feng Li
YL-0919 has been identified as a novel dual 5-HT1A partial agonist and serotonin reuptake inhibitor. In the current study, we demonstrated that YL-0919 produced prominent antidepressant-like and anxiolytic-like effects in a chronic unpredictable stress (CUS) rat model. Male SD rats were exposed to CUS for 5 weeks; YL-0919 (1.25 and 2.5 mg/kg) or a positive control fluoxetine (Flx, 10 mg/kg) was orally administered daily. YL-0919 or Flx treatment significantly increased the sucrose preference rate, the locomotor activity in an open field test (OFT), the latency to feed in a novelty-suppressed feeding test (NSFT), and both the percentage of time spent in the open arms and the number of entries into the open arms in an elevated plus-maze test...
August 31, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28858296/ccn3-suppresses-tgf-%C3%AE-1-induced-extracellular-matrix-accumulation-in-human-mesangial-cells-in-vitro
#20
Hai-Fei Liu, Hong Liu, Lin-Li Lv, Kun-Ling Ma, Yi Wen, Long Chen, Bi-Cheng Liu
Glomerular sclerosis is characterized by mesangial cell proliferation and progressive extracellular matrix (ECM) accumulation. CCN3 belongs to the CCN family of matrix proteins; increasing evidence suggests that CCN3 is an endogenous negative regulator of the ECM and fibrosis. However, the exact role of CCN3 in the accumulation of ECM remains unknown. The aim of the present study was to investigate the effects of CCN3 on TGF-β1-induced production of ECM in human mesangial cells (HMCs) in vitro. Treatment with TGF-β1 (0...
August 31, 2017: Acta Pharmacologica Sinica
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