CUDC-907 displays potent antitumor activity against human pancreatic adenocarcinoma in vitro and in vivo through inhibition of HDAC6 to downregulate c-Myc expression.
In this study, we investigated the effect of CUDC-907 on human pancreatic cancer cells in vitro and in vivo. Our results showed that CUDC-907 potently inhibited the proliferation of 9 pancreatic cancer cell lines in vitro with IC50 values ranging from 6.7 to 54.5 nM. Furthermore, we revealed the antitumor mechanism of CUDC-907 in Aspc-1, PANC-1, and Capan-1 pancreatic cancer cells: it suppressed the HDAC6 subunit, thus downregulating c-Myc protein levels, which was a mode of action distinct from the existing mechanisms. Consistently, the extraordinary antitumor activity of CUDC-907 accompanied by downregulation of c...
Source: Acta Pharmacologica Sinica - September 17, 2018 Category: Drugs & Pharmacology Authors: Fu XH, Zhang X, Yang H, Xu XW, Hu ZL, Yan J, Zheng XL, Wei RR, Zhang ZQ, Tang SR, Geng MY, Huang X Tags: Acta Pharmacol Sin Source Type: research

Selective dopamine D3 receptor antagonist YQA14 inhibits morphine-induced behavioral sensitization in wild type, but not in dopamine D3 receptor knockout mice.
In this study we investigated the effects of YQA14 on morphine-induced context-specific locomotor sensitization in mice. We showed that repeated injection of YQA14 (6.25-25 mg/kg every day ip) prior to morphine (10 mg/kg every day sc) not only inhibited the acquisition, but also significantly attenuated the expression of morphine-induced locomotor sensitization. Furthermore, in the expression phase, one single injection of YQA14 (6.25-25 mg/kg, ip) dose-dependently inhibited the expression of morphine-induced behavioral sensitization. Moreover, YQA14 inhibited the expression of morphine-induced behavio...
Source: Acta Pharmacologica Sinica - September 17, 2018 Category: Drugs & Pharmacology Authors: Lv Y, Hu RR, Jing M, Zhao TY, Wu N, Song R, Li J, Hu G Tags: Acta Pharmacol Sin Source Type: research

Selective dopamine D3 receptor antagonist YQA14 inhibits morphine-induced behavioral sensitization in wild type, but not in dopamine D3 receptor knockout mice
Selective dopamine D3 receptor antagonist YQA14 inhibits morphine-induced behavioral sensitization in wild type, but not in dopamine D3 receptor knockout mice, Published online: 17 September 2018; doi:10.1038/s41401-018-0153-0Selective dopamine D3 receptor antagonist YQA14 inhibits morphine-induced behavioral sensitization in wild type, but not in dopamine D3 receptor knockout mice (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - September 17, 2018 Category: Drugs & Pharmacology Authors: Yang Lv Rong-rong Hu Manyi Jing Tai-yun Zhao Ning Wu Rui Song Jin Li Gang Hu Source Type: research

CUDC-907 displays potent antitumor activity against human pancreatic adenocarcinoma in vitro and in vivo through inhibition of HDAC6 to downregulate c-Myc expression
CUDC-907 displays potent antitumor activity against human pancreatic adenocarcinoma in vitro and in vivo through inhibition of HDAC6 to downregulate c-Myc expression, Published online: 17 September 2018; doi:10.1038/s41401-018-0108-5CUDC-907 displays potent antitumor activity against human pancreatic adenocarcinoma in vitro and in vivo through inhibition of HDAC6 to downregulate c-Myc expression (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - September 17, 2018 Category: Drugs & Pharmacology Authors: Xu-hong Fu Xiong Zhang Hong Yang Xiao-wei Xu Zong-long Hu Juan Yan Xing-ling Zheng Rong-rui Wei Zhu-qing Zhang Shi-rui Tang Mei-yu Geng Xun Huang Source Type: research

Is the combinational administration of doxorubicin and glutathione a reasonable proposal?
Abstract The combinational administration of antioxidants and chemotherapeutic agents during conventional cancer treatment is among one of the most controversial areas in oncology. Although the data on the combinational usage of doxorubicin (DOX) and glutathione (GSH) agents have been explored for over 20 years, the duration, administration route, and authentic rationality have not yet been fully understood yet. In the current study, we systematically investigated the pharmacokinetics (PK) and pharmacodynamics (PD) with both in vivo and in vitro models to elucidate the influence of GSH on the toxicity and efficacy...
Source: Acta Pharmacologica Sinica - September 14, 2018 Category: Drugs & Pharmacology Authors: Shen BY, Chen C, Xu YF, Shen JJ, Guo HM, Li HF, Li XN, Kang D, Shao YH, Zhu ZP, Yin XX, Xie L, Wang GJ, Liang Y Tags: Acta Pharmacol Sin Source Type: research

Hispidulin induces ER stress-mediated apoptosis in human hepatocellular carcinoma cells in vitro and in vivo by activating AMPK signaling pathway.
This study provides new insights into the anti-tumor activity of hispidulin in HCC. PMID: 30218072 [PubMed - as supplied by publisher] (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - September 14, 2018 Category: Drugs & Pharmacology Authors: Han M, Gao H, Xie J, Yuan YP, Yuan Q, Gao MQ, Liu KL, Chen XH, Han YT, Han ZW Tags: Acta Pharmacol Sin Source Type: research

Is the combinational administration of doxorubicin and glutathione a reasonable proposal?
Is the combinational administration of doxorubicin and glutathione a reasonable proposal?, Published online: 14 September 2018; doi:10.1038/s41401-018-0158-8Is the combinational administration of doxorubicin and glutathione a reasonable proposal? (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - September 14, 2018 Category: Drugs & Pharmacology Authors: Bo-yu Shen Chong Chen Yang-fan Xu Jia-jia Shen Hui-min Guo Hao-feng Li Xi-nuo Li Dian Kang Yu-hao Shao Zhang-pei Zhu Xiao-xi Yin Lin Xie Guang-ji Wang Yan Liang Source Type: research

Hispidulin induces ER stress-mediated apoptosis in human hepatocellular carcinoma cells in vitro and in vivo by activating AMPK signaling pathway
Hispidulin induces ER stress-mediated apoptosis in human hepatocellular carcinoma cells in vitro and in vivo by activating AMPK signaling pathway, Published online: 14 September 2018; doi:10.1038/s41401-018-0159-7Hispidulin induces ER stress-mediated apoptosis in human hepatocellular carcinoma cells in vitro and in vivo by activating AMPK signaling pathway (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - September 14, 2018 Category: Drugs & Pharmacology Authors: Mei Han Hui Gao Jing Xie Yin-ping Yuan Quan Yuan Ming-quan Gao Kai-li Liu Xue-hong Chen Yan-tao Han Zhi-wu Han Source Type: research

Identification of novel mouse and rat CB1R isoforms and in silico modeling of human CB1R for peripheral cannabinoid therapeutics.
In this study, we found no evidence of peripherally enriched rodent CB1 isoforms; however, some mCB1R isoforms are absent in peripheral tissues. We show that the mouse Cnr1 gene contains six exons that are transcribed from a single promoter. We found that mCB1A is a spliced variant of extended exon 1 and protein-coding exon 6; mCB1B is a novel spliced variant containing unspliced exon 1, intron 1, and exon 2, which is then spliced to exon 6; and mCB1C is a spliced variant including all 6 exons. Using RNAscope in situ hybridization, we show that the isoforms mCB1A and mCB1B are expressed at a cellular level and colocalized ...
Source: Acta Pharmacologica Sinica - September 10, 2018 Category: Drugs & Pharmacology Authors: Liu QR, Huang NS, Qu H, O'Connell JF, Gonzalez-Mariscal I, Santa-Cruz-Calvo S, Doyle ME, Xi ZX, Wang Y, Onaivi ES, Egan JM Tags: Acta Pharmacol Sin Source Type: research

Heterogeneity of cannabinoid ligand-induced modulations in intracellular Ca2+ signals of mouse pancreatic acinar cells in vitro.
In conclusion, CB2R agonists play critical roles in modulating Ca2+ signals in mouse pancreatic acinar cells, while other cannabinoid ligands modulate Ca2+ oscillations in a heterogeneous manner through a CB receptor or non-CB-receptor mechanism. PMID: 30202013 [PubMed - as supplied by publisher] (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - September 10, 2018 Category: Drugs & Pharmacology Authors: Xia KK, Shen JX, Huang ZB, Song HM, Gao M, Chen DJ, Zhang SJ, Wu J Tags: Acta Pharmacol Sin Source Type: research

Computational systems pharmacology analysis of cannabidiol: a combination of chemogenomics-knowledgebase network analysis and integrated in silico modeling and simulation.
Abstract With treatment benefits in both the central nervous system and the peripheral system, the medical use of cannabidiol (CBD) has gained increasing popularity. Given that the therapeutic mechanisms of CBD are still vague, the systematic identification of its potential targets, signaling pathways, and their associations with corresponding diseases is of great interest for researchers. In the present work, chemogenomics-knowledgebase systems pharmacology analysis was applied for systematic network studies to generate CBD-target, target-pathway, and target-disease networks by combining both the results from the...
Source: Acta Pharmacologica Sinica - September 10, 2018 Category: Drugs & Pharmacology Authors: Bian YM, He XB, Jing YK, Wang LR, Wang JM, Xie XQ Tags: Acta Pharmacol Sin Source Type: research

Identification of novel mouse and rat CB1R isoforms and in silico modeling of human CB1R for peripheral cannabinoid therapeutics
Identification of novel mouse and rat CB1R isoforms and in silico modeling of human CB1R for peripheral cannabinoid therapeutics, Published online: 10 September 2018; doi:10.1038/s41401-018-0152-1Identification of novel mouse and rat CB1R isoforms and in silico modeling of human CB1R for peripheral cannabinoid therapeutics (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - September 10, 2018 Category: Drugs & Pharmacology Authors: Qing-Rong Liu Nicholas S. Huang Hong Qu Jennifer F. O ’Connell Isabel Gonzalez-Mariscal Sara Santa-Cruz-Calvo Maire E. Doyle Zheng-Xiong. Xi Yun Wang Emmanuel. S. Onaivi Josephine M. Egan Source Type: research

Heterogeneity of cannabinoid ligand-induced modulations in intracellular Ca2+ signals of mouse pancreatic acinar cells in vitro
Heterogeneity of cannabinoid ligand-induced modulations in intracellular Ca2+ signals of mouse pancreatic acinar cells in vitro, Published online: 10 September 2018; doi:10.1038/s41401-018-0074-yHeterogeneity of cannabinoid ligand-induced modulations in intracellular Ca2+ signals of mouse pancreatic acinar cells in vitro (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - September 10, 2018 Category: Drugs & Pharmacology Authors: Kun-kun Xia Jian-xin Shen Ze-bing Huang Hui-min Song Ming Gao De-jie Chen Shui-jun Zhang Jie Wu Source Type: research

Computational systems pharmacology analysis of cannabidiol: a combination of chemogenomics-knowledgebase network analysis and integrated in silico modeling and simulation
Computational systems pharmacology analysis of cannabidiol: a combination of chemogenomics-knowledgebase network analysis and integrated in silico modeling and simulation, Published online: 10 September 2018; doi:10.1038/s41401-018-0071-1Computational systems pharmacology analysis of cannabidiol: a combination of chemogenomics-knowledgebase network analysis and integrated in silico modeling and simulation (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - September 10, 2018 Category: Drugs & Pharmacology Authors: Yue-min Bian Xi-bing He Yan-kang Jing Li-rong Wang Jun-mei Wang Xiang-Qun Xie Source Type: research

The oncoprotein HBXIP promotes human breast cancer growth through down-regulating p53 via miR-18b/MDM2 and pAKT/MDM2 pathways.
In conclusion, oncoprotein HBXIP suppresses miR-18b to elevate MDM2 and activates pAKT to phosphorylate MDM2 for enhancing the interaction between MDM2 and p53, leading to p53 degradation in promotion of breast cancer growth. Our findings shed light on a novel mechanism of p53 down-regulation during the development of breast cancer. PMID: 30181579 [PubMed - as supplied by publisher] (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - September 4, 2018 Category: Drugs & Pharmacology Authors: Li H, Wang Z, Jiang M, Fang RP, Shi H, Shen Y, Cai XL, Liu Q, Ye K, Fan SJ, Zhang WY, Ye LH Tags: Acta Pharmacol Sin Source Type: research

The oncoprotein HBXIP promotes human breast cancer growth through down-regulating p53 via miR-18b/MDM2 and pAKT/MDM2 pathways
The oncoprotein HBXIP promotes human breast cancer growth through down-regulating p53 via miR-18b/MDM2 and pAKT/MDM2 pathways, Published online: 04 September 2018; doi:10.1038/s41401-018-0034-6The oncoprotein HBXIP promotes human breast cancer growth through down-regulating p53 via miR-18b/MDM2 and pAKT/MDM2 pathways (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - September 4, 2018 Category: Drugs & Pharmacology Authors: Hang Li Zhen Wang Mian Jiang Run-ping Fang Hui Shi Yu Shen Xiao-li Cai Qian Liu Kai Ye Sai-jun Fan Wei-ying Zhang Li-hong Ye Source Type: research

Acetyl-11-keto-β-boswellic acid suppresses docetaxel-resistant prostate cancer cells in vitro and in vivo by blocking Akt and Stat3 signaling, thus suppressing chemoresistant stem cell-like properties
Acetyl-11-keto-β-boswellic acid suppresses docetaxel-resistant prostate cancer cells in vitro and in vivo by blocking Akt and Stat3 signaling, thus suppressing chemoresistant stem cell-like propertiesAcetyl-11-keto-β-boswellic acid suppresses docetaxel-resistant prostate cancer cells in vitro and in vivo by blocking Akt and Stat3 signaling, thus suppressing chemoresistant stem cell-like properties, Published online: 31 August 2018; doi:10.1038/s41401-018-0157-9Acetyl-11-keto-β-boswellic acid suppresses docetaxel-resistant prostate cancer cells in vitro and in vivo by blocking Akt and Stat3 signaling, thus su...
Source: Acta Pharmacologica Sinica - August 31, 2018 Category: Drugs & Pharmacology Authors: Yong-qing Liu Shi-kang Wang Qing-qing Xu Hui-qing Yuan Yan-xia Guo Qian Wang Feng Kong Zhao-min Lin De-qing Sun Rong-mei Wang Hong-xiang Lou Source Type: research

Fluoxetine induces lipid metabolism abnormalities by acting on the liver in patients and mice with depression.
Abstract Depressive disorders are frequently managed with long-term use of antidepressant medication. Fluoxetine (FLX) is the first selective serotonin reuptake inhibitor to be widely available for the treatment of depression. The present study focuses on the effects and mechanisms of the lipid metabolism abnormalities caused by FLX in patients and in a mouse model of depression. Depression severity was assessed by the Hamilton Depression Scale (HAMD). Triglyceride (TG), cholesterol (TC) and low-density lipoprotein (LDL) serum levels were assessed in 28 patients with depression, aged 31.2±3.3 years, treated...
Source: Acta Pharmacologica Sinica - August 30, 2018 Category: Drugs & Pharmacology Authors: Pan SJ, Tan YL, Yao SW, Xin Y, Yang X, Liu J, Xiong J Tags: Acta Pharmacol Sin Source Type: research

SND p102 promotes extracellular matrix accumulation and cell proliferation in rat glomerular mesangial cells via the AT1R/ERK/Smad3 pathway.
In this study, we further examined the roles of SND p102 in diabetic nephropathy (DN)-induced glomerulosclerosis. Rats were injected with STZ (50 mg/kg, ip) to induce diabetes. MCs or isolated glomeruli were cultured in normal glucose (NG, 5.5 mmol/L)- or high glucose (HG, 25 mmol/L)-containing DMEM. We found that SND p102 expression was significantly increased in the diabetic kidneys, as well as in HG-treated isolated glomeruli and MCs. In addition, HG treatment induced significant fibrotic changes in MCs evidenced by enhanced protein expression of TGF-β, fbronectin and collagen IV, and significantly increased the pr...
Source: Acta Pharmacologica Sinica - August 30, 2018 Category: Drugs & Pharmacology Authors: Xu JL, Gan XX, Ni J, Shao DC, Shen Y, Miao NJ, Xu D, Zhou L, Zhang W, Lu LM Tags: Acta Pharmacol Sin Source Type: research

Endocannabinoid signaling in psychiatric disorders: a review of positron emission tomography studies
Endocannabinoid signaling in psychiatric disorders: a review of positron emission tomography studies, Published online: 30 August 2018; doi:10.1038/s41401-018-0081-zEndocannabinoid signaling in psychiatric disorders: a review of positron emission tomography studies (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - August 30, 2018 Category: Drugs & Pharmacology Authors: Matthew E. Sloan Caroline W. Grant Joshua L. Gowin Vijay A. Ramchandani Bernard Le Foll Source Type: research

A pharmacodynamic model of respiratory rate and end-tidal carbon dioxide values during anesthesia in children
A pharmacodynamic model of respiratory rate and end-tidal carbon dioxide values during anesthesia in children, Published online: 30 August 2018; doi:10.1038/s41401-018-0156-xA pharmacodynamic model of respiratory rate and end-tidal carbon dioxide values during anesthesia in children (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - August 30, 2018 Category: Drugs & Pharmacology Authors: Ji-Hyun Lee Pyo-Yoon Kang Young-Eun Jang Eun-Hee Kim Jin-Tae Kim Hee-Soo Kim Source Type: research

HOTAIR lncRNA SNPs rs920778 and rs1899663 are associated with smoking, male gender, and squamous cell carcinoma in a Chinese lung cancer population.
Abstract The abnormal expression of the long noncoding RNA (lncRNA) HOX transcript intergenic antisense RNA (HOTAIR) plays an important role in the development of various cancers; however, single nucleotide polymorphisms (SNPs) in HOTAIR and their association with primary lung cancer susceptibility have not yet been reported. Here, we performed a case-control study including 262 primary lung cancer patients and 451 cancer-free control individuals to investigate the association between four haplotype-tagging SNPs (rs920778, rs12826786, rs4759314, and rs1899663) in the HOTAIR lncRNA and the risk of developing primar...
Source: Acta Pharmacologica Sinica - August 28, 2018 Category: Drugs & Pharmacology Authors: Wang C, Li Y, Li YW, Zhang HB, Gong H, Yuan Y, Li WT, Liu HY, Chen J Tags: Acta Pharmacol Sin Source Type: research

HOTAIR lncRNA SNPs rs920778 and rs1899663 are associated with smoking, male gender, and squamous cell carcinoma in a Chinese lung cancer population
HOTAIR lncRNA SNPs rs920778 and rs1899663 are associated with smoking, male gender, and squamous cell carcinoma in a Chinese lung cancer population, Published online: 28 August 2018; doi:10.1038/s41401-018-0083-xHOTAIR lncRNA SNPs rs920778 and rs1899663 are associated with smoking, male gender, and squamous cell carcinoma in a Chinese lung cancer population (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - August 28, 2018 Category: Drugs & Pharmacology Authors: Cong Wang Ying Li Yong-wen Li Hong-bing Zhang Hao Gong Yin Yuan Wei-ting Li Hong-yu Liu Jun Chen Source Type: research

Overexpression of steroid receptor coactivators alleviates hyperglycemia-induced endothelial cell injury in rats through activating the PI3K/Akt pathway.
In conclusion, hyperglycemia decreased SRC-1 and SRC-3 expression levels in rat aortic endothelial cells. SRC-1 and SRC-3 overexpression might protect against endothelial injury via inhibition of oxidative stress and activation of PI3K/Akt pathway. PMID: 30089865 [PubMed - as supplied by publisher] (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - August 8, 2018 Category: Drugs & Pharmacology Authors: Quan XJ, Liang CL, Sun MZ, Zhang L, Li XL Tags: Acta Pharmacol Sin Source Type: research

Overexpression of steroid receptor coactivators alleviates hyperglycemia-induced endothelial cell injury in rats through activating the PI3K/Akt pathway
Overexpression of steroid receptor coactivators alleviates hyperglycemia-induced endothelial cell injury in rats through activating the PI3K/Akt pathway, Published online: 08 August 2018; doi:10.1038/s41401-018-0109-4Overexpression of steroid receptor coactivators alleviates hyperglycemia-induced endothelial cell injury in rats through activating the PI3K/Akt pathway (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - August 8, 2018 Category: Drugs & Pharmacology Authors: Xiao-juan Quan Chun-lian Liang Ming-zhu Sun Lin Zhang Xiu-li Li Source Type: research

18 β-Glycyrrhetinic acid protects against alpha-naphthylisothiocyanate-induced cholestasis through activation of the Sirt1/FXR signaling pathway.
18β-Glycyrrhetinic acid protects against alpha-naphthylisothiocyanate-induced cholestasis through activation of the Sirt1/FXR signaling pathway. Acta Pharmacol Sin. 2018 Jul 30;: Authors: Wu SY, Cui SC, Wang L, Zhang YT, Yan XX, Lu HL, Xing GZ, Ren J, Gong LK Abstract Cholestasis is a common feature of liver injury, which manifests as bile acid excretion and/or enterohepatic circulation disorders. However, very few effective therapies exist for cholestasis. Recently, 18β-Glycyrrhetinic acid (18b-GA), a major metabolic component of glycyrrhizin, which is the main ingredient of licorice, was r...
Source: Acta Pharmacologica Sinica - July 30, 2018 Category: Drugs & Pharmacology Authors: Wu SY, Cui SC, Wang L, Zhang YT, Yan XX, Lu HL, Xing GZ, Ren J, Gong LK Tags: Acta Pharmacol Sin Source Type: research

18β-Glycyrrhetinic acid protects against alpha-naphthylisothiocyanate-induced cholestasis through activation of the Sirt1/FXR signaling pathway
18β-Glycyrrhetinic acid protects against alpha-naphthylisothiocyanate-induced cholestasis through activation of the Sirt1/FXR signaling pathway18β-Glycyrrhetinic acid protects against alpha-naphthylisothiocyanate-induced cholestasis through activation of the Sirt1/FXR signaling pathway, Published online: 30 July 2018; doi:10.1038/s41401-018-0110-y18β-Glycyrrhetinic acid protects against alpha-naphthylisothiocyanate-induced cholestasis through activation of the Sirt1/FXR signaling pathway (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 30, 2018 Category: Drugs & Pharmacology Authors: Shou-yan Wu Shi-chao Cui Le Wang Yi-ting Zhang Xiao-xia Yan Heng-lei Lu Guo-zhen Xing Jin Ren Li-kun Gong Source Type: research

Human pharmacokinetics of ginkgo terpene lactones and impact of carboxylation in blood on their platelet-activating factor antagonistic activity.
Abstract Terpene lactones are a class of bioactive constituents of standardized preparations of Ginkgo biloba leaf extract, extensively used as add-on therapies in patients with ischemic cardiovascular and cerebrovascular diseases. This investigation evaluated human pharmacokinetics of ginkgo terpene lactones and impact of their carboxylation in blood. Human subjects received oral YinXing-TongZhi tablet or intravenous ShuXueNing, two standardized ginkgo preparations. Their plasma protein-binding and platelet-activating factor antagonistic activity were assessed in vitro. Their carboxylation was assessed in phospha...
Source: Acta Pharmacologica Sinica - July 27, 2018 Category: Drugs & Pharmacology Authors: Liu XW, Yang JL, Niu W, Jia WW, Olaleye OE, Wen Q, Duan XN, Huang YH, Wang FQ, Du FF, Zhong CC, Li YF, Xu F, Gao Q, Li L, Li C Tags: Acta Pharmacol Sin Source Type: research

Human pharmacokinetics of ginkgo terpene lactones and impact of carboxylation in blood on their platelet-activating factor antagonistic activity
Human pharmacokinetics of ginkgo terpene lactones and impact of carboxylation in blood on their platelet-activating factor antagonistic activity, Published online: 27 July 2018; doi:10.1038/s41401-018-0086-7Human pharmacokinetics of ginkgo terpene lactones and impact of carboxylation in blood on their platelet-activating factor antagonistic activity (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 27, 2018 Category: Drugs & Pharmacology Authors: Xin-wei Liu Jun-ling Yang Wei Niu Wei-wei Jia Olajide E. Olaleye Qi Wen Xiao-na Duan Y ü-hong Huang Feng-qing Wang Fei-fei Du Chen-chun Zhong Yan-fen Li Fang Xu Qi Gao Li Li Chuan Li Source Type: research

Brain activity of anandamide: a rewarding bliss?
Abstract Anandamide is a lipid mediator that acts as an endogenous ligand of CB1 receptors. These receptors are also the primary molecular target responsible for the pharmacological effects of Δ9-tetrahydrocannabinol, the psychoactive ingredient in Cannabis sativa. Several studies demonstrate that anandamide exerts an overall modulatory effect on the brain reward circuitry. Several reports suggest its involvement in the addiction-producing actions of other abused drugs, and it can also act as a behavioral reinforcer in animal models of drug abuse. Importantly, all these effects of anandamide appear to be pot...
Source: Acta Pharmacologica Sinica - July 26, 2018 Category: Drugs & Pharmacology Authors: Scherma M, Masia P, Satta V, Fratta W, Fadda P, Tanda G Tags: Acta Pharmacol Sin Source Type: research

Emerging roles of sphingosylphosphorylcholine in modulating cardiovascular functions and diseases.
Abstract Sphingosylphosphorylcholine (SPC) is a bioactive sphingolipid in blood plasma that is metabolized from the hydrolysis of the membrane sphingolipid. SPC maintains low levels in the circulation under normal conditions, which makes studying its origin and action difficult. In recent years, however, it has been revealed that SPC may act as a first messenger through G protein-coupled receptors (S1P1-5, GPR12) or membrane lipid rafts, or as a second messenger mediating intracellular Ca2+ release in diverse human organ systems. SPC is a constituent of lipoproteins, and the activation of platelets promotes the re...
Source: Acta Pharmacologica Sinica - July 26, 2018 Category: Drugs & Pharmacology Authors: Ge D, Yue HW, Liu HH, Zhao J Tags: Acta Pharmacol Sin Source Type: research

Emerging roles of sphingosylphosphorylcholine in modulating cardiovascular functions and diseases
Emerging roles of sphingosylphosphorylcholine in modulating cardiovascular functions and diseases, Published online: 26 July 2018; doi:10.1038/s41401-018-0036-4Emerging roles of sphingosylphosphorylcholine in modulating cardiovascular functions and diseases (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 26, 2018 Category: Drugs & Pharmacology Authors: Di Ge Hong-wei Yue Hong-hong Liu Jing Zhao Source Type: research

Brain activity of anandamide: a rewarding bliss?
Brain activity of anandamide: a rewarding bliss?, Published online: 26 July 2018; doi:10.1038/s41401-018-0075-xBrain activity of anandamide: a rewarding bliss? (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 26, 2018 Category: Drugs & Pharmacology Authors: Maria Scherma Paolo Masia Valentina Satta Walter Fratta Paola Fadda Gianluigi Tanda Source Type: research

Dysregulation of miR-135a-5p promotes the development of rat pulmonary arterial hypertension in vivo and in vitro.
In this study, we established rat primary PAH models using monocrotaline (MCT) injection or hypoxic exposure, then investigated the expression patterns of seven miRNAs associated with multiple pathogenic pathways central to pulmonary hypertension, and further explored the roles and the possible mechanisms of miR-135a during the development of PAH. In the rat primary PAH models, we observed that the expression of miR-135a-5p in lungs was drastically decreased at the initial stage of PAH development after MCT administration or hypoxic exposure, but it increased by 12-fold or 10-fold at the later stage. In vitro study in PASM...
Source: Acta Pharmacologica Sinica - July 23, 2018 Category: Drugs & Pharmacology Authors: Liu HM, Jia Y, Zhang YX, Yan J, Liao N, Li XH, Tang Y Tags: Acta Pharmacol Sin Source Type: research

Identification, structure modification, and characterization of potential small-molecule SGK3 inhibitors with novel scaffolds.
Abstract The serum and glucocorticoid-regulated kinase (SGK) family has been implicated in the regulation of many cellular processes downstream of the PI3K pathway. It plays a crucial role in PI3K-mediated tumorigenesis, making it a potential therapeutic target for cancer. SGK family consists of three isoforms (SGK1, SGK2, and SGK3), which have high sequence homology in the kinase domain and similar substrate specificity with the AKT family. In order to identify novel compounds capable of inhibiting SGK3 activity, a high-throughput screening campaign against 50,400 small molecules was conducted using a fluorescenc...
Source: Acta Pharmacologica Sinica - July 23, 2018 Category: Drugs & Pharmacology Authors: Gong GQ, Wang K, Dai XC, Zhou Y, Basnet R, Chen Y, Yang DH, Lee WJ, Buchanan CM, Flanagan JU, Shepherd PR, Chen Y, Wang MW Tags: Acta Pharmacol Sin Source Type: research

Identification, structure modification, and characterization of potential small-molecule SGK3 inhibitors with novel scaffolds
Identification, structure modification, and characterization of potential small-molecule SGK3 inhibitors with novel scaffolds, Published online: 23 July 2018; doi:10.1038/s41401-018-0087-6Identification, structure modification, and characterization of potential small-molecule SGK3 inhibitors with novel scaffolds (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 23, 2018 Category: Drugs & Pharmacology Authors: Grace Qun Gong Ke Wang Xin-Chuan Dai Yan Zhou Rajesh Basnet Yi Chen De-Hua Yang Woo-Jeong Lee Christina Maree Buchanan Jack Urquhart Flanagan Peter Robin Shepherd Ying Chen Ming-Wei Wang Source Type: research

Dysregulation of miR-135a-5p promotes the development of rat pulmonary arterial hypertension in vivo and in vitro
Dysregulation of miR-135a-5p promotes the development of rat pulmonary arterial hypertension in vivo and in vitro, Published online: 23 July 2018; doi:10.1038/s41401-018-0076-9Dysregulation of miR-135a-5p promotes the development of rat pulmonary arterial hypertension in vivo and in vitro (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 23, 2018 Category: Drugs & Pharmacology Authors: Hong-mei Liu Yi Jia Ying-xian Zhang Jun Yan Ning Liao Xiao-hui Li Yuan Tang Source Type: research

PARP1 interacts with HMGB1 and promotes its nuclear export in pathological myocardial hypertrophy.
Abstract High-mobility group box 1 (HMGB1) exhibits various functions according to its subcellular location, which is finely conditioned by diverse post-translational modifications, such as acetylation. The nuclear HMGB1 may prevent from cardiac hypertrophy, whereas its exogenous protein is proven to induce hypertrophic response. This present study sought to investigate the regulatory relationships between poly(ADP-ribose) polymerase 1 (PARP1) and HMGB1 in the process of pathological myocardial hypertrophy. Primary-cultured neonatal rat cardiomyocytes (NRCMs) were respectively incubated with three cardiac hypertro...
Source: Acta Pharmacologica Sinica - July 20, 2018 Category: Drugs & Pharmacology Authors: Li Q, Li ZM, Sun SY, Wang LP, Wang PX, Guo Z, Yang HW, Ye JT, Lu J, Liu PQ Tags: Acta Pharmacol Sin Source Type: research

Astragaloside IV attenuates myocardial ischemia/reperfusion injury in rats via inhibition of calcium-sensing receptor-mediated apoptotic signaling pathways.
In this study we investigated the molecular mechanisms by which AsIV attenuated the myocardial ischemia reperfusion (MI/R)-induced injury in vitro and in vivo by focusing on calcium-sensing receptor (CaSR) and extracellular signal-regulated kinase 1/2 (ERK1/2). Rat neonatal cardiac myocytes were subjected to a hypoxia/reoxygenation (H/R) procedure in vitro, which significantly decreased the cell viability, increased lactate dehydrogenase (LDH) release, induced cardiomyocyte apoptosis, and increased [Ca2+]i. H/R also increased the expression of CaSR and decreased ERK1/2 phosphorylation levels in H/R-exposed myocytes. Pretre...
Source: Acta Pharmacologica Sinica - July 20, 2018 Category: Drugs & Pharmacology Authors: Yin B, Hou XW, Lu ML Tags: Acta Pharmacol Sin Source Type: research

PARP1 interacts with HMGB1 and promotes its nuclear export in pathological myocardial hypertrophy
PARP1 interacts with HMGB1 and promotes its nuclear export in pathological myocardial hypertrophy, Published online: 20 July 2018; doi:10.1038/s41401-018-0044-4PARP1 interacts with HMGB1 and promotes its nuclear export in pathological myocardial hypertrophy (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 20, 2018 Category: Drugs & Pharmacology Authors: Qian LI Zhuo-ming LI Shu-ya SUN Lu-ping WANG Pan-xia WANG Zhen GUO Han-wei YANG Jian-tao YE Jing LU Pei-qing LIU Source Type: research

Astragaloside IV attenuates myocardial ischemia/reperfusion injury in rats via inhibition of calcium-sensing receptor-mediated apoptotic signaling pathways
Astragaloside IV attenuates myocardial ischemia/reperfusion injury in rats via inhibition of calcium-sensing receptor-mediated apoptotic signaling pathways, Published online: 20 July 2018; doi:10.1038/s41401-018-0082-yAstragaloside IV attenuates myocardial ischemia/reperfusion injury in rats via inhibition of calcium-sensing receptor-mediated apoptotic signaling pathways (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 20, 2018 Category: Drugs & Pharmacology Authors: Bo Yin Xu-wei Hou Mei-li Lu Source Type: research

Cannabidiol does not display drug abuse potential in mice behavior.
In this study, the behavioral profile of CBD as a potential drug of abuse was evaluated in C57BL/6J mice. Reinforcing properties of CBD (15, 30, and 60 mg/kg; i.p.) were assessed using the conditioned place preference (CPP) paradigm. Spontaneous withdrawal symptoms and motor activity in the open field were examined 12 h after the last CBD administration (30 mg/kg/12 h, i.p., 6 days). CBD plasma concentrations were measured at 2, 4, 8, 12, and 24 h after the administration of CBD (30 mg/kg, i.p.). Furthermore, an oral CBD self-administration paradigm (50 mg/kg; CBD water-solu...
Source: Acta Pharmacologica Sinica - July 18, 2018 Category: Drugs & Pharmacology Authors: Viudez-Martínez A, García-Gutiérrez MS, Medrano-Relinque J, Navarrón CM, Navarrete F, Manzanares J Tags: Acta Pharmacol Sin Source Type: research

Activation of SIRT1 ameliorates LPS-induced lung injury in mice via decreasing endothelial tight junction permeability.
In conclusion, SIRT1 ameliorates LPS-induced lung injury via decreasing endothelial tight junction permeability, possibly via RhoA/ROCK signaling pathway. This finding may contribute to the development of new therapeutic approaches for lung injury. PMID: 30022154 [PubMed - as supplied by publisher] (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 18, 2018 Category: Drugs & Pharmacology Authors: Fu C, Hao S, Xu X, Zhou J, Liu Z, Lu H, Wang L, Jin W, Li S Tags: Acta Pharmacol Sin Source Type: research

Cannabidiol does not display drug abuse potential in mice behavior
Cannabidiol does not display drug abuse potential in mice behavior, Published online: 18 July 2018; doi:10.1038/s41401-018-0032-8Cannabidiol does not display drug abuse potential in mice behavior (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 18, 2018 Category: Drugs & Pharmacology Authors: Adri án Viudez-Martínez Mar ía S. García-Gutiérrez Juan Medrano-Relinque Carmen M. Navarr ón Francisco Navarrete Jorge Manzanares Source Type: research

Activation of SIRT1 ameliorates LPS-induced lung injury in mice via decreasing endothelial tight junction permeability
Activation of SIRT1 ameliorates LPS-induced lung injury in mice via decreasing endothelial tight junction permeability, Published online: 18 July 2018; doi:10.1038/s41401-018-0045-3Activation of SIRT1 ameliorates LPS-induced lung injury in mice via decreasing endothelial tight junction permeability (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 18, 2018 Category: Drugs & Pharmacology Authors: Cuiping Fu Shengyu Hao Xiaobo Xu Jian Zhou Zilong Liu Huan Lu Limin Wang Weizhong Jin Shanqun Li Source Type: research

CircRNAFisher: a systematic computational approach for de novo circular RNA identification.
Abstract Circular RNAs (circRNAs) are emerging species of mRNA splicing products with largely unknown functions. Although several computational pipelines for circRNA identification have been developed, these methods strictly rely on uniquely mapped reads overlapping back-splice junctions (BSJs) and lack approaches to model the statistical significance of the identified circRNAs. Here, we reported a systematic computational approach to identify circRNAs by simultaneously utilizing BSJ overlapping reads and discordant BSJ spanning reads to identify circRNAs. Moreover, we developed a novel procedure to estimate the P...
Source: Acta Pharmacologica Sinica - July 16, 2018 Category: Drugs & Pharmacology Authors: Jia GY, Wang DL, Xue MZ, Liu YW, Pei YC, Yang YQ, Xu JM, Liang YC, Wang P Tags: Acta Pharmacol Sin Source Type: research

EGFR-targeting, β-defensin-tailored fusion protein exhibits high therapeutic efficacy against EGFR-expressed human carcinoma via mitochondria-mediated apoptosis.
In this study, a novel recombinant β-defensin that targets the epidermal growth factor receptor (EGFR) was designed and prepared. The EGFR-targeting β-defensin consists of an EGF-derived oligopeptide (Ec), a β-defensin-1 peptide (hBD1) and a lidamycin-derived apoprotein (LDP), which serves as the "scaffold" for the fusion protein (Ec-LDP-hBD1). Ec-LDP-hBD1 effectively bound to EGFR highly expressed human epidermoid carcinoma A431 cells. The cytotoxicity of Ec-LDP-hBD1 to EGFR highly expressed A431 cells was more potent than that to EGFR low-expressed human lung carcinoma A549 and H460 cells (the IC...
Source: Acta Pharmacologica Sinica - July 16, 2018 Category: Drugs & Pharmacology Authors: Liu WJ, Liu XJ, Xu J, Li L, Li Y, Zhang SH, Wang JL, Miao QF, Zhen YS Tags: Acta Pharmacol Sin Source Type: research

Activation of natural killer T cells contributes to triptolide-induced liver injury in mice.
Abstract Triptolide (TP) is the main active ingredient of Tripterygium wilfordii Hook.f, which has attracted great interest due to its promising efficacy for autoimmune diseases and tumors. However, severe adverse reactions, especially hepatotoxicity, have restricted its approval in the market. In the present study we explored the role of hepatic natural killer T (NKT) cells in the pathogenesis of TP-induced liver injury in mice. TP (600 μg/kg/day, i.g.) was administered to female mice for 1, 3, or 5 days. We found that administration of TP dose-dependently induced hepatotoxicity, evidenced by the body w...
Source: Acta Pharmacologica Sinica - July 16, 2018 Category: Drugs & Pharmacology Authors: Wang XZ, Xue RF, Zhang SY, Zheng YT, Zhang LY, Jiang ZZ Tags: Acta Pharmacol Sin Source Type: research

Isoalantolactone suppresses LPS-induced inflammation by inhibiting TRAF6 ubiquitination and alleviates acute lung injury.
In this study we investigated the therapeutic effects of IAL on acute lung injury (ALI) and elucidated the mechanisms underlying its anti-inflammation potential in vitro and in vivo. Treatment with lipopolysaccharide (LPS, 100 ng/mL) drastically stimulated production of inflammatory mediators such as NO, TNF-α, IL-1β, and IL-6 in mouse bone marrow-derived macrophages (BMDMs), which was dose-dependently suppressed by pretreatment with IAL (2.5, 5, 10, 20 μM). We further revealed that IAL suppressed LPS-induced NF-κB, ERK, and Akt activation. Moreover, the downregulation of non-degradable K6...
Source: Acta Pharmacologica Sinica - July 16, 2018 Category: Drugs & Pharmacology Authors: Ding YH, Song YD, Wu YX, He HQ, Yu TH, Hu YD, Zhang DP, Jiang HC, Yu KK, Li XZ, Sun L, Qian F Tags: Acta Pharmacol Sin Source Type: research

EGFR-targeting, β-defensin-tailored fusion protein exhibits high therapeutic efficacy against EGFR-expressed human carcinoma via mitochondria-mediated apoptosis
EGFR-targeting, β-defensin-tailored fusion protein exhibits high therapeutic efficacy against EGFR-expressed human carcinoma via mitochondria-mediated apoptosisEGFR-targeting, β-defensin-tailored fusion protein exhibits high therapeutic efficacy against EGFR-expressed human carcinoma via mitochondria-mediated apoptosis, Published online: 16 July 2018; doi:10.1038/s41401-018-0069-8EGFR-targeting, β-defensin-tailored fusion protein exhibits high therapeutic efficacy against EGFR-expressed human carcinoma via mitochondria-mediated apoptosis (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 16, 2018 Category: Drugs & Pharmacology Authors: Wen-Juan Liu Xiu-Jun Liu Jian Xu Liang Li Yi Li Sheng-Hua Zhang Jia-Lin Wang Qing-Fang Miao Yong-Su Zhen Source Type: research