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

CircRNAFisher: a systematic computational approach for de novo circular RNA identification
CircRNAFisher: a systematic computational approach for de novo circular RNA identification, Published online: 16 July 2018; doi:10.1038/s41401-018-0063-1CircRNAFisher: a systematic computational approach for de novo circular RNA identification (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 16, 2018 Category: Drugs & Pharmacology Authors: Guo-yi Jia Duo-lin Wang Meng-zhu Xue Yu-wei Liu Yu-chen Pei Ying-qun Yang Jing-mei Xu Yan-chun Liang Peng Wang Source Type: research

Activation of natural killer T cells contributes to triptolide-induced liver injury in mice
Activation of natural killer T cells contributes to triptolide-induced liver injury in mice, Published online: 16 July 2018; doi:10.1038/s41401-018-0084-9Activation of natural killer T cells contributes to triptolide-induced liver injury in mice (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 16, 2018 Category: Drugs & Pharmacology Authors: Xin-zhi Wang Ru-feng Xue Shen-ye Zhang Ya-ting Zheng Lu-yong Zhang Zhen-zhou Jiang Source Type: research

Isoalantolactone suppresses LPS-induced inflammation by inhibiting TRAF6 ubiquitination and alleviates acute lung injury
Isoalantolactone suppresses LPS-induced inflammation by inhibiting TRAF6 ubiquitination and alleviates acute lung injury, Published online: 16 July 2018; doi:10.1038/s41401-018-0061-3Isoalantolactone suppresses LPS-induced inflammation by inhibiting TRAF6 ubiquitination and alleviates acute lung injury (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 16, 2018 Category: Drugs & Pharmacology Authors: Yun-he Ding Yun-duan Song Ya-xian Wu Hui-qiong He Tian-hong Yu Yu-dong Hu De-peng Zhang Hong-chao Jiang Kai-kai Yu Xiao-zong Li Lei Sun Feng Qian Source Type: research

Wnt signaling pathways in myocardial infarction and the therapeutic effects of Wnt pathway inhibitors.
Abstract Myocardial infarction (MI) is one of the most serious health threats, resulting in huge physical and economic burdens worldwide. Wnt signaling pathways play an important role in developmental processes such as tissue patterning, cell differentiation and cell division. Appropriate regulation of the activities of Wnt signaling pathways is also important for heart development and healing in post-MI heart. Moreover, Wnt pathway inhibitors have been identified as novel antitumor drugs and applied in ongoing clinical trials. This research progress has generated increasing interests for investigating the effects...
Source: Acta Pharmacologica Sinica - July 12, 2018 Category: Drugs & Pharmacology Authors: Fu WB, Wang WE, Zeng CY Tags: Acta Pharmacol Sin Source Type: research

Integrating endocannabinoid signaling in the regulation of anxiety and depression.
Abstract Brain endogenous cannabinoid (eCB) signaling seems to harmonize appropriate behavioral responses, which are essential for the organism's long-term viability and homeostasis. Dysregulation of eCB signaling contributes to negative emotional states and increased stress responses. An understanding of the underlying neural cell populations and neural circuit regulation will enable the development of therapeutic strategies to mitigate behavioral maladaptation and provide insight into the influence of eCB on the neural circuits involved in anxiety and depression. This review focuses on recent evidence ...
Source: Acta Pharmacologica Sinica - July 12, 2018 Category: Drugs & Pharmacology Authors: Yin AQ, Wang F, Zhang X Tags: Acta Pharmacol Sin Source Type: research

Sevoflurane postconditioning protects against myocardial ischemia/reperfusion injury by restoring autophagic flux via an NO-dependent mechanism.
In this study, we examined the effects of sevoflurane on nitric oxide (NO) release and autophagic flux during the myocardial ischemia/reperfusion (I/R) injury in rats in vivo and ex vivo. Male rats were subjected to 30 min ischemia and 2 h reperfusion in the presence or absence of sevoflurane (1.0 minimum alveolar concentration) during the first 15 min of reperfusion. We found that SPC significantly improved hemodynamic performance after reperfusion, alleviated postischemic myocardial infarction, reduced nicotinamide adenine dinucleotide content loss, and cytochrome c release in heart tissues. Furtherm...
Source: Acta Pharmacologica Sinica - July 12, 2018 Category: Drugs & Pharmacology Authors: Qiao SG, Sun Y, Sun B, Wang A, Qiu J, Hong L, An JZ, Wang C, Zhang HL Tags: Acta Pharmacol Sin Source Type: research

Perivascular adipose tissue dysfunction aggravates adventitial remodeling in obese mini pigs via NLRP3 inflammasome/IL-1 signaling pathway.
In this study, we investigated whether and how obesity-induced PVAT dysfunction affected adventitia remodeling in early vascular injury stages. Mini pigs were fed a high sugar and fat diet for 6 months to induce metabolic syndrome and obesity. In the mini pigs, left carotid vascular injury was then generated using balloon dilation. Compared with normal mini pigs, obese mini pigs displayed significantly enhanced vascular injury-induced adventitial responses, evidenced by adventitia fibroblast (AF) proliferation and differentiation, and adventitia fibrosis, as well as exacerbated PVAT dysfunction characterized by increased a...
Source: Acta Pharmacologica Sinica - July 12, 2018 Category: Drugs & Pharmacology Authors: Zhu X, Zhang HW, Chen HN, Deng XJ, Tu YX, Jackson AO, Qing JN, Wang AP, Patel V, Yin K Tags: Acta Pharmacol Sin Source Type: research

Thymopentin-loaded phospholipid-based phase separation gel with long-lasting immunomodulatory effects: in vitro and in vivo studies.
Abstract Thymopentin (TP5) is an effective immunomodulatory agent for autoimmune disease that has been used clinically for decades. However, its application is greatly limited by its extremely short half-life in vivo, poor membrane permeability and extensive metabolism in gastrointestinal tract, resulting in repeated injection and poor patient compliance. In the present study, we developed a TP5-loaded, phospholipid-based phase separation gel (PPSG) to achieve sustained drug release profile and long-lasting therapeutic effects. We firstly demonstrated the physiochemical characteristics of PPSG before and after pha...
Source: Acta Pharmacologica Sinica - July 12, 2018 Category: Drugs & Pharmacology Authors: Zhang T, Qin XY, Cao X, Li WH, Gong T, Zhang ZR Tags: Acta Pharmacol Sin Source Type: research

Thymopentin-loaded phospholipid-based phase separation gel with long-lasting immunomodulatory effects: in vitro and in vivo studies
Thymopentin-loaded phospholipid-based phase separation gel with long-lasting immunomodulatory effects: in vitro and in vivo studies, Published online: 12 July 2018; doi:10.1038/s41401-018-0085-8Thymopentin-loaded phospholipid-based phase separation gel with long-lasting immunomodulatory effects: in vitro and in vivo studies (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 12, 2018 Category: Drugs & Pharmacology Authors: Ting Zhang Xian-yan Qin Xi Cao Wen-hao Li Tao Gong Zhi-rong Zhang Source Type: research

Wnt signaling pathways in myocardial infarction and the therapeutic effects of Wnt pathway inhibitors
Wnt signaling pathways in myocardial infarction and the therapeutic effects of Wnt pathway inhibitors, Published online: 12 July 2018; doi:10.1038/s41401-018-0060-4Wnt signaling pathways in myocardial infarction and the therapeutic effects of Wnt pathway inhibitors (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 12, 2018 Category: Drugs & Pharmacology Authors: Wen-bin Fu Wei Eric Wang Chun-yu Zeng Source Type: research

Perivascular adipose tissue dysfunction aggravates adventitial remodeling in obese mini pigs via NLRP3 inflammasome/IL-1 signaling pathway
Perivascular adipose tissue dysfunction aggravates adventitial remodeling in obese mini pigs via NLRP3 inflammasome/IL-1 signaling pathway, Published online: 12 July 2018; doi:10.1038/s41401-018-0068-9Perivascular adipose tissue dysfunction aggravates adventitial remodeling in obese mini pigs via NLRP3 inflammasome/IL-1 signaling pathway (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 12, 2018 Category: Drugs & Pharmacology Authors: Xiao Zhu Hong-wen Zhang Hai-nan Chen Xiao-jun Deng Yi-xuan Tu Ampadu O. Jackson Ji-na Qing Ai-ping Wang Vaibhav Patel Kai Yin Source Type: research

Sevoflurane postconditioning protects against myocardial ischemia/reperfusion injury by restoring autophagic flux via an NO-dependent mechanism
Sevoflurane postconditioning protects against myocardial ischemia/reperfusion injury by restoring autophagic flux via an NO-dependent mechanism, Published online: 12 July 2018; doi:10.1038/s41401-018-0066-ySevoflurane postconditioning protects against myocardial ischemia/reperfusion injury by restoring autophagic flux via an NO-dependent mechanism (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 12, 2018 Category: Drugs & Pharmacology Authors: Shi-gang Qiao Ying Sun Bo Sun An Wang Jia Qiu Lei Hong Jian-zhong An Chen Wang Hui-ling Zhang Source Type: research

Integrating endocannabinoid signaling in the regulation of anxiety and depression
Integrating endocannabinoid signaling in the regulation of anxiety and depression, Published online: 12 July 2018; doi:10.1038/s41401-018-0051-5Integrating endocannabinoid signaling in the regulation of anxiety and depression (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 12, 2018 Category: Drugs & Pharmacology Authors: An-qi Yin Feng Wang Xia Zhang Source Type: research

Expression of the oxygen-sensitive transcription factor subunit HIF-1 α in patients suffering from secondary Raynaud syndrome.
We examined the regulation of HIF-1α, its target heme oxygenase-1 (HMOX-1), and the serum levels of the HIF-1α protein in a subset of patients as well as in ten healthy individuals. The expression of HIF-1α and HMOX-1 in monocytes was measured using absolute plasmid-based quantitative real-time PCR, whereas serum HIF-1α levels were measured with ELISA. Samples were taken at the time of randomization and after 24 weeks. We found that HIF-1α and HMOX-1 mRNA expression in monocytes and serum HIF-1α protein levels were significantly higher in the SS/RS patients compared to the healthy contro...
Source: Acta Pharmacologica Sinica - July 10, 2018 Category: Drugs & Pharmacology Authors: Heger LA, Kerber M, Hortmann M, Robinson S, Mauler M, Stallmann D, Duerschmied D, Bode C, Hehrlein C, Ahrens I Tags: Acta Pharmacol Sin Source Type: research

Developmental and behavioral effects in neonatal and adult mice following prenatal activation of endocannabinoid receptors by capsaicin.
In this study, pregnant BALBc mice were administered capsaicin (1.0 or 4.0 mg/kg, i.p.) during the second week of gestation. Developmental effects of prenatal exposure to capsaicin were assessed in neonates, and behavioral effects were assessed in adult offspring. Gender- and dose-specific variations in ultrasonic vocalizations, weight gain, righting reflex, and general activity of the pups were observed. Prenatal exposure to capsaicin altered plus-maze performance, especially with further exogenous capsaicin challenge. Furthermore, dose- and gender-specific effects were evident in the conditioned place preference/a...
Source: Acta Pharmacologica Sinica - July 10, 2018 Category: Drugs & Pharmacology Authors: Perchuk A, Bierbower SM, Canseco-Alba A, Mora Z, Tyrell L, Joshi N, Schanz N, Gould GG, Onaivi ES Tags: Acta Pharmacol Sin Source Type: research

Cancer immune checkpoint blockade therapy and its associated autoimmune cardiotoxicity.
Abstract The immune checkpoint molecules are emerged in the evolution to protect the host from self-attacks by activated T cells. However, cancer cells, as a strategy to survive and expand, can hijack these molecules and mechanisms to suppress T cell-mediated immune responses. Therefore, an idea of blocking the checkpoint molecules to enhance the anti-tumor activities of the host immune system has been developed and applied to the cancer therapy after discovery of the inhibitory T cell co-receptor, cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and further enhanced on the identification of PD-1 and its liga...
Source: Acta Pharmacologica Sinica - July 10, 2018 Category: Drugs & Pharmacology Authors: Zhang JC, Chen WD, Alvarez JB, Jia K, Shi L, Wang Q, Zou N, He K, Zhu H Tags: Acta Pharmacol Sin Source Type: research

Inhibitory effects of lappaconitine on the neuronal isoforms of voltage-gated sodium channels.
Abstract Lappaconitine (LA) has been widely used for postoperative and cancer pain control. LA exhibits excellent analgesic activity with a longer effective time than common local anesthetics such as tetracaine and bupivacaine. However, the mechanisms underlying the featured analgesic activity of LA remain largely unknown. Here, we report that LA is an inhibitor of voltage-gated sodium channel 1.7 (Nav1.7) stably expressed in human embryonic kidney (HEK293) cells. LA inhibited Nav1.7 in a voltage-dependent manner with an IC50 value (with 95% confidence limits) of 27.67 (15.68-39.66) µmol/L when the ce...
Source: Acta Pharmacologica Sinica - July 10, 2018 Category: Drugs & Pharmacology Authors: Li YF, Zheng YM, Yu Y, Gan Y, Gao ZB Tags: Acta Pharmacol Sin Source Type: research

mTORC2 facilitates endothelial cell senescence by suppressing Nrf2 expression via the Akt/GSK-3 β/C/EBPα signaling pathway.
In this study we investigated the role and molecular mechanisms of mTORC2 in endothelial senescence. A replicative senescence model and H2O2-induced premature senescence model were established in primary cultured human umbilical vein endothelial cells (HUVECs). In these senescence models, the formation and activation of mTORC2 were significantly increased, evidenced by the increases in binding of Rictor (the essential component of mTORC2) to mTOR, phosphorylation of mTOR at Ser2481 and phosphorylation of Akt (the effector of mTORC2) at Ser473. Knockdown of Rictor or treatment with the Akt inhibitor MK-2206 attenuated senes...
Source: Acta Pharmacologica Sinica - July 10, 2018 Category: Drugs & Pharmacology Authors: Yang HW, Hong HL, Luo WW, Dai CM, Chen XY, Wang LP, Li Q, Li ZQ, Liu PQ, Li ZM Tags: Acta Pharmacol Sin Source Type: research

Ganoderma lucidum extract ameliorates MPTP-induced parkinsonism and protects dopaminergic neurons from oxidative stress via regulating mitochondrial function, autophagy, and apoptosis.
In this study, we investigated the neuroprotective effects of GL extract (GLE) and the underlying mechanisms in the classic MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced mouse model of PD. Mice were injected with MPTP to induce parkinsonism. Then the mice were administered GLE (400 mg kg-1 d-1, ig) for 4 weeks. We observed that GLE administration significantly improved locomotor performance and increased tyrosine hydroxylase expression in the substantia nigra pars compact (SNpc) of MPTP-treated mice. In in vitro study, treatment of neuroblastoma neuro-2a cells with 1-methyl-4-phenylpyridin...
Source: Acta Pharmacologica Sinica - July 10, 2018 Category: Drugs & Pharmacology Authors: Ren ZL, Wang CD, Wang T, Ding H, Zhou M, Yang N, Liu YY, Chan P Tags: Acta Pharmacol Sin Source Type: research

High-throughput screening campaigns against a PI3K α isoform bearing the H1047R mutation identified potential inhibitors with novel scaffolds.
High-throughput screening campaigns against a PI3Kα isoform bearing the H1047R mutation identified potential inhibitors with novel scaffolds. Acta Pharmacol Sin. 2018 Jul 10;: Authors: Wang J, Gong GQ, Zhou Y, Lee WJ, Buchanan CM, Denny WA, Rewcastle GW, Kendall JD, Dickson JMJ, Flanagan JU, Shepherd PR, Yang DH, Wang MW Abstract The phosphatidylinositol 3-kinase (PI3K) pathway is involved in many cellular functions including cell growth, metabolism, and transformation. Hyperactivation of this pathway contributes to tumorigenesis, therefore, PI3K is a major target for anticancer drug discovery. ...
Source: Acta Pharmacologica Sinica - July 10, 2018 Category: Drugs & Pharmacology Authors: Wang J, Gong GQ, Zhou Y, Lee WJ, Buchanan CM, Denny WA, Rewcastle GW, Kendall JD, Dickson JMJ, Flanagan JU, Shepherd PR, Yang DH, Wang MW Tags: Acta Pharmacol Sin Source Type: research

Low serum osteocalcin levels are correlated with left ventricular systolic dysfunction and cardiac death in Chinese men.
In this study, we investigated the value of serum osteocalcin levels in predicting left ventricular systolic dysfunction and cardiac death. A total of 258 patients in the Department of Cardiology were included. Two-dimensional echocardiography was performed in all the subjects. The cardiac death of subjects occurring with a median follow-up of 4.6 years was informed via phone calls or the electronic medical records. The serum osteocalcin levels were measured using electrochemiluminescent immunoassay. We found that the median left ventricular ejection fractions (LVEFs) were 62% in men and 63% in women. In the men with a LVE...
Source: Acta Pharmacologica Sinica - July 10, 2018 Category: Drugs & Pharmacology Authors: Zhang XL, Shen Y, Ma XJ, Lu ZG, Xu YT, Xiong Q, Bao YQ Tags: Acta Pharmacol Sin Source Type: research

Inhibitory effects of lappaconitine on the neuronal isoforms of voltage-gated sodium channels
Inhibitory effects of lappaconitine on the neuronal isoforms of voltage-gated sodium channels, Published online: 10 July 2018; doi:10.1038/s41401-018-0067-xInhibitory effects of lappaconitine on the neuronal isoforms of voltage-gated sodium channels (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 10, 2018 Category: Drugs & Pharmacology Authors: Yan-fen Li Yue-ming Zheng Yong Yu Yong Gan Zhao-bing Gao Source Type: research

Cancer immune checkpoint blockade therapy and its associated autoimmune cardiotoxicity
Cancer immune checkpoint blockade therapy and its associated autoimmune cardiotoxicity, Published online: 10 July 2018; doi:10.1038/s41401-018-0062-2Cancer immune checkpoint blockade therapy and its associated autoimmune cardiotoxicity (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 10, 2018 Category: Drugs & Pharmacology Authors: Jiu-cheng Zhang Wei-dong Chen Jean Bustamante Alvarez Kelly Jia Lei Shi Qiang Wang Ning Zou Kai He Hua Zhu Source Type: research

Expression of the oxygen-sensitive transcription factor subunit HIF-1α in patients suffering from secondary Raynaud syndrome
Expression of the oxygen-sensitive transcription factor subunit HIF-1α in patients suffering from secondary Raynaud syndromeExpression of the oxygen-sensitive transcription factor subunit HIF-1α in patients suffering from secondary Raynaud syndrome, Published online: 10 July 2018; doi:10.1038/s41401-018-0055-1Expression of the oxygen-sensitive transcription factor subunit HIF-1α in patients suffering from secondary Raynaud syndrome (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 10, 2018 Category: Drugs & Pharmacology Authors: Lukas Andreas Heger Mark Kerber Marcus Hortmann Samuel Robinson Maximilian Mauler Daniela Stallmann Daniel Duerschmied Christoph Bode Christoph Hehrlein Ingo Ahrens Source Type: research

Ganoderma lucidum extract ameliorates MPTP-induced parkinsonism and protects dopaminergic neurons from oxidative stress via regulating mitochondrial function, autophagy, and apoptosis
Ganoderma lucidum extract ameliorates MPTP-induced parkinsonism and protects dopaminergic neurons from oxidative stress via regulating mitochondrial function, autophagy, and apoptosis, Published online: 10 July 2018; doi:10.1038/s41401-018-0077-8Ganoderma lucidum extract ameliorates MPTP-induced parkinsonism and protects dopaminergic neurons from oxidative stress via regulating mitochondrial function, autophagy, and apoptosis (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 10, 2018 Category: Drugs & Pharmacology Authors: Zhi-li Ren Chao-dong Wang Tao Wang Hui Ding Ming Zhou Nan Yang Yan-yong Liu Piu Chan Source Type: research

High-throughput screening campaigns against a PI3Kα isoform bearing the H1047R mutation identified potential inhibitors with novel scaffolds
High-throughput screening campaigns against a PI3Kα isoform bearing the H1047R mutation identified potential inhibitors with novel scaffoldsHigh-throughput screening campaigns against a PI3Kα isoform bearing the H1047R mutation identified potential inhibitors with novel scaffolds, Published online: 10 July 2018; doi:10.1038/s41401-018-0057-zHigh-throughput screening campaigns against a PI3Kα isoform bearing the H1047R mutation identified potential inhibitors with novel scaffolds (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 10, 2018 Category: Drugs & Pharmacology Authors: Jia Wang Grace Qun Gong Yan Zhou Woo-Jeong Lee Christina Maree Buchanan William Alexander Denny Gordon William Rewcastle Jackie Diane Kendall James Michael Jeremy Dickson Jack Urquhart Flanagan Peter Robin Shepherd De-Hua Yang Ming-Wei Wang Source Type: research

Developmental and behavioral effects in neonatal and adult mice following prenatal activation of endocannabinoid receptors by capsaicin
Developmental and behavioral effects in neonatal and adult mice following prenatal activation of endocannabinoid receptors by capsaicin, Published online: 10 July 2018; doi:10.1038/s41401-018-0073-zDevelopmental and behavioral effects in neonatal and adult mice following prenatal activation of endocannabinoid receptors by capsaicin (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 10, 2018 Category: Drugs & Pharmacology Authors: Alex Perchuk Sonya M. Bierbower Ana Canseco-Alba Zoila Mora Lauren Tyrell Neal Joshi Norman Schanz Georgianna G. Gould Emmanuel S. Onaivi Source Type: research

Low serum osteocalcin levels are correlated with left ventricular systolic dysfunction and cardiac death in Chinese men
Low serum osteocalcin levels are correlated with left ventricular systolic dysfunction and cardiac death in Chinese men, Published online: 10 July 2018; doi:10.1038/s41401-018-0080-0Low serum osteocalcin levels are correlated with left ventricular systolic dysfunction and cardiac death in Chinese men (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 10, 2018 Category: Drugs & Pharmacology Authors: Xue-li Zhang Yun Shen Xiao-jing Ma Zhi-gang Lu Yi-ting Xu Qin Xiong Yu-qian Bao Source Type: research

mTORC2 facilitates endothelial cell senescence by suppressing Nrf2 expression via the Akt/GSK-3β/C/EBPα signaling pathway
mTORC2 facilitates endothelial cell senescence by suppressing Nrf2 expression via the Akt/GSK-3β/C/EBPα signaling pathwaymTORC2 facilitates endothelial cell senescence by suppressing Nrf2 expression via the Akt/GSK-3β/C/EBPα signaling pathway, Published online: 10 July 2018; doi:10.1038/s41401-018-0079-6mTORC2 facilitates endothelial cell senescence by suppressing Nrf2 expression via the Akt/GSK-3β/C/EBPα signaling pathway (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 10, 2018 Category: Drugs & Pharmacology Authors: Han-wei Yang Hui-ling Hong Wen-wei Luo Chun-mei Dai Xin-yi Chen Lu-ping Wang Qian Li Zi-qing Li Pei-qing Liu Zhuo-ming Li Source Type: research

Repurposing matrine for the treatment of hepatosteatosis and associated disorders in glucose homeostasis in mice.
Abstract The present study investigated the efficacy of the hepatoprotective drug matrine (Mtr) for its new application for hepatosteatosis and associated disorders in glucose homeostasis. The study was performed in two nutritional models of hepatosteatosis in mice with various abnormal glucose homeostasis: (1) high-fructose diet (HFru) induced hepatosteatosis and glucose intolerance from hepatic, and (2) hepatosteatosis and hyperglycemia induced by high-fat (HF) diet in combination with low doses of streptozotocin (STZ). Administration of Mtr (100 mg/kg every day in diet for 4 weeks) abolished HFru-induced...
Source: Acta Pharmacologica Sinica - July 6, 2018 Category: Drugs & Pharmacology Authors: Mazhari A, Zeng XY, Zhou X, Li S, Xu J, Tan W, Vlahos R, Robinson S, Ye JM Tags: Acta Pharmacol Sin Source Type: research

Repurposing matrine for the treatment of hepatosteatosis and associated disorders in glucose homeostasis in mice
Repurposing matrine for the treatment of hepatosteatosis and associated disorders in glucose homeostasis in mice, Published online: 06 July 2018; doi:10.1038/s41401-018-0016-8Repurposing matrine for the treatment of hepatosteatosis and associated disorders in glucose homeostasis in mice (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 6, 2018 Category: Drugs & Pharmacology Authors: Ali Mazhari Xiao-Yi Zeng Xiu Zhou Songpei Li Jun Xu Wen Tan Ross Vlahos Stephen Robinson Ji-Ming YE Source Type: research

Apatinib, a selective VEGFR2 inhibitor, improves the delivery of chemotherapeutic agents to tumors by normalizing tumor vessels in LoVo colon cancer xenograft mice.
In conclusion, Apa may improve the effective perfusion of tumor vessels and increase the intratumoral distribution of ADR in a certain time window via normalizing tumor vessels. This normalization window (7 to 10 days of treatment) may contribute to develop a regimen of combined medication in clinic use of Apa. PMID: 29977004 [PubMed - as supplied by publisher] (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 5, 2018 Category: Drugs & Pharmacology Authors: Zhou K, Zhang JW, Wang QZ, Liu WY, Liu JL, Yao L, Cai MM, Ni SY, Cai QY, Wang GJ, Zhou F Tags: Acta Pharmacol Sin Source Type: research

ClC-3 promotes angiotensin II-induced reactive oxygen species production in endothelial cells by facilitating Nox2 NADPH oxidase complex formation.
In this study we investigated the effects and mechanisms of ClC-3 on NADPH oxidase activation and ROS generation in endothelial cells. Treatment with angiotensin II (Ang II, 1 μmol/L) significantly elevated ClC-3 expression in cultured human umbilical vein endothelial cells (HUVECs). Furthermore, Ang II treatment increased ROS production and NADPH oxidase activity, an effect that could be significantly inhibited by knockdown of ClC-3, and further enhanced by overexpression of ClC-3. SA-β-galactosidase staining showed that ClC-3 silencing abolished Ang II-induced HUVEC senescence, whereas ClC-3 overexpression...
Source: Acta Pharmacologica Sinica - July 5, 2018 Category: Drugs & Pharmacology Authors: Liang GZ, Cheng LM, Chen XF, Li YJ, Li XL, Guan YY, Du YH Tags: Acta Pharmacol Sin Source Type: research

Apatinib, a selective VEGFR2 inhibitor, improves the delivery of chemotherapeutic agents to tumors by normalizing tumor vessels in LoVo colon cancer xenograft mice
Apatinib, a selective VEGFR2 inhibitor, improves the delivery of chemotherapeutic agents to tumors by normalizing tumor vessels in LoVo colon cancer xenograft mice, Published online: 05 July 2018; doi:10.1038/s41401-018-0058-yApatinib, a selective VEGFR2 inhibitor, improves the delivery of chemotherapeutic agents to tumors by normalizing tumor vessels in LoVo colon cancer xenograft mice (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 5, 2018 Category: Drugs & Pharmacology Authors: Kai Zhou Jing-wei Zhang Qi-zhi Wang Wen-yue Liu Jia-li Liu Lan Yao Ming-min Cai Sui-ying Ni Qing-yun Cai Guang-ji Wang Fang Zhou Source Type: research

ClC-3 promotes angiotensin II-induced reactive oxygen species production in endothelial cells by facilitating Nox2 NADPH oxidase complex formation
ClC-3 promotes angiotensin II-induced reactive oxygen species production in endothelial cells by facilitating Nox2 NADPH oxidase complex formation, Published online: 05 July 2018; doi:10.1038/s41401-018-0072-0ClC-3 promotes angiotensin II-induced reactive oxygen species production in endothelial cells by facilitating Nox2 NADPH oxidase complex formation (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 5, 2018 Category: Drugs & Pharmacology Authors: Guo-zheng Liang Li-min Cheng Xing-feng Chen Yue-jiao Li Xiao-long Li Yong-yuan Guan Yan-hua Du Source Type: research

Identification of compound D2923 as a novel anti-tumor agent targeting CSF1R.
Abstract Colony-stimulating factor 1 receptor (CSF1R) plays a critical role in promoting tumor progression in various types of tumors. Here, we identified D2923 as a novel and selective inhibitor of CSF1R and explored its antitumor activity both in vitro and in vivo. D2923 potently inhibited CSF1R in vitro kinase activity with an IC50 value of 0.3 nM. It exhibited 10- to 300-fold less potency against a panel of kinases tested. D2923 markedly blocked CSF-1-induced activation of CSF1R and its downstream signaling transduction in THP-1 and RAW264.7 macrophages and thus inhibited the in vitro growth of macropha...
Source: Acta Pharmacologica Sinica - July 3, 2018 Category: Drugs & Pharmacology Authors: Liu YQ, Wang YN, Lu XY, Tong LJ, Li Y, Zhang T, Xun QJ, Feng F, Chen YZ, Su Y, Shen YY, Chen Y, Geng MY, Ding K, Li YL, Xie H, Ding J Tags: Acta Pharmacol Sin Source Type: research

Identification of compound D2923 as a novel anti-tumor agent targeting CSF1R
Identification of compound D2923 as a novel anti-tumor agent targeting CSF1R, Published online: 03 July 2018; doi:10.1038/s41401-018-0056-0Identification of compound D2923 as a novel anti-tumor agent targeting CSF1R (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 3, 2018 Category: Drugs & Pharmacology Authors: Ying-Qiang Liu Ya-Nan Wang Xiao-Yun Lu Lin-Jiang Tong Yan Li Tao Zhang Qiu-Ju Xun Fang Feng Yu-Zhe Chen Yi Su Yan-Yan Shen Yi Chen Mei-Yu Geng Ke Ding Yan-Li Li Hua Xie Jian Ding Source Type: research

Cannabinoid CB1 receptor neutral antagonist AM4113 inhibits heroin self-administration without depressive side effects in rats.
In this study, we demonstrated that systemic administration of AM4113 (3 and 10 mg/kg) dose-dependently inhibited the self-administration of intravenous heroin but not cocaine or methamphetamine, whereas SR141716A (3 and 10 mg/kg) dose-dependently inhibited the self-administration of heroin and methamphetamine but not cocaine. In the electrical brain-stimulation reward (BSR) paradigm, SR141716A (3 and 10 mg/kg) dose-dependently increased the BSR stimulation threshold (i.e., decreased the stimulation reward), but AM4113 had no effect on BSR at the same doses, suggesting that SR141716A may produce aversi...
Source: Acta Pharmacologica Sinica - July 2, 2018 Category: Drugs & Pharmacology Authors: He XH, Jordan CJ, Vemuri K, Bi GH, Zhan J, Gardner EL, Makriyannis A, Wang YL, Xi ZX Tags: Acta Pharmacol Sin Source Type: research

CB2 receptor antibody signal specificity: correlations with the use of partial CB2-knockout mice and anti-rat CB2 receptor antibodies.
Abstract Cannabinoid CB1 receptors are highly expressed in the brain and functionally modulate presynaptic neurotransmitter release, while cannabinoid CB2 receptors (CB2Rs) were initially identified in the spleen and regarded as peripheral cannabinoid receptors. Recently, growing evidence indicates the presence of functional CB2Rs in the brain. However, this finding is disputed because of the specificity of CB2R antibody signals. We used two strains of currently available partial CB2-knockout (CB2-KO) mice as controls, four anti-rat or anti-mouse CB2R antibodies, and mRNA quantification to further address this iss...
Source: Acta Pharmacologica Sinica - July 2, 2018 Category: Drugs & Pharmacology Authors: Zhang HY, Shen H, Jordan CJ, Liu QR, Gardner EL, Bonci A, Xi ZX Tags: Acta Pharmacol Sin Source Type: research

CB2 receptor antibody signal specificity: correlations with the use of partial CB2-knockout mice and anti-rat CB2 receptor antibodies
CB2 receptor antibody signal specificity: correlations with the use of partial CB2-knockout mice and anti-rat CB2 receptor antibodies, Published online: 02 July 2018; doi:10.1038/s41401-018-0037-3CB2 receptor antibody signal specificity: correlations with the use of partial CB2-knockout mice and anti-rat CB2 receptor antibodies (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 2, 2018 Category: Drugs & Pharmacology Authors: Hai-ying Zhang Hui Shen Chloe J. Jordan Qing-rong Liu Eliot L. Gardner Antonello Bonci Zheng-xiong Xi Source Type: research

Cannabinoid CB1 receptor neutral antagonist AM4113 inhibits heroin self-administration without depressive side effects in rats
Cannabinoid CB1 receptor neutral antagonist AM4113 inhibits heroin self-administration without depressive side effects in rats, Published online: 02 July 2018; doi:10.1038/s41401-018-0059-xCannabinoid CB1 receptor neutral antagonist AM4113 inhibits heroin self-administration without depressive side effects in rats (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - July 2, 2018 Category: Drugs & Pharmacology Authors: Xiang-hu He Chloe J. Jordan Kiran Vemuri Guo-hua Bi Jia Zhan Eliot L. Gardner Alexandros Makriyannis Yan-lin Wang Zheng-xiong Xi Source Type: research

Biomarkers for individualized dosage adjustments in immunosuppressive therapy using calcineurin inhibitors after organ transplantation.
Abstract Calcineurin inhibitors (CNIs), such as cyclosporine A and tacrolimus, are widely used immunosuppressive agents for the prevention of post-transplantation rejection and have improved 1-year graft survival rates by up to 90%. However, CNIs can induce severe reactions, such as acute or chronic allograft nephropathy, hypertension, and neurotoxicity. Because CNIs have varied bioavailabilities, narrow therapeutic ranges, and individual propensities for toxic effects, therapeutic drug monitoring is necessary for all CNIs. Identifying the genetic polymorphisms in drug-metabolizing enzymes will help to determine p...
Source: Acta Pharmacologica Sinica - June 27, 2018 Category: Drugs & Pharmacology Authors: Fu R, Tajima S, Suetsugu K, Watanabe H, Egashira N, Masuda S Tags: Acta Pharmacol Sin Source Type: research

Design and evaluation of glomerulus mesangium-targeted PEG-PLGA nanoparticles loaded with dexamethasone acetate.
Abstract Mesangial proliferative glomerulonephritis (MsPGN), one of the most common glomerulonephritis pathological types, often leads to end-stage renal disease over a prolonged period. But the current treatment of MsPGN is non-specific and causes serious side effects, thus novel therapeutics and targeting strategies are urgently demanded. By combining the advantages of PEG-PLGA nanoparticles and the size selection mechanism of renal glomerulus, we designed and developed a novel PEG-PLGA nanoparticle delivery system capable of delivering dexamethasone acetate (A-DEX) into glomerular mesangium. We determined that ...
Source: Acta Pharmacologica Sinica - June 27, 2018 Category: Drugs & Pharmacology Authors: Li S, Zeng YC, Peng K, Liu C, Zhang ZR, Zhang L Tags: Acta Pharmacol Sin Source Type: research