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    Resveratrol suppresses doxorubicin-induced cardiotoxicity by disrupting E2F1 mediated autophagy inhibition and apoptosis promotion.
    Biochem Pharmacol 2018 Feb 20. Epub 2018 Feb 20.
    Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China. Electronic address:
    The clinical use of doxorubicin (DOX) is limited by cardiotoxicity, involving the dysregulation of autophagy and apoptosis in the myocardium, which were partly reversed by resveratrol (RSV) supplement. However, a definitive mechanisms accounting for DOX's cardiotoxicity and the protective role of RSV remain poorly defined. The aim of the present study was to clarify the specific role of E2F transcription factor 1(E2F1) in regulating autophagy and apoptosis in DOX-induced cardiotoxicity as well as the protective effects of RSV. Read More

    A fungal metabolite zearalenone as a CFTR inhibitor and potential therapy of secretory diarrheas.
    Biochem Pharmacol 2018 Feb 20. Epub 2018 Feb 20.
    Department of Physiology, Faculty of Science, Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand; Excellent Center for Drug Discovery, Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand; Translational Medicine Graduate Program, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand. Electronic address:
    Overstimulation of CFTR-mediated Clsecretion plays an important role in the pathogenesis of secretory diarrheas, which remain an important global health problem. This study aimed to identify inhibitors of CFTR-mediated Clsecretion from a library of fungus-derived compounds and to evaluate their pharmacological properties and anti-diarrheal utility. We identified zearalenone, 7'-dehydrozearalenone and 8'-hydroxyzearalenone isolated from the seagrass-derived fungus Fusarium sp. Read More

    Lanatoside C inhibits cell proliferation and induces apoptosis through attenuating Wnt/β-catenin/c-Myc signaling pathway in human gastric cancer cell.
    Biochem Pharmacol 2018 Feb 20. Epub 2018 Feb 20.
    Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China.; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou 221004, PR China; Research Center for Cancer Precision Medicine, Department of Laboratory Medicine, Bengbu Medical College, Bengbu 233030, PR China.. Electronic address:
    Gastric cancer is the third common cause of cancer mortality in the world with poor prognosis and high recurrence due to lack of effective medicines. Our studies revealed that lanatoside C, a FDA-approved cardiac glycoside, had an anti-proliferation effect on different human cancer cell lines (MKN-45; SGC-7901; HN4; MCF-7; HepG2) and gastric cell lines MKN-45 and SGC-7901 were the most sensitive cell lines to lanatoside C. MKN-45 cells treated with lanatoside C showed cell cycle arrest at G2/M phase and inhibition of cell migration. Read More

    Lipid bilayer stress in obesity-linked inflammatory and metabolic disorders.
    Biochem Pharmacol 2018 Feb 17. Epub 2018 Feb 17.
    Laboratory of Immunometabolism and Nutrition, GIGA-I3, University of Liège, Liège, Belgium; Laboratory of Virology and Immunology, GIGA-Molecular Biology of Diseases, University of Liège, Liège, Belgium.. Electronic address:
    The maintenance of the characteristic lipid compositions and physicochemical properties of biological membranes is essential for their proper function. Mechanisms allowing to sense and restore membrane homeostasis have been identified in prokaryotes for a long time and more recently in eukaryotes. A membrane remodeling can result from aberrant metabolism as seen in obesity. Read More

    4-Phenylbutyric acid protects against lipopolysaccharide-induced bone loss by modulating autophagy in osteoclasts.
    Biochem Pharmacol 2018 Feb 16. Epub 2018 Feb 16.
    Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea. Electronic address:
    4-Phenylbutyric acid (4-PBA) has been used clinically to treat urea cycle disorders and is known to be an inhibitor of endoplasmic reticulum (ER) stress. We hypothesized that 4-PBA attenuates inflammatory bone loss by inducing autophagy, a process that is frequently accompanied by ER stress. Micro computerized tomography analysis showed that 4-PBA attenuated LPS-induced bone loss in mice. Read More

    Effects of Cytochrome P450 Single Nucleotide Polymorphisms on Methadone Metabolism and Pharmacodynamics.
    Biochem Pharmacol 2018 Feb 16. Epub 2018 Feb 16.
    Department of Biomedical Sciences, Toxicology Research Cluster, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, 25755-9310, USA. Electronic address:
    Methadone is a synthetic, long-acting opioid with a single chiral center forming two enantiomers, (R)-methadone and (S)-methadone, each having specific pharmacological actions. Concentrations of (R)- and (S)-methadone above therapeutic levels have the ability to cause serious, life-threatening, and fatal side effects. This toxicity can be due in part to the pharmacogenetics of an individual, which influences the pharmacokinetic and pharmacodynamic properties of the drug. Read More

    BMP-2 induces angiogenesis by provoking integrin α6 expression in human endothelial progenitor cells.
    Biochem Pharmacol 2018 Feb 16. Epub 2018 Feb 16.
    Department of Medicine, Mackay Medical College, New Taipei City, Taiwan; Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:
    Bone morphogenetic proteins-2 (BMP-2) is a multifunctional cytokine, capable of governing several cellular functions, including proliferation, motility, differentiation, and angiogenesis. Circulating endothelial progenitor cells (EPCs) have been shown to facilitate tissue repair, postnatal neovascularization, and tumor associated angiogenesis. Nevertheless, the impact of BMP-2 on angiogenesis of human EPCs has largely remained a mystery. Read More

    Aldose reductase inhibitor, fidarestat prevents doxorubicin-induced endothelial cell death and dysfunction.
    Biochem Pharmacol 2018 Feb 16. Epub 2018 Feb 16.
    Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA. Electronic address:
    Despite doxorubicin (Dox) being one of the most widely used chemotherapy agents for breast, blood and lung cancers, its use in colon cancer is limited due to increased drug resistance and severe cardiotoxic side effects that increase mortality associated with its use at high doses. Therefore, better adjuvant therapies are warranted to improve the chemotherapeutic efficacy and to decrease cardiotoxicity. We have recently shown that aldose reductase inhibitor, fidarestat, increases the Dox-induced colon cancer cell death and reduces cardiomyopathy. Read More

    The G Protein-Coupled Receptors deorphanization landscape.
    Biochem Pharmacol 2018 Feb 15. Epub 2018 Feb 15.
    Laboratory of Molecular Pharmacology, GIGA-Molecular Biology of Diseases, ULiège, Belgium; Laboratory of Medicinal Chemistry, CIRM-Drug target and Lead Discovery, ULiège, Belgium. Electronic address:
    G protein-coupled receptors (GPCRs) are usually highlighted as being both the largest family of membrane proteins and the most productive source of drug targets. However, most of the GPCRs are understudied and hence cannot be used immediately for innovative therapeutic strategies. Besides, there are still around 100 orphan receptors, with no described endogenous ligand and no clearly defined function. Read More

    Extracellular loops 2 and 3 of the calcitonin receptor selectively modify agonist binding and efficacy.
    Biochem Pharmacol 2018 Feb 15. Epub 2018 Feb 15.
    Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Victoria, Australia. Electronic address:
    Class B peptide hormone GPCRs are targets for the treatment of major chronic disease. Peptide ligands of these receptors display biased agonism and this may provide future therapeutic advantage. Recent active structures of the calcitonin (CT) and glucagon-like peptide-1 (GLP-1) receptors reveal distinct engagement of peptides with extracellular loops (ECLs) 2 and 3, and mutagenesis of the GLP-1R has implicated these loops in dynamics of receptor activation. Read More

    Delineation of the functional properties and the mechanism of action of AA29504, an allosteric agonist and positive allosteric modulator of GABAreceptors.
    Biochem Pharmacol 2018 Feb 15. Epub 2018 Feb 15.
    Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark. Electronic address:
    The retigabine analog 2-amino-4-(2,4,6-trimethylbenzylamino)-phenyl]-carbamic acid ethyl ester (AA29504) is a positive allosteric modulator (PAM) of γ-aminobutyric acidreceptors (GABARs), and the modulator has been used in ex vivo/in vivo studies to probe the physiological roles of native δ-containing GABARs. In this study, the functional properties and mode of action of AA29504 were investigated at human GABARs expressed in Xenopus oocytes by two-electrode voltage clamp electrophysiology. AA29504 was found to be an allosteric GABAR agonist displaying low intrinsic activities at 3-30 μM. Read More

    Natural small molecule bigelovin suppresses orthotopic colorectal tumor growth and inhibits colorectal cancer metastasis via IL6/ STAT3 pathway.
    Biochem Pharmacol 2018 Feb 15. Epub 2018 Feb 15.
    Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong. Electronic address:
    Bigelovin, a sesquiterpene lactone, has been demonstrated to induce apoptosis, inhibit inflammation and angiogenesis in vitro, but its potential anti-metastatic activity remains unclear. In the present study, two colon cancer mouse models, orthotopic tumor allografts and experimental metastatic models were utilized to investigate the progression and metastatic spread of colorectal cancer after bigelovin treatments. Results showed that bigelovin (intravenous injection; 0. Read More

    Antihypertensive potential of linalool and linalool complexed with β-cyclodextrin: effects of subchronic treatment on blood pressure and vascular reactivity.
    Biochem Pharmacol 2018 Feb 15. Epub 2018 Feb 15.
    Laboratory of Cardiovascular Physiology and Pharmacology, Federal University of Bahia, Salvador, Bahia, Brazil.. Electronic address:
    Linalool (LIN) is a monoterpene alcohol present in some aromatic medicinal plants with biological activities that can impact cardiovascular diseases. This chemical class is highly volatile and β-cyclodextrin (β-CD) has been employed to improve the pharmacological properties of monoterpenes. Thus, the aim of this study was to evaluate the cardiovascular effects of LIN free focusing on the antihypertensive properties of this monoterpene and to study whether LIN, complexed in β-cyclodextrin (LIN-βCD) is able to improve the pharmacological activity of LIN. Read More

    Zoledronate modulates intracellular vesicle trafficking in mast cells via disturbing the interaction of myosinVa/Rab3a and sytaxin4/VAMP7.
    Biochem Pharmacol 2018 Feb 15. Epub 2018 Feb 15.
    Department of Pharmacology, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
    Nitrogen-containing bisphosphonates (NBPs) have been widely used as bone anti-resorptive drugs for the treatment of osteoclast-dependent bone disorders. Zoledronate is currently the most potent NBP, and has potential as an inhibitor of farnesyl pyrophosphate synthase. The present study was undertaken to elucidate the possible effects of zoledronate on FcεRI-dependent mast cell activity in vitro, which is essential for in maintaining homeostasis of the gastrointestinal mucosa. Read More

    Stimulation of TRPV1 channels activates the AP-1 transcription factor.
    Biochem Pharmacol 2018 Feb 13. Epub 2018 Feb 13.
    Department of Medical Biochemistry and Molecular Biology, Saarland University Medical Faculty, D-66421 Homburg, Germany. Electronic address:
    Transient receptor potential vanilloid 1 (TRPV1) channels were originally described as the receptors of capsaicin, the main constituent of hot chili pepper. The biological functions of TRPV1 channels include pain sensation and inflammatory thermal hyperalgesia. Here, we show that stimulation of HEK293 cells expressing TRPV1 channels (H2C1 cells) with capsaicin or the TRPV1 ligand resiniferatoxin activated transcription mediated by the transcription factor AP-1. Read More

    The macrophage heme-heme oxygenase-1 system and its role in inflammation.
    Biochem Pharmacol 2018 Feb 13. Epub 2018 Feb 13.
    Institute for Transfusion Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Electronic address:
    Heme oxygenase (HO)-1, the inducible isoform of the heme-degrading enzyme HO, plays a critical role in inflammation and iron homeostasis. Regulatory functions of HO-1 are mediated via the catalytic breakdown of heme, which is an iron-containing tetrapyrrole complex with potential pro-oxidant and pro-inflammatory effects. The HO reaction produces the antioxidant and anti-inflammatory compounds carbon monoxide (CO) and biliverdin, subsequently converted into bilirubin, along with iron, which is reutilized for erythropoiesis. Read More

    The role of free-fatty acid receptor-4 (FFA4) in human cancers and cancer cell lines.
    Biochem Pharmacol 2018 Feb 13. Epub 2018 Feb 13.
    Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA, 30341, United States. Electronic address:
    A dietary influence on cancer progression has been evident for many decades, and dietary fatty acids, particularly long chain mono- and polyunsaturated fatty acids, have been shown to play significant roles in influencing growth of a variety of human cancers. The discovery of the family of cell-surface free-fatty acid receptors, which include the long-chain fatty acid receptors FFA1 and FFA4, suggest that many of the effects of dietary fats could be receptor-mediated. FFA4 is ubiquitously expressed and has recently been shown to modulate a variety of important anti-inflammatory and metabolic processes. Read More

    Evolving mechanisms of vascular smooth muscle contraction highlight key targets in vascular disease.
    Biochem Pharmacol 2018 Feb 13. Epub 2018 Feb 13.
    Vascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA. Electronic address:
    Vascular smooth muscle (VSM) plays an important role in the regulation of vascular function. Identifying the mechanisms of VSM contraction has been a major research goal in order to determine the causes of vascular dysfunction and exaggerated vasoconstriction in vascular disease. Major discoveries over several decades have helped to better understand the mechanisms of VSM contraction. Read More

    Salmeterol, Agonist of β2-Aderenergic Receptor, Prevents Systemic Inflammation via Inhibiting NLRP3 Inflammasome.
    Biochem Pharmacol 2018 Feb 12. Epub 2018 Feb 12.
    Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 818 Tianyuan East Road, Nanjing, Jiangsu 211166, China; Department of Pharmacology, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, Jiangsu 210023, China. Electronic address:
    β2-aderenergic receptor (β2AR) agonist, Salmeterol exhibits anti-inflammatory activities. However, the inhibitory effects of Salmeterol on inflammasome activation are elusive and the underlying mechanisms need to be explored. In this study, we established inflammatory model in primary bone marrow-derived macrophages (BMDM) from C57BL/6J mice and β-arrestin2 knockout (β-arrestin2) mice in vitro. Read More

    Autophagy inducers in cancer.
    Biochem Pharmacol 2018 Feb 10. Epub 2018 Feb 10.
    Institute of Food Sciences, National Research Council, 83100 Avellino, Italy. Electronic address:
    Autophagy is a complex, physiological process devoted to degrade and recycle cellular components. Proteins and organelles are first phagocytized by autophagosomes, then digested in lysosomes, and finally recycled to be utilized again during cellular metabolism. Moreover, autophagy holds an important role in the physiopathology of several diseases. Read More

    Stress-induced cellular responses in immunogenic cell death: Implications for cancer immunotherapy.
    Biochem Pharmacol 2018 Feb 10. Epub 2018 Feb 10.
    College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea. Electronic address:
    Cancer is evading the host's defense mechanisms leading to avoidance of immune destruction. During tumor progression, immune-evading cancer cells arise due to selective pressure from the hypoxic and nutrient-deprived microenvironment. Thus, therapies aiming at re-establishing immune destruction of pathological cells constitute innovating anti-cancer strategies. Read More

    Angiotensin 1-7 ameliorates 6-hydroxydopamine lesions in hemiparkinsonian rats through activation of MAS receptor/PI3K/Akt/BDNF pathway and inhibition of angiotensin II type-1 receptor/NF-κB axis.
    Biochem Pharmacol 2018 Feb 8. Epub 2018 Feb 8.
    Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Κasr El-Aini Str., 11562, Cairo, Egypt.
    MAS receptor (MASR), expressed in several brain areas, conferred neuroprotection against neurodegenerative disorders when activated by angiotensin (Ang) 1-7; however, its role in Parkinson's disease (PD) remains elusive. Intra-striatal post-administration of Ang1-7, using a 6-hydroxydopamine (OHDA) PD model, improved motor performance and muscle coordination. On the molecular level, Ang1-7 upregulated the striatal expression of MASR and caused upsurge in its downstream targets (p-PI3K/p-Akt/p-CREB/BDNF) to phosphorylate TrKB, which in a positive feedback upregulates MASR. Read More

    Anti-inflammatory actions of Caesalpinin M2 in experimental colitis as a selective glucocoricoid receptor modulator.
    Biochem Pharmacol 2018 Feb 8;150:150-159. Epub 2018 Feb 8.
    State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China. Electronic address:
    Although repression of inflammatory gene expression makes glucocorticoids (GCs) powerful anti-inflammatory agents, side effects limit usage and drive the search for improved glucocorticoid receptor (GR) ligands. It has been postulated that the anti-inflammatory effects of GCs are primarily mediated by GR's activity in transrepressing major inflammation pathways such as NF-κB pathway, whereas their side effects are mostly mediated by GR's transactivation. In this study, we found that Caesalpinin M2 (C-M2), a cassane furanoditerpene isolated from a Chinese medical plant, exerts an anti-inflammatory potential both in vitro and in vivo. Read More

    Leptin induces SIRT1 expression through activation of NF-E2-related factor 2: Implications for obesity-associated colon carcinogenesis.
    Biochem Pharmacol 2018 Feb 7. Epub 2018 Feb 7.
    Tumor Microenvironment Global Core Research Center, Seoul National University, Seoul 08826, South Korea; Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, South Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Sciences and Technology, Seoul National University, Seoul 08826, South Korea; Cancer Research Institute, Seoul National University, Seoul 08826, South Korea. Electronic address:
    Leptin, a representative adipokine secreted from the white adipose tissue, is considered as a potential linker between obesity and cancer. SIRT1 is an NAD-dependent histone/protein deacetylase speculated to function as an oncogene. In the present study, we found that leptin signaling-defective ob/ob and db/db mice had lower colonic expression of SIRT1 compared with leptin signaling-intact C57BL/6J mice, implying that leptin signaling is crucial for SIRT1 expression in vivo. Read More

    Extracellular vesicles: A new therapeutic strategy for joint conditions.
    Biochem Pharmacol 2018 Feb 7. Epub 2018 Feb 7.
    Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, 46100 Burjasot, Valencia, Spain. Electronic address:
    Extracellular vesicles (EVs) are attracting increasing interest since they might represent a more convenient therapeutic tool with respect to their cells of origin. In the last years much time and effort have been expended to determine the biological properties of EVs from mesenchymal stem cells (MSCs) and other sources. The immunoregulatory, anti-inflammatory and regenerative properties of MSC EVs have been demonstrated in in vitro studies and animal models of rheumatoid arthritis or osteoarthritis. Read More

    Adenosine metabolism, immunity and joint health.
    Biochem Pharmacol 2018 Feb 7. Epub 2018 Feb 7.
    Department of Medicine, New York University, NY 10016, USA. Electronic address:
    The purine nucleoside adenosine is a present in most body fluids where it regulates a wide variety of physiologic and pharmacologic processes. Adenosine mediates its effects through activating 4 G protein-coupled receptors expressed on the cell membrane: A1, A2A, A2B, and A3. The adenosine receptors are widely distributed in the body, and tissues with high expression include immune tissues, cartilage, bone, heart, and brain. Read More

    Efflux inhibition by IWR-1-endo confers sensitivity to doxorubicin effects in osteosarcoma cells.
    Biochem Pharmacol 2018 Feb 8;150:141-149. Epub 2018 Feb 8.
    Mayo Clinic College of Medicine, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA; Mayo Clinic College of Medicine, Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA; Mayo Clinic College of Medicine, Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
    Osteosarcoma is the most common bone tumor that affects children and young adults. Despite advances in the use of combination chemotherapy regimens, response to neoadjuvant chemotherapy in osteosarcoma remains a key determinant of patient outcome. Recently, highly potent small molecule inhibitors of canonical Wnt signaling through the poly(ADP-ribose) polymerase (PARP)-family enzymes, tankyrases 1 & 2 (Tnks1/2), have been considered as possible chemotherapy sensitizing agents. Read More

    A novel combination of astilbin and low-dose methotrexate respectively targeting AAR and its ligand adenosine for the treatment of collagen-induced arthritis.
    Biochem Pharmacol 2018 Feb 2. Epub 2018 Feb 2.
    State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210023, China. Electronic address:
    Methotrexate (MTX) is widely used for rheumatoid arthritis (RA) treatment with frequently serious adverse effects. Therefore, combination of low-dose MTX with other drugs is often used in clinic. In this study, we investigated the improvement of astilbin and low-dose MTX combination on collagen-induced arthritis in DBA/1J mice. Read More

    Regulatory-Accepted Drug Development Tools Are Needed to Accelerate Innovative CNS Disease Treatments.
    Biochem Pharmacol 2018 Jan 30. Epub 2018 Jan 30.
    Critical Path for Parkinson's, Crititcal Path Institute, United States.
    Central Nervous System (CNS) diseases represent one of the most challenging therapeutic areas for successful drug approvals. Developing quantitative biomarkers as Drug Development Tools (DDTs) can catalyze the path to innovative treatments, and improve the chances of drug approvals. Drug development and healthcare management requires sensitive, reliable, validated, and regulatory accepted biomarkers and endpoints. Read More

    Investigations on the role of hemoglobin in sulfide metabolism by intact human red blood cells.
    Biochem Pharmacol 2018 Jan 31. Epub 2018 Jan 31.
    Cardiovascular Research Laboratory, Division of Cardiology, Pulmunology and Vascular Medicine, Medical Faculty, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany; CARID, Cardiovascular Research Institute Düsseldorf, Medical Faculty, Heinrich-Heine-University, Moorensstrasse 5, 40225 Düsseldorf, Germany. Electronic address:
    In addition to their role as oxygen transporters, red blood cells (RBCs) contribute to cardiovascular homeostasis by regulating nitric oxide (NO) metabolism via interaction of hemoglobin (Hb) with nitrite and NO itself. RBCs were proposed to also participate in sulfide metabolism. Although Hb is known to react with sulfide, sulfide metabolism by intact RBCs has not been characterized so far. Read More

    The tumor-suppressor cholesterol metabolite, dendrogenin A, is a new class of LXR modulator activating lethal autophagy in cancers.
    Biochem Pharmacol 2018 Feb 1. Epub 2018 Feb 1.
    Team "Cholesterol Metabolism and Therapeutic Innovations", Cancer Research Center of Toulouse, UMR 1037 INSERM-University of Toulouse, Toulouse, France; Cancer Research Center of Toulouse, UMR 1037 INSERM-University of Toulouse, Toulouse, France. Electronic address:
    Dendrogenin A (DDA) is a mammalian cholesterol metabolite recently identified that displays tumor suppressor properties. The discovery of DDA has revealed the existence in mammals of a new metabolic branch in the cholesterol pathway centered on 5,6α-epoxycholesterol and bridging cholesterol metabolism with histamine metabolism. Metabolic studies showed a drop in DDA levels in cancer cells and tumors compared to normal cells, suggesting a link between DDA metabolism deregulation and oncogenesis. Read More

    Regulation and function of apoptosis signal-regulating kinase 1 in rheumatoid arthritis.
    Biochem Pharmacol 2018 Feb 6. Epub 2018 Feb 6.
    UCSD School of Medicine, La Jolla, California, United States. Electronic address:
    Despite improved therapy, rheumatoid arthritis (RA) remains an unmet medical need. Previous efforts to validate therapeutic targets in the mitogen-activated protein kinase (MAPK) family have had minimal success. Therefore, we evaluated the potential for targeting an upstream MAPK, namely apoptosis signal-regulating kinase 1 (ASK1), as an alternative approach. Read More

    The potentially conflicting cell autonomous and cell non-autonomous functions of autophagy in mediating tumor response to cancer therapy.
    Biochem Pharmacol 2018 Feb 3. Epub 2018 Feb 3.
    Department of Human and Molecular Genetics, Virginia Commonwealth University, United States.
    Autophagy, a virtually uniform response to external stress such as that induced by chemotherapy and radiation, is generally considered to be cytoprotective in function, providing a foundation for multiple clinical trials designed to enhance therapeutic response via autophagy inhibition. However, this cell autonomous response can also be cytotoxic or nonprotective, with the consequence that autophagy inhibition would be counterproductive or ineffective, respectively. The non-cell autonomous function of autophagy remains quite controversial, with evidence both for and against autophagy-mediated activation of the immune system. Read More

    Promise and challenges for direct small molecule AMPK activators.
    Biochem Pharmacol 2018 Feb 3. Epub 2018 Feb 3.
    INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, France. Electronic address:
    AMP-activated protein kinase (AMPK) is an evolutionary conserved and ubiquitously expressed serine/threonine kinase playing a central role in the coordination of energy homeostasis. Based on the beneficial outcomes of its activation on metabolism, AMPK has emerged as an attractive target for the treatment of metabolic diseases. Identification of novel downstream targets of AMPK beyond the regulation of energy metabolism has renewed considerable attention in exploiting AMPK signaling for novel therapeutic targeting strategies including treatment of cancer and inflammatory diseases. Read More

    Ribociclib, a Cdk4/Cdk6 kinase inhibitor, enhances glucocorticoid sensitivity in B-acute lymphoblastic leukemia (B-All).
    Biochem Pharmacol 2018 Feb 3. Epub 2018 Feb 3.
    Department of Woman's and Child's Heath, Oncohematology Lab, University of Padova, Italy. Electronic address:
    Dysregulation of the cyclin D1-CDK4/CDK6 complex is frequently observed in almost all human cancer and contributes to aberrant cell proliferation and consequent tumorigenesis. Although many reports described the importance of CDK4/CDK6 in different set of human tumors, only few studies have been performed on leukemia. By gene expression analysis performed in a cohort of childhood patients affected by B-acute lymphoblastic leukemia (B-ALL) we found that both CDK4 and CDK6 are highly expressed. Read More

    PBA2 exhibits potent anti-tumor activity via suppression of VEGFR2 mediated-cell proliferation and angiogenesis.
    Biochem Pharmacol 2018 Feb 3;150:131-140. Epub 2018 Feb 3.
    State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Esophageal Cancer Institute, Sun Yat-sen University Cancer Center, Guangzhou 510060, China. Electronic address:
    VEGFR2 (vascular endothelial growth factor receptor 2) is the main trigger of VEGF-mediated angiogenic signal and targeting VEGFR2 pathway to inhibit tumor angiogenesis represents a promising strategy for cancer therapy. We elucidated that a novel compound, PBA2 exhibited potent anti-tumor effects both in vitro and in vivo with limited toxicity. ELISA assay revealed that PBA2 had a strong suppressive activity against VEGFR2 related to angiogenesis. Read More

    Presence and inter-individual variability of carboxylesterases (CES1 and CES2) in human lung.
    Biochem Pharmacol 2018 Jan 29;150:64-71. Epub 2018 Jan 29.
    Institute of Agricultural Biology and Biotechnology, National Research Council, via Moruzzi 1, 56124 Pisa, Italy. Electronic address:
    Lungs are pharmacologically active organs and the pulmonary drug metabolism is of interest for inhaled drugs design. Carboxylesterases (CESs) are enzymes catalyzing the hydrolysis of many structurally different ester, amide and carbamate chemicals, including prodrugs. For the first time, the presence, kinetics, inhibition and inter-individual variations of the major liver CES isozymes (CES1 and CES2) were investigated in cytosol and microsomes of human lungs from 20 individuals using 4-nitrophenyl acetate (pNPA), 4-methylumbelliferyl acetate (4-MUA), and fluorescein diacetate (FD) as substrates the rates of hydrolysis (V) for pNPA and 4-MUA, unlike FD, were double in microsomes than in cytosol. Read More

    The dichotomous role of HS in cancer cell biology? Déjà vu all over again.
    Biochem Pharmacol 2018 Feb 2. Epub 2018 Feb 2.
    Department of Molecular, Cellular and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, NY, USA. Electronic address:
    Nitric oxide (NO) a gaseous free radical is one of the ten smallest molecules found in nature, while hydrogen sulfide (HS) is a gas that bears the pungent smell of rotten eggs. Both are toxic yet they are gasotransmitters of physiological relevance. There appears to be an uncanny resemblance between the general actions of these two gasotransmitters in health and disease. Read More

    Activation of mitochondrial fusion provides a new treatment for mitochondria-related diseases.
    Biochem Pharmacol 2018 Jan 31;150:86-96. Epub 2018 Jan 31.
    Department of Biochemistry and Medical Chemistry, University of Pécs Medical School, Pécs, Hungary; Szentagothai Research Centre, University of Pécs, Pécs, Hungary; Nuclear-Mitochondrial Interactions Research Group, Hungarian Academy of Sciences, Budapest, Hungary. Electronic address:
    Mitochondria fragmentation destabilizes mitochondrial membranes, promotes oxidative stress and facilitates cell death, thereby contributing to the development and the progression of several mitochondria-related diseases. Accordingly, compounds that reverse mitochondrial fragmentation could have therapeutic potential in treating such diseases. BGP-15, a hydroxylamine derivative, prevents insulin resistance in humans and protects against several oxidative stress-related diseases in animal models. Read More

    The E3 ubiquitin ligases HOIP and cIAP1 are recruited to the TNFR2 signaling complex and mediate TNFR2-induced canonical NF-κB signaling.
    Biochem Pharmacol 2018 Jan 31. Epub 2018 Jan 31.
    Center for Inflammation Research, VIB, Unit of Molecular Signal Transduction in Inflammation, Technologiepark 927, Zwijnaarde, Ghent 9052, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, Zwijnaarde, Ghent 9052, Belgium. Electronic address:
    Tumor Necrosis Factor (TNF) is a proinflammatory cytokine that elicits its action by binding to two cell surface TNF receptors (TNFR), TNFR1 and TNFR2, which are expressed by many different cell types. Stimulation of TNFR1 activates canonical NF-κB signaling, leading to the NF-κB dependent expression of a large number of genes. Canonical NF-κB signaling requires the assembly of a TNFR1 signaling complex at the cell membrane, whose formation is regulated by different protein ubiquitination events. Read More

    Regulation of Kv4.3 and hERG potassium channels by KChIP2 isoforms and DPP6 and response to the dual Kchannel activator NS3623.
    Biochem Pharmacol 2018 Jan 31;150:120-130. Epub 2018 Jan 31.
    School of Physiology, Pharmacology and Neuroscience, Faculty of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK. Electronic address:
    Transient outward potassium current (I) contributes to early repolarization of many mammalian cardiac action potentials, including human, whilst the rapid delayed rectifier Kcurrent (I) contributes to later repolarization. Fast Ichannels can be produced from the Shal family KCNDE gene product Kv4.3s, although accessory subunits including KChIP2. Read More

    Human GIP(3-30)NHinhibits G protein-dependent as well as G protein-independent signaling and is selective for the GIP receptor with high-affinity binding to primate but not rodent GIP receptors.
    Biochem Pharmacol 2018 Jan 31;150:97-107. Epub 2018 Jan 31.
    Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address:
    GIP(3-30)NHis a high affinity antagonist of the GIP receptor (GIPR) in humans inhibiting insulin secretion via G protein-dependent pathways. However, its ability to inhibit G protein-independent signaling is unknown. Here we determine its action on arrestin-recruitment and receptor internalization in recombinant cells. Read More

    Regulation on SIRT1-PGC-1α/Nrf2 pathway together with selective inhibition of aldose reductase makes compound hr5F a potential agent for the treatment of diabetic complications.
    Biochem Pharmacol 2018 Jan 29;150:54-63. Epub 2018 Jan 29.
    College of Pharmacy, Jinan University, Guangzhou 510632, PR China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632, PR China. Electronic address:
    (R,E)-N-(3-(2-acetamido-3-(benzyloxy) propanamido)propyl)-2-cyano-3-(4-hydroxy phenyl)acrylamide (hr5F) was design-synthesized based on bioactivity focus strategy as a potential agent to treat diabetic complicates. With in vitro enzyme assay, it is confirmed that hr5F is an effective ALR2 inhibitor with ICvalue of 2.60 ± 0. Read More

    Melanoma antigen-D2 controls cell cycle progression and modulates the DNA damage response.
    Biochem Pharmacol 2018 Feb 1. Epub 2018 Feb 1.
    GIGA-Molecular Biology of Diseases, Virology and Immunology Unit, University of Liège, Quartier de l'Hôpital, 11 Allée de l'Hôpital, Building B34, 4000 Liège, Belgium. Electronic address:
    Overexpression of the ubiquitous type II melanoma antigen-D2 (MAGED2) in numerous types of cancer suggests that this protein contributes to carcinogenesis, a well-documented characteristic of other MAGE proteins. Modification of MAGED2 intracellular localization during cell cycle phases and following treatment with camptothecin (CPT) and phosphorylation by ATM/ATR following ionizing irradiation led us to investigate the molecular functions of MAGED2 in the cellular response to DNA damage. Cell cycle regulators, cell cycle progression, and bromodeoxyuridine (BrdU) incorporation were compared between MAGED2-sufficient and -depleted U2OS cells following exposure to CPT. Read More

    Pharmacological inhibitory profile of TAK-828F, a potent and selective orally available RORγt inverse agonist.
    Biochem Pharmacol 2018 Jan 30;150:35-45. Epub 2018 Jan 30.
    Immunology Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa, Japan. Electronic address:
    Retinoic acid-related orphan receptor γt (RORγt) is a key master regulator of the differentiation and activation of IL-17 producing CD4Th17, CD8Tc17 and IL-17/IFN-γ co-producing cells (Th1/17 cells). These cells play critical roles in the pathogenesis of autoimmune diseases such as inflammatory bowel disease and multiple sclerosis. Thus, RORγt is an attractive target for the treatment of these diseases. Read More

    The imidazoline Ireceptor agonist 2-BFI attenuates hypersensitivity and spinal neuroinflammation in a rat model of neuropathic pain.
    Biochem Pharmacol 2018 Jan 29. Epub 2018 Jan 29.
    Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, The State University of New York, University at Buffalo, Buffalo, NY, USA. Electronic address:
    Chronic pain is a large, unmet public health problem. Recent studies have demonstrated the importance of neuroinflammation in the establishment and maintenance of chronic pain. However, pharmacotherapies that reduce neuroinflammation have not been successfully developed to treat chronic pain thus far. Read More

    Dihydroartemisinin suppresses STAT3 signaling and Mcl-1 and Survivin expression to potentiate ABT-263-induced apoptosis in Non-small Cell Lung Cancer cells harboring EGFR or RAS mutation.
    Biochem Pharmacol 2018 Jan 30;150:72-85. Epub 2018 Jan 30.
    National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi'an 710119, Shaanxi, China. Electronic address:
    Non-small cell lung cancer (NSCLC) is the most common malignancy worldwide. A significant fraction of NSCLC carries activating mutations in epidermal growth factor receptor (EGFR) or RAS oncogene. Dihydroartemisinin (DHA) is a semisynthetic derivative of the herbal antimalarial drug artemisinin that has been recently reported to exhibit anti-cancer activity. Read More

    Is there a role of HS in mediating health span benefits of caloric restriction?
    Biochem Pharmacol 2018 Jan 19. Epub 2018 Jan 19.
    Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Neurobiology Programme, Life Sciences Institute, National University of Singapore, Singapore.
    Caloric restriction (CR) is a dietary regimen that aims to reduce the intake of total calories while maintaining adequate supply of key nutrients so as to avoid malnutrition. CR is one of only a small number of interventions that show promising outcomes on health span and lifespan across different species. There is growing interest in the development of compounds that might replicate CR-related benefits without actually restricting food intake. Read More

    Glutazumab, a novel long-lasting GLP-1/anti-GLP-1R antibody fusion protein, exerts anti-diabetic effects through targeting dual receptor binding sites.
    Biochem Pharmacol 2018 Jan 26;150:46-53. Epub 2018 Jan 26.
    State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Xiannongtan Street, Beijing 100050, China. Electronic address:
    Aims: Glucagon like-peptide-1 (GLP-1)-based drugs have been proposed as mono- or combined therapy for type 2 diabetes mellitus. Thus we characterized a novel antibody fusion protein engineered by linking the human GLP-1 derivative to a humanized GLP-1 receptor (GLP-1R) antibody via a peptide linker.

    Materials And Methods: Glutazumab was characterized by receptor binding and reporter activation assays, and its specificity was investigated with the aid of the cognate receptor antagonist exendin (9-39) and antibody Ab1. Read More

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