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    6197 results match your criteria Acta Pharmacologica Sinica[Journal]

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    Carnosine suppresses oxygen-glucose deprivation/recovery-induced proliferation and migration of reactive astrocytes of rats in vitro.
    Acta Pharmacol Sin 2017 Sep 21. Epub 2017 Sep 21.
    Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life sciences, Wenzhou Medical University, Wenzhou 325035, China.
    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. Read More

    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.
    Acta Pharmacol Sin 2017 Sep 21. Epub 2017 Sep 21.
    Department of Clinical Pharmacy, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
    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. Read More

    Omega-3 PUFA ameliorates hyperhomocysteinemia-induced hepatic steatosis in mice by inhibiting hepatic ceramide synthesis.
    Acta Pharmacol Sin 2017 Sep 21. Epub 2017 Sep 21.
    Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education and Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China.
    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. Read More

    Curcumin administration suppresses collagen synthesis in the hearts of rats with experimental diabetes.
    Acta Pharmacol Sin 2017 Sep 14. Epub 2017 Sep 14.
    Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning 437100, China.
    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. Read More

    Triptolide induces Sertoli cell apoptosis in mice via ROS/JNK-dependent activation of the mitochondrial pathway and inhibition of Nrf2-mediated antioxidant response.
    Acta Pharmacol Sin 2017 Sep 14. Epub 2017 Sep 14.
    School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 210009, China.
    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. Read More

    SOMCL-085, a novel multi-targeted FGFR inhibitor, displays potent anticancer activity in FGFR-addicted human cancer models.
    Acta Pharmacol Sin 2017 Sep 14. Epub 2017 Sep 14.
    Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
    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. Read More

    Combing oncolytic adenovirus expressing Beclin-1 with chemotherapy agent doxorubicin synergistically enhances cytotoxicity in human CML cells in vitro.
    Acta Pharmacol Sin 2017 Sep 14. Epub 2017 Sep 14.
    Department of Hematology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
    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. Read More

    Age-related differences in interferon regulatory factor-4 and -5 signaling in ischemic brains of mice.
    Acta Pharmacol Sin 2017 Sep 14. Epub 2017 Sep 14.
    Department of Neurology, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
    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. Read More

    Conversion and pharmacokinetics profiles of a novel pro-drug of 3-n-butylphthalide, potassium 2-(1-hydroxypentyl)-benzoate, in rats and dogs.
    Acta Pharmacol Sin 2017 Sep 14. Epub 2017 Sep 14.
    State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100050, China.
    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. Read More

    (5R)-5-hydroxytriptolide ameliorates anti-glomerular basement membrane glomerulonephritis in NZW mice by regulating Fcγ receptor signaling.
    Acta Pharmacol Sin 2017 Sep 7. Epub 2017 Sep 7.
    Laboratory of Immunology and Virology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
    (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). Read More

    Integrated pharmacokinetic/viral dynamic model for daclatasvir/asunaprevir in treatment of patients with genotype 1 chronic hepatitis C.
    Acta Pharmacol Sin 2017 Sep 7. Epub 2017 Sep 7.
    Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
    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. The IC50 values of DCV and ASV were estimated to be 0. Read More

    Chimeric antigen receptor (CAR)-transduced natural killer cells in tumor immunotherapy.
    Acta Pharmacol Sin 2017 Sep 7. Epub 2017 Sep 7.
    Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Ji-nan 250012, China.
    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. Read More

    Osimertinib (AZD9291) decreases programmed death ligand-1 in EGFR-mutated non-small cell lung cancer cells.
    Acta Pharmacol Sin 2017 Sep 7. Epub 2017 Sep 7.
    State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
    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. Read More

    GOLPH2-regulated oncolytic adenovirus, GD55, exerts strong killing effect on human prostate cancer stem-like cells in vitro and in vivo.
    Acta Pharmacol Sin 2017 Sep 7. Epub 2017 Sep 7.
    Xinyuan Institute of Medicine and Biotechnology, College of Life Sciences Zhejiang Sci-Tech University, Hangzhou 310018, China.
    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. Read More

    Activation of aldehyde dehydrogenase 2 slows down the progression of atherosclerosis via attenuation of ER stress and apoptosis in smooth muscle cells.
    Acta Pharmacol Sin 2017 Aug 31. Epub 2017 Aug 31.
    Department of Cardiology, State Key Laboratory of Kidney Disease, Chinese PLA General Hospital, Beijing 100853, China.
    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. Read More

    Development of a high-throughput fluorescence polarization assay for the discovery of EZH2-EED interaction inhibitors.
    Acta Pharmacol Sin 2017 Aug 31. Epub 2017 Aug 31.
    State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
    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. Read More

    Synthesis and in vitro biological evaluation of thiosulfinate derivatives for the treatment of human multidrug-resistant breast cancer.
    Acta Pharmacol Sin 2017 Aug 31. Epub 2017 Aug 31.
    Discipline of Pharmacy, Graduate School of Health, The University of Technology Sydney, NSW, Australia.
    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. Read More

    Crystal structure-based comparison of two NAMPT inhibitors.
    Acta Pharmacol Sin 2017 Aug 31. Epub 2017 Aug 31.
    Department of Pharmacology, Second Military Medical University, Shanghai 200433, China.
    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. Read More

    YL-0919, a dual 5-HT1A partial agonist and SSRI, produces antidepressant- and anxiolytic-like effects in rats subjected to chronic unpredictable stress.
    Acta Pharmacol Sin 2017 Aug 31. Epub 2017 Aug 31.
    Department of New Drug Evaluation, State Key Laboratory of Toxicology Medical Courtermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
    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. Read More

    CCN3 suppresses TGF-β1-induced extracellular matrix accumulation in human mesangial cells in vitro.
    Acta Pharmacol Sin 2017 Aug 31. Epub 2017 Aug 31.
    Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine.
    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. Read More

    Versatile effects of bacterium-released membrane vesicles on mammalian cells and infectious/inflammatory diseases.
    Acta Pharmacol Sin 2017 Aug 31. Epub 2017 Aug 31.
    Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
    Gram-negative bacterium-released outer-membrane vesicles (OMVs) and Gram-positive bacterium-released membrane vesicles (MVs) share significant similarities with mammalian cell-derived MVs (eg, microvesicles and exosomes) in terms of structure and their biological activities. Recent studies have revealed that bacterial OMVs/MVs could (1) interact with immune cells to regulate inflammatory responses, (2) transport virulence factors (eg, enzymes, DNA and small RNAs) to host cells and result in cell injury, (3) enhance barrier function by stimulating the expression of tight junction proteins in intestinal epithelial cells, (4) upregulate the expression of endothelial cell adhesion molecules, and (5) serve as natural nanocarriers for immunogenic antigens, enzyme support and drug delivery. In addition, OMVs/MVs can enter the systemic circulation and induce a variety of immunological and metabolic responses. Read More

    The ceramide pathway is involved in the survival, apoptosis and exosome functions of human multiple myeloma cells in vitro.
    Acta Pharmacol Sin 2017 Aug 31. Epub 2017 Aug 31.
    Department of Hematology, the Third Xiangya Hospital of Central South University, Changsha 412000, China.
    Multiple myeloma (MM) is characterized by the clonal proliferation of malignant plasma cells and refractoriness to traditional therapies. It has been shown that exosomes are involved in modulating the progression and the metastasis of cancers through microRNAs (miRs). Ceramide is a type of sphingolipid; the ceramide pathway of exosomal secretion has been shown to affect the apoptosis of cancer cells. Read More

    Main active constituent identification in Guanxinjing capsule, a traditional Chinese medicine, for the treatment of coronary heart disease complicated with depression.
    Acta Pharmacol Sin 2017 Aug 31. Epub 2017 Aug 31.
    Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
    Guanxinjing capsules (GXJCs) are used in traditional Chinese medicine as a common therapy for coronary heart disease (CHD) complicated with depression. In this study, we aimed to identify the main active constituents in GXJCs and to investigate the mechanisms of GXJC action on CHD complicated with depression. The chemical constituent profile of the GXJC was identified by UHPLC-LTQ-Orbitrap assay, and oral bioavailability was evaluated to screen the GXJC drug-like chemical constituents. Read More

    Population pharmacokinetics and Bayesian estimation of mycophenolic acid concentrations in Chinese adult renal transplant recipients.
    Acta Pharmacol Sin 2017 Aug 24. Epub 2017 Aug 24.
    Institute of Clinical Pharmacology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China.
    Mycophenolate mofetil (MMF) is an important immunosuppressant used in renal transplantation, and mycophenolic acid (MPA) is the active component released from the ester prodrug MMF. The objective of this study was to investigate the population pharmacokinetics of mycophenolic acid (MPA) following oral administration of MMF in Chinese adult renal transplant recipients and to identify factors that explain MPA pharmacokinetic variability. Pharmacokinetic data for MPA and covariate information were retrospectively collected from 118 patients (79 patients were assigned to the group for building the population pharmacokinetic model, while 39 patients were assigned to the validation group). Read More

    Iron dysregulates APP processing accompanying with sAPPα cellular retention and β-secretase inhibition in rat cortical neurons.
    Acta Pharmacol Sin 2017 Aug 24. Epub 2017 Aug 24.
    CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
    Amyloid precursor protein (APP) and iron both play pivotal roles in the central nervous system, but whether and how iron influences the processing of endogenous APP in neurons remain unclear. Here, we investigated the regulatory effects and underlying mechanisms of iron on non-amyloidogenic and amyloidogenic processing of APP in rat primary cortical neurons. Treatment of the neurons with ferric ammonium citrate (FAC, 100 μmol/L) markedly facilitated the non-amyloidogenic processing of APP, as evidenced by a robust increase in α-secretase-derived carboxy-terminal fragment α (CTFα). Read More

    Pharmacokinetic and metabolomic analyses of the neuroprotective effects of salvianolic acid A in a rat ischemic stroke model.
    Acta Pharmacol Sin 2017 Aug 24. Epub 2017 Aug 24.
    Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
    Salvianolic acid A (SAA), a water-soluble phenolic acid isolated from the root of Dan Shen, displays distinct antioxidant activity and effectiveness in protection against cerebral ischemia/reperfusion (I/R) damage. However, whether SAA can enter the central nervous system and exert its protective effects by directly targeting brain tissue remains unclear. In this study, we evaluated the cerebral protection of SAA in rats subjected to transient middle cerebral artery occlusion (tMCAO) followed by reperfusion. Read More

    Influences of renal function descriptors on population pharmacokinetic modeling of vancomycin in Chinese adult patients.
    Acta Pharmacol Sin 2017 Aug 24. Epub 2017 Aug 24.
    Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
    Vancomycin, a glycopeptide antibiotic for the treatment of grampositive infections, is mainly eliminated via glomerular filtration. Thus, its therapeutic effects are affected predominantly by renal function. The aim of this study was to develop a population pharmacokinetic model of vancomycin for Chinese adult patients and to investigate the influence of different renal function descriptors on the predictability of the model. Read More

    Ginsenosides synergize with mitomycin C in combating human non-small cell lung cancer by repressing Rad51-mediated DNA repair.
    Acta Pharmacol Sin 2017 Aug 24. Epub 2017 Aug 24.
    State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
    The use of ginseng extract as an adjuvant for cancer treatment has been reported in both animal models and clinical applications, but its molecular mechanisms have not been fully elucidated. Mitomycin C (MMC), an anticancer antibiotic used as a first- or second-line regimen in the treatment for non-small cell lung carcinoma (NSCLC), causes serious adverse reactions when used alone. Here, by using both in vitro and in vivo experiments, we provide evidence for an optimal therapy for NSCLC with total ginsenosides extract (TGS), which significantly enhanced the MMC-induced cytotoxicity against NSCLC A549 and PC-9 cells in vitro when used in combination with relatively low concentrations of MMC. Read More

    BCR-ABL1-positive microvesicles malignantly transform human bone marrow mesenchymal stem cells in vitro.
    Acta Pharmacol Sin 2017 Aug 24. Epub 2017 Aug 24.
    Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
    The intercellular communication between leukemia cells and bone marrow mesenchymal stem cells (BM-MSCs) plays more important role in chronic myeloid leukemia (CML) than we previously understood. Recently, we found that microvesicles released from human leukemia cell line K562 (K562-MVs) containing BCR-ABL1 mRNA malignantly transformed normal hematopoietic transplants. Here, we investigated whether K562-MVs contribute to the transformation of human bone marrow mesenchymal stem cells (BM-MSCs). Read More

    MicroRNA-132 suppresses cell proliferation in human breast cancer by directly targeting FOXA1.
    Acta Pharmacol Sin 2017 Aug 17. Epub 2017 Aug 17.
    Department of Otolaryngology Head and Neck Surgery, the Second Hospital of Jilin University, Changchun 130041, China.
    Dysregulation of microRNAs (miRNAs) has been implicated in cancer. Recently, miR-132 has been reported to be downregulated in the tissues of patients with breast cancer. In this study, we investigated the functional role of miR-132 and its direct target FOXA1 in breast cancer cells. Read More

    G3BP2 is involved in isoproterenol-induced cardiac hypertrophy through activating the NF-κB signaling pathway.
    Acta Pharmacol Sin 2017 Aug 17. Epub 2017 Aug 17.
    Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
    The RasGAP SH3 domain-binding proteins (G3BPs) are a family of RNA-binding proteins that can co-ordinate signal transduction and post-transcriptional gene regulation. G3BPs have been shown to be involved in mediating a great diversity of cellular processes such as cell survival, growth, proliferation and apoptosis. But the potential roles of G3BPs in the pathogenesis and progression of cardiovascular diseases remain to be clarified. Read More

    Novel mutations of TCIRG1 cause a malignant and mild phenotype of autosomal recessive osteopetrosis (ARO) in four Chinese families.
    Acta Pharmacol Sin 2017 Aug 17. Epub 2017 Aug 17.
    Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
    Human autosomal recessive osteopetrosis (ARO), also known as infantile malignant osteopetrosis, is a rare genetic bone disorder that often causes death. Mutations in T-cell immune regulator 1 (TCIRG1) are a frequent cause of human ARO. Six additional genes (TNFSF11, TNFRSF11A, CLCN7, OSTM1, SNX10, PLEKHM1) were also found to be associated with human ARO. Read More

    Shikonin induces glioma cell necroptosis in vitro by ROS overproduction and promoting RIP1/RIP3 necrosome formation.
    Acta Pharmacol Sin 2017 Aug 17. Epub 2017 Aug 17.
    Department of Neurosurgery, First Hospital of Jilin University, Changchun 130021, China.
    Necroptosis is a type of programmed necrosis regulated by receptor interacting protein kinase 1 (RIP1) and RIP3. Necroptosis is found to be accompanied by an overproduction of reactive oxygen species (ROS), but the role of ROS in regulation of necroptosis remains elusive. In this study, we investigated how shikonin, a necroptosis inducer for cancer cells, regulated the signaling leading to necroptosis in glinoma cells in vitro. Read More

    Dual roles of QOA-8a in antiosteoporosis: a combination of bone anabolic and anti-resorptive effects.
    Acta Pharmacol Sin 2017 Aug 17. Epub 2017 Aug 17.
    State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
    Osteoporotic treatments have largely depended on antiresorptive or anabolic drugs; but the former also suppresses new bone formation, and the latter only includes human parathyroid hormone. There is no drug that has a dual effect to inhibit bone resorption and to stimulate bone formation simultaneously. Here, we report a small molecule, a quinoxaline derivative of oleanolic acid (QOA-8a) that plays such dual roles in osteoblasts and osteoclasts in the treatment of osteoporosis. Read More

    Molecular mechanisms of the analgesic action of Wu-tou Decoction on neuropathic pain in mice revealed using microarray and network analysis.
    Acta Pharmacol Sin 2017 Aug 17. Epub 2017 Aug 17.
    Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
    Wu-tou Decoction (WTD) is a classic herbal formula in traditional Chinese medicine for the treatment of joint diseases, neuropathic pain (NP) and inflammatory pain. In this study we investigated whether WTD produced analgesic action in a mouse spinal nerve ligation (SNL) model and elucidated the underlying molecular mechanisms. Mice were subjected to SNL and orally treated with WTD (3. Read More

    The novel resveratrol derivative 3,5-diethoxy-3',4'-dihydroxy-trans-stilbene induces mitochondrial ROS-mediated ER stress and cell death in human hepatoma cells in vitro.
    Acta Pharmacol Sin 2017 Aug 10. Epub 2017 Aug 10.
    School of Biological Sciences, University of Ulsan, Ulsan 44610, Korea.
    Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a well-known polyphenol that is present in grapes, peanuts, pine seeds, and several other plants. Resveratrol exerts deleterious effects on various types of human cancer cells. Here, we analyzed the cell death-inducing mechanisms of resveratrol-006 (Res-006), a novel resveratrol derivative in human liver cancer cells in vitro. Read More

    Evaluation of in vitro and in vivo activity of a multityrosine kinase inhibitor, AL3810, against human thyroid cancer.
    Acta Pharmacol Sin 2017 Aug 10. Epub 2017 Aug 10.
    Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
    Thyroid cancer is the most common type of endocrine neoplasia. Despite recent breakthroughs in treatment of the disease, the treatment of advanced, progressive thyroid cancers remains challenging with limited therapeutic options available. In this study, we evaluated a novel and orally bioavailable small-molecule multiple tyrosine kinases inhibitor, AL3810, in preclinical models of thyroid cancer in vitro and in vivo. Read More

    IR-780-loaded polymeric micelles enhance the efficacy of photothermal therapy in treating breast cancer lymphatic metastasis in mice.
    Acta Pharmacol Sin 2017 Aug 10. Epub 2017 Aug 10.
    State Key Laboratory of Drug Research &Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
    Cancer metastasis is responsible for over 90% of breast cancer-related deaths, and inhibiting lymph node metastasis is an option to treat metastatic disease. Herein, we report the use of IR-780-loaded polymeric micelles (IPMs) for effective photothermal therapy (PTT) of breast cancer lymphatic metastasis. The IPMs were nanometer-sized micelles with a mean diameter of 25. Read More

    Resveratrol alleviates diabetic cardiomyopathy in rats by improving mitochondrial function through PGC-1α deacetylation.
    Acta Pharmacol Sin 2017 Aug 3. Epub 2017 Aug 3.
    Department of Pharmacy, the Third Xiangya Hospital of Central South University, Changsha 410013, China.
    Recent evidence shows that resveratrol (RSV) may ameliorate high-glucose-induced cardiac oxidative stress, mitochondrial dysfunction and myocardial fibrosis in diabetes. However, the mechanisms by which RSV regu¬lates mitochondrial function in diabetic cardiomyopathy have not been fully elucidated. Mitochondrial dysfunction contributes to cardiac dysfunction in diabetic patients, which is associated with dysregulation of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α). Read More

    WNK1 is required for proliferation induced by hypotonic challenge in rat vascular smooth muscle cells.
    Acta Pharmacol Sin 2017 Aug 3. Epub 2017 Aug 3.
    Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.
    Hypotonic challenge evoked vascular cell proliferation through activation of volume-regulated Cl(-) channel (VRCC), leading to a decrease in the intracellular Cl(-) concentration ([Cl(-)]i). We hypothesize that the decrease in [Cl(-)]i may activate one or several Cl(-)-sensitive kinases, resulting in a subsequent signaling cascade. In this study we demonstrated that WNK1, a Cl(-)-sensitive kinase, was involved in VRCC-induced proliferative signaling pathway in A10 vascular smooth muscle cells in vitro. Read More

    Sesamin alleviates blood-brain barrier disruption in mice with experimental traumatic brain injury.
    Acta Pharmacol Sin 2017 Aug 3. Epub 2017 Aug 3.
    Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200233, China.
    Sesamin, a major lignan of sesame oil, was reported to have neuroprotective effects in several brain injury models. However, its protective action in maintaining blood-brain barrier (BBB) integrity has not been studied. In this study we investigated the effects of sesamin on the BBB in a mouse model of traumatic brain injury (TBI) and explored the underlying mechanisms. Read More

    Discovery of potent 2,4-difluoro-linker poly(ADP-ribose) polymerase 1 inhibitors with enhanced water solubility and in vivo anticancer efficacy.
    Acta Pharmacol Sin 2017 Aug 3. Epub 2017 Aug 3.
    Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
    Poly (ADP-ribose) polymerase 1 (PARP1) is overexpressed in a variety of cancers, especially in breast and ovarian cancers; tumor cells that are deficient in breast cancer gene 1/2 (BRCA1/2) are highly sensitive to PARP1 inhibition. In this study, we identified a series of 2,4-difluorophenyl-linker analogs (15-55) derived from olaparib as novel PARP1 inhibitors. Four potent analogs 17, 43, 47, and 50 (IC50=2. Read More

    The immunoglobulin D Fc receptor expressed on fibroblast-like synoviocytes from patients with rheumatoid arthritis contributes to the cell activation.
    Acta Pharmacol Sin 2017 Aug 3. Epub 2017 Aug 3.
    Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei 230032, China.
    Immunoglobulin IgD might play an important role in autoimmune diseases, but the function of IgD has remained elusive, despite multiple attempts to define its biological function. Fibroblast-like synoviocytes (FLSs) are specialized cells of the synovium that play a key role in the pathogenesis of rheumatoid arthritis (RA). In this study we explored the possible roles of excessive IgD expression on the function of FLSs from RA patients (RA-FLSs). Read More

    Kappa-opioid receptor agonist U50448H protects against renal ischemia-reperfusion injury in rats via activating the PI3K/Akt signaling pathway.
    Acta Pharmacol Sin 2017 Aug 3. Epub 2017 Aug 3.
    Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai 201499, China.
    Renal ischemia-reperfusion injury (IRI) is regarded as a leading cause of acute kidney failure and renal dysfunction. Previous studies show that kappa opioid receptor (KOR) agonists can attenuate IRI in cardiomycytes and neuronal cells. In this study we explored the effects of a KOR agonist on renal IRI and the underlying mechanisms in vivo and in vitro. Read More

    Acute liver failure enhances oral plasma exposure of zidovudine in rats by downregulation of hepatic UGT2B7 and intestinal P-gp.
    Acta Pharmacol Sin 2017 Aug 3. Epub 2017 Aug 3.
    Center of Drug Metabolism and Pharmacokinetics, College of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
    HIV infection is often associated with liver failure, which alters the pharmacokinetics of many drugs. In this study we investigated whether acute liver failure (ALF) altered the pharmacokinetics of the first-line anti-HIV agent zidovudine (AZT), a P-gp/BCRP substrate, in rats. ALF was induced in rats by injecting thioacetamide (TAA, 300 mg·kg(-1)·d(-1), ip) for 2 days. Read More

    Conformation and dynamics of the C-terminal region in human phosphoglycerate mutase 1.
    Acta Pharmacol Sin 2017 Jul 27. Epub 2017 Jul 27.
    State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
    Phosphoglycerate mutase 1 (PGAM1), an important enzyme in glycolysis, is overexpressed in a number of human cancers, thus has been proposed as a promising metabolic target for cancer treatments. The C-terminal portion of the available crystal structures of PGAM1 and its homologous proteins is partially disordered, as evidenced by weak electron density. In this study, we identified the conformational behavior of the C-terminal region of PGAM1 as well as its role during the catalytic cycle. Read More

    The endoplasmic reticulum stress-autophagy pathway is involved in apelin-13-induced cardiomyocyte hypertrophy in vitro.
    Acta Pharmacol Sin 2017 Jul 27. Epub 2017 Jul 27.
    Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang 421001, China.
    Apelin is the endogenous ligand for the G protein-coupled receptor APJ, and plays important roles in the cardiovascular system. Our previous studies showed that apelin-13 promotes the hypertrophy of H9c2 rat cardiomyocytes through the PI3K-autophagy pathway. The aim of this study was to explore what roles ER stress and autophagy played in apelin-13-induced hypertrophy of cardiomyocytes in vitro. Read More

    Association of bone turnover markers with glucose metabolism in Chinese population.
    Acta Pharmacol Sin 2017 Jul 27. Epub 2017 Jul 27.
    Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
    The association between type 2 diabetes (T2DM) and bone metabolism has been discussed previously but is controversial. In this study we aimed to evaluate the association of bone turnover markers with glucose metabolism in Chinese population, in which 919 males and 4171 postmenopausal females in a region of Shanghai were recruited. Anthropometric and biochemical traits related to glucose and bone metabolism were analyzed. Read More

    D-chiro-inositol effectively attenuates cholestasis in bile duct ligated rats by improving bile acid secretion and attenuating oxidative stress.
    Acta Pharmacol Sin 2017 Jul 27. Epub 2017 Jul 27.
    Key Laboratory of Biotechnology of Antibiotics, the National Health and Family Planning Commission (NHFPC); Department of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
    Cholestatic liver diseases are important causes of liver cirrhosis and liver transplantation, but few drugs are available for treatment. D-chiro-inositol (DCI), an isomer of inositol found in many Leguminosae plants and in animal viscera, is used clinically for the treatment of polycystic ovary syndrome (PCOS) and diabetes mellitus. In this study, we investigated whether DCI exerted an anti-cholestatic effect and its underlying mechanisms. Read More

    A novel allosteric site in casein kinase 2α discovered using combining bioinformatics and biochemistry methods.
    Acta Pharmacol Sin 2017 Jul 27. Epub 2017 Jul 27.
    Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China.
    Casein kinase 2 (CK2) is a highly pleiotropic serine-threonine kinase, which catalyzed phosphorylation of more than 300 proteins that are implicated in regulation of many cellular functions, such as signal transduction, transcriptional control, apoptosis and the cell cycle. On the other hand, CK2 is abnormally elevated in a variety of tumors, and is considered as a promising therapeutic target. The currently available ATP-competitive CK2 inhibitors, however, lack selectivity, which has impeded their development in cancer therapy. Read More

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