26,540 results match your criteria Biochemical Pharmacology[Journal]


Comprehensive study of thiopurine methyltransferase genotype, phenotype, and genotype-phenotype discrepancies in Sweden.

Biochem Pharmacol 2019 Apr 18. Epub 2019 Apr 18.

Division of Drug Research, Department of Medical and Health Sciences, Linköping University, SE-581 83 Linköping, Sweden. Electronic address:

Thiopurines are widely used in the treatment of leukemia and inflammatory bowel diseases. Thiopurine metabolism varies among individuals because of differences in the polymorphic enzyme thiopurine methyltransferase (TPMT, EC 2.1. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.04.020DOI Listing

Telmisartan and/or Chlorogenic Acid Attenuates Fructose-Induced Non-Alcoholic Fatty Liver Disease in Rats: Implications of Cross-Talk between Angiotensin, the Sphingosine Kinase/Sphingoine-1-Phosphate Pathway, and TLR4 Receptors.

Biochem Pharmacol 2019 Apr 17. Epub 2019 Apr 17.

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11459, Saudi Arabia.

Renin-angiotensin-aldosterone system (RAS) has been implicated in non-alcoholic fatty liver disease (NAFLD); the most common cause of chronic liver diseases. There is accumulating evidence that altered TLR4 and Sphingosine kinase 1(SphK1)/sphingosine1phosphate (S1P) signaling pathways are key players in the pathogenesis of NAFLD. Cross talk of the sphingosine signaling pathway, toll-4 (TLR4) receptors ,and angiotensin II was reported in various tissues. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.04.018DOI Listing

A novel bromodomain inhibitor, CPI-203, serves as an HIV-1 latency-reversing agent by activating positive transcription elongation factor b.

Biochem Pharmacol 2019 Apr 13;164:237-251. Epub 2019 Apr 13.

Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China. Electronic address:

The persistence of latent human immunodeficiency virus type 1 (HIV-1) reservoirs remains a major hurdle for HIV-1 eradication. The "shock and kill" strategy relies on the drug-mediated reversion of HIV-1 latency and the subsequent death of HIV-producing cells. Unfortunately, none of the agents currently in use possess a sufficient potency to reactivate latent virus or eliminate the latent HIV-1 reservoir in vivo. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00062952193014
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http://dx.doi.org/10.1016/j.bcp.2019.04.005DOI Listing
April 2019
2 Reads

The in vitro and in vivo depigmenting activity of Coenzyme Q10 through the down-regulation of α-MSH signaling pathways and induction of Nrf2/ARE-mediated antioxidant genes in UVA-irradiated skin keratinocytes.

Biochem Pharmacol 2019 Apr 13. Epub 2019 Apr 13.

Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan. Electronic address:

Coenzyme CoQ10 (CoQ10), a ubiquinone compound, has been reported to inhibit tyrosinase activity and melanin production in melanoma B16F10 cells. However, the molecular mechanism underlying this inhibitory effect is poorly understood. In this paper we aimed to investigate the molecular mechanisms involved in the anti-melanogenic activity of CoQ10 (1-2 μM) in UVA (5 J/cm)-irradiated keratinocyte HaCaT cells and α-MSH stimulated B16-F10 cells. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.04.015DOI Listing
April 2019
5.009 Impact Factor

Pharmacological inhibition of β-catenin prevents EndMT in vitro and vascular remodeling in vivo resulting from endothelial Akt1 suppression.

Biochem Pharmacol 2019 Apr 13;164:205-215. Epub 2019 Apr 13.

Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA 30912, United States; Department of Medicine, Vascular Biology Center and Cancer Center, Augusta University, Augusta, GA 30912, United States. Electronic address:

Endothelial to mesenchymal transition (EndMT), where endothelial cells acquire mesenchymal characteristics has been implicated in several cardiopulmonary, vascular and fibrotic diseases. The most commonly studied molecular mechanisms involved in EndMT include TGFβ, Notch, interleukin, and interferon-γ signaling. As of today, the contributions of Akt1, an important mediator of TGFβ signaling and a key regulator of endothelial barrier function to EndMT remains unclear. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.04.016DOI Listing

Berberine stimulates fibroblast growth factor 21 by modulating the molecular clock component brain and muscle Arnt-like 1 in brown adipose tissue.

Biochem Pharmacol 2019 Apr 13;164:165-176. Epub 2019 Apr 13.

Laboratory of Medicinal Resources, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650, Japan.

Fibroblast growth factor 21 (FGF21), a member of the FGF subfamily that acts through the FGF receptor 1 with the co-receptor β-Klotho, functions as an important metabolic regulator of peripheral glucose tolerance and lipid homeostasis in an endocrine or autocrine and/or paracrine manner. Previous studies showed that FGF21 ameliorated and prevented the development of metabolic disorders, such as obesity and diabetes mellitus. In the present study, we demonstrated that berberine, a naturally occurring compound, stimulated FGF21 expression in brown adipose tissue (BAT). Read More

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http://dx.doi.org/10.1016/j.bcp.2019.04.017DOI Listing

Effects of 17β-estradiol on colorectal cancer development after azoxymethane/dextran sulfate sodium treatment of ovariectomized mice.

Biochem Pharmacol 2019 Apr 11;164:139-151. Epub 2019 Apr 11.

Tumor Microenvironment Global Core Research Center, Seoul National University College of Pharmacy, Seoul, South Korea.

Estrogen is known to have a protective effect in colorectal cancer (CRC) development. Previously, we reported the anti-inflammatory and antitumorigenic effects of 17β-estradiol (E2) in azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated male mice. The aim of this study was to investigate whether ovariectomy in a female AOM/DSS mouse model increases colorectal tumorigenesis and whether tumorigenesis is reduced by estrogen supplementation after ovariectomy. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.04.011DOI Listing
April 2019
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Targeting hsp90 family members: A strategy to improve cancer cell death.

Biochem Pharmacol 2019 Apr 11;164:177-187. Epub 2019 Apr 11.

Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Belgium.

A crucial process in biology is the conversion of the genetic information into functional proteins that carry out the genetic program. However, a supplementary step is required to obtain functional proteins: the folding of the newly translated polypeptides into well-defined, three-dimensional conformations. Proteins chaperones are crucial for this final step in the readout of genetic information, which results in the formation of functional proteins. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.04.010DOI Listing
April 2019
1 Read

Therapeutic advances in arthritis diseases.

Biochem Pharmacol 2019 Apr 11. Epub 2019 Apr 11.

Laboratory of Rheumatology, GIGA Research, University and CHU of Liège, 4000 Liège, Belgium.

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http://dx.doi.org/10.1016/j.bcp.2019.04.014DOI Listing

Lactate-stimulated ethanol oxidation: Revisiting an old hypothesis.

Biochem Pharmacol 2019 Apr 11. Epub 2019 Apr 11.

Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM). Ciudad de México 04510, MEXICO. Electronic address:

Liver slices from starved rats and incubated without other substrates oxidized ethanol at a rate of 4.1 µmols • h • g. Addition of 10 mmols • L lactate increased this rate 2-fold. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.04.012DOI Listing
April 2019
2 Reads

Cytochrome P450 enzymes contribute to the metabolism of LSD to nor-LSD and 2-oxo-3-hydroxy-LSD: Implications for clinical LSD use.

Biochem Pharmacol 2019 Apr 11;164:129-138. Epub 2019 Apr 11.

Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.

In recent years, experimental research on lysergic acid diethylamide (LSD) in humans has gained new momentum. In humans, LSD is metabolized rapidly into several metabolites but knowledge of the involved metabolizing enzymes is limited. The aim of the current study was to identify the cytochrome P450 (CYP) isoforms involved in the metabolism of LSD to 6-norlysergic acid diethylamide (nor-LSD) and 2-oxo-3-hydroxy-LSD (O-H-LSD) in vitro, in order to evaluate potential effects of enzyme polymorphisms or prescription drugs on LSD pharmacokinetics. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.04.013DOI Listing
April 2019
1 Read

Anti-inflammatory functions of the CDC25 phosphatase inhibitor BN82002 via targeting AKT2.

Biochem Pharmacol 2019 Apr 10;164:216-227. Epub 2019 Apr 10.

Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea; Department of Biocosmetics, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address:

This study presents BN82002 as an anti-inflammatory drug candidate. It was found that BN82002 inhibited the production of nitric oxide (NO) and prostaglandin E (PGE) in RAW 264.7 cells and peritoneal macrophages that were activated by toll-like receptor (TLR) 4 ligand, lipopolysaccharide (LPS). Read More

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http://dx.doi.org/10.1016/j.bcp.2019.04.007DOI Listing

Advances in understanding the regulatory mechanism of cholesterol 7α-hydroxylase.

Biochem Pharmacol 2019 Apr 10;164:152-164. Epub 2019 Apr 10.

Key Laboratory of Biotechnology of Antibiotics, the National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. Electronic address:

The conversion of cholesterol to bile acids (BAs) contributes to the elimination of total cholesterol from the body. In addition, manipulating BA homeostasis by modulating cholesterol 7α-hydroxylase (CYP7A1) may affect the metabolic processing of cholesterol, exerting therapeutic effects on hypercholesterolemia and cardiovascular diseases. Multiple mechanisms (such as various nuclear receptors and regulatory factors) are involved in CYP7A1 modulation. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00062952193014
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http://dx.doi.org/10.1016/j.bcp.2019.04.008DOI Listing
April 2019
2 Reads

Risks and benefits of corticosteroids in arthritic diseases in the clinic.

Biochem Pharmacol 2019 Apr 9. Epub 2019 Apr 9.

Department of Biomolecular Medicine, Ghent University, Ghent, Belgium; Translational Nuclear Receptor Research, VIB Center for Medical Biotechnology, Ghent, Belgium. Electronic address:

Glucocorticoids (GCs) constitute a first line treatment for many autoimmune and inflammatory diseases. Due to their potent anti-inflammatory and immunosuppressive actions, GCs are added frequently to disease modifying antirheumatic drugs (DMARDs) in various arthritic diseases, such as rheumatoid arthritis. However, their prolonged administration or administration at high doses is associated with adverse effects that may be (quality of) life-threatening, including osteoporosis, metabolic, gastrointestinal and cardiovascular side effects. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00062952193014
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http://dx.doi.org/10.1016/j.bcp.2019.04.009DOI Listing
April 2019
7 Reads

Structure-based design and in vivo anti-arthritic activity evaluation of a potent dipeptidyl cyclopropyl nitrile inhibitor of cathepsin C.

Biochem Pharmacol 2019 Apr 9. Epub 2019 Apr 9.

Neuprozyme Therapeutics A/S, 2970 Hörsholm, Denmark.

Cathepsin C (CatC) is a dipeptidyl-exopeptidase which activates neutrophil serine protease precursors (elastase, proteinase 3, cathepsin G and NSP4) by removing their N-terminal propeptide in bone marrow cells at the promyelocytic stage of neutrophil differentiation. The resulting active proteases are implicated in chronic inflammatory and autoimmune diseases. Hence, inhibition of CatC represents a therapeutic strategy to suppress excessive protease activities in various neutrophil mediated diseases. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.04.006DOI Listing

Neuro-hormonal mechanisms underlying changes in reward related behaviors following weight loss surgery: Potential pharmacological targets.

Biochem Pharmacol 2019 Apr 4;164:106-114. Epub 2019 Apr 4.

Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, PA, United States.

Currently, the only available effective treatment option for obesity and its comorbidities is weight loss surgery (WLS). Long-term maintenance of weight loss after surgery cannot be explained by caloric restriction or malabsorption alone and has been attributed to unexplained changes in eating behavior. Whether these behavioral changes are related to altered taste or reward functions, or both, are subject to debate. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.04.004DOI Listing
April 2019
2 Reads

Uric acid treatment after stroke modulates the Krüppel-like factor 2-VEGF-A axis to protect brain endothelial cell functions: Impact of hypertension.

Biochem Pharmacol 2019 Apr 4;164:115-128. Epub 2019 Apr 4.

Departament de Farmacologia, de Terapèutica i de Toxicologia, Facultat de Medicina, Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain. Electronic address:

Uric acid (UA) is a promising protective treatment in ischaemic stroke, but the precise molecular targets underlying its in vivo beneficial actions remain unclear. High concentrations of UA inhibit angiogenesis of cultured endothelial cells via Krüppel-like factor 2 (KLF)-induced downregulation of vascular endothelial growth factor (VEGF), a pro-angiogenic mediator that is able to increase blood-brain barrier (BBB) permeability in acute stroke. Here, we investigated whether UA treatment after ischaemic stroke protects brain endothelial cell functions and modulates the KLF2-VEGF-A axis. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.04.002DOI Listing
April 2019
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Chemotherapeutic and antiangiogenic drugs beyond tumor progression in colon cancer: Evaluation of the effects of switched schedules and related pharmacodynamics.

Biochem Pharmacol 2019 Apr 3;164:94-105. Epub 2019 Apr 3.

Dipartimento di Medicina Clinica e Sperimentale, Università di Pisa, Via Savi 10, I-56126 Pisa, Italy. Electronic address:

The aim of the study was to evaluate the effects and the related pharmacological mechanisms of switched schedules of antiangiogenic and chemotherapeutic drugs beyond progression after a first-line treatment in a colorectal cancer preclinical model. In vivo studies were performed in nude mice subcutaneously transplanted with colon cancer cells. The treatments included drug combinations with a switch between chemotherapeutic (i. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.04.001DOI Listing
April 2019
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Keep recycling going: new approaches to reduce LDL-C.

Biochem Pharmacol 2019 Apr 3. Epub 2019 Apr 3.

Fox Chase Cancer Center, 333 Cotman Ave, Philadelphia, 19111, United States; Holy Family University, Frankford Ave, Philadelphia, 19114, United States. Electronic address:

Hypercholesterolemia represents a leading cause in the development of atherosclerotic plaques, increasing the risk for ACVS. It actually counts as a major cause of cardiovascular disease etiopathogenesis. The causes of hypercholesterolemia are multifactorial, spanning from genetic constitution, age, sex, to sedentary lifestyle and diets rich in sugars and lipids. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.04.003DOI Listing
April 2019
3 Reads

Distinct contribution of Rac1 expression in cardiomyocytes to anthracycline-induced cardiac injury.

Biochem Pharmacol 2019 Mar 29;164:82-93. Epub 2019 Mar 29.

Institute of Toxicology, Medical Faculty, Heinrich-Heine University Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany. Electronic address:

Cardiotoxicity is the dose limiting adverse effect of anthracycline-based anticancer therapy. Inhibitor studies point to Rac1 as therapeutic target to prevent anthracycline-induced cardiotoxicity. Yet, supporting genetic evidence is still missing and the pathophysiological relevance of different cardiac cell types is unclear. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.038DOI Listing
March 2019
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15-Deoxy-Δ-12, 14-prostaglandin J2 acts cooperatively with prednisolone to reduce TGF-β-induced pro-fibrotic pathways in human osteoarthritis fibroblasts.

Biochem Pharmacol 2019 Mar 29. Epub 2019 Mar 29.

Laboratory of Rheumatology, GIGA Research, University and CHU of Liège, 4000 Liège, Belgium. Electronic address:

Background/aims: Synovial fibrosis is a pathological process that is observed in several musculoskeletal disorders and characterized by the excessive deposition of extracellular matrix, as well as cell migration and proliferation. Despite the fact that glucocorticoids are widely employed in the treatment of rheumatic pathologies such as osteoarthritis (OA) and rheumatoid arthritis, the mechanisms by which glucocorticoids act in the joint and their impacts on pro-fibrotic pathways are still unclear.

Materials: Human OA synovial fibroblasts were obtained from knee and hip joints. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.039DOI Listing
March 2019
3 Reads

Human alcohol dehydrogenase 1 is an acceptor protein for polyADP-ribosylation.

Biochem Pharmacol 2019 Mar 29. Epub 2019 Mar 29.

Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan. Electronic address:

Alcohol dehydrogenase (ADH) is important for preventing alcohol toxicity and developmental disorders, and may be involved in other diseases including neurodegenerative diseases. We found that the major acceptor protein of polyADP-ribosylation in a model organism of neurodegeneration using a Drosophila melanogaster mutant lacking poly(ADP-ribose) glycohydrolase, was ADH. Thus we postulated that human ADH activity might be regulated by polyADP-ribosylation, a post-translational modification. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.037DOI Listing

New insights into exogenous surfactant as a carrier of pulmonary therapeutics.

Biochem Pharmacol 2019 Mar 27;164:64-73. Epub 2019 Mar 27.

Department of Medicine and Physiology & Pharmacology, Western University, London, Ontario, Canada. Electronic address:

As an organ system, the lung has unique advantages and disadvantages for localized drug delivery. Its direct contact with the external environment allows for the upper airways to be easily accessible to intrapulmonary delivery. However, its complex branching structure makes direct delivery to the peripheral airways challenging. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.036DOI Listing
March 2019
2 Reads

Targeting the autotaxin - Lysophosphatidic acid receptor axis in cardiovascular diseases.

Biochem Pharmacol 2019 Mar 27;164:74-81. Epub 2019 Mar 27.

Centre de Recherche du Centre Hospitalier Universitaire de Québec - Université Laval, Canada; Département de microbiologie, infectiologie et immunologie, Faculté de Médecine, Université Laval, Québec, QC G1V4G2, Canada. Electronic address:

Lysophosphatidic acid (LPA) is a well-characterized bioactive lipid mediator, which is involved in development, physiology, and pathological processes of the cardiovascular system. LPA can be produced both inside cells and in biological fluids. The majority of extracellularLPAis produced locally by the secreted lysophospholipase D, autotaxin (ATX), through its binding to various β integrins or heparin sulfate on cell surface and hydrolyzing various lysophospholipids. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.035DOI Listing
March 2019
6 Reads
5.009 Impact Factor

Marfan syndrome: A therapeutic challenge for long-term care.

Biochem Pharmacol 2019 Mar 27;164:53-63. Epub 2019 Mar 27.

INCCI HaerzZenter, Department of Cardiac Surgery, Luxembourg, Luxembourg.

Marfan syndrome (MFS) is an autosomal dominant genetic disorder caused by mutations in the fibrillin-1 gene. Acute aortic dissection is the leading cause of death in patients suffering from MFS and consequence of medial degeneration and aneurysm formation. In addition to its structural function in the formation of elastic fibers, fibrillin has a major role in keeping maintaining transforming growth factor β (TGF-β) in an inactive form. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.034DOI Listing
March 2019
3 Reads

Re-examining osteoarthritis therapy from a developmental biologist's perspective.

Biochem Pharmacol 2019 Mar 26. Epub 2019 Mar 26.

Lab 10, Department of Biological Sciences and Bio-engineering, IIT, Kanpur, India. Electronic address:

Osteoarthritis is the most prevalent musculoskeletal disorder and one for which there is no disease modifying therapy available at present. Our current understanding of the disease mechanism of osteoarthritis is limited owing to a lacuna of knowledge about the development and maintenance of articular cartilage that is affected during osteoarthritis. All current therapeutic strategies aim at countering inflammation which though mitigates pain but does not arrest the progressive degeneration of articular cartilage. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.020DOI Listing
March 2019
3 Reads

Adipokines: Linking metabolic syndrome, the immune system, and arthritic diseases.

Biochem Pharmacol 2019 Mar 22. Epub 2019 Mar 22.

SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Santiago University Clinical Hospital, Building C, Travesía da Choupana S/N, Santiago de Compostela 15706, Spain. Electronic address:

Metabolic syndrome (MetS) represents a cluster of metabolic and cardiovascular complications, including obesity and visceral adiposity, insulin resistance, dyslipidemia, hyperglycemia and hypertension, which directly increase the risk of cardiovascular diseases (CVD) and diabetes mellitus type 2 (DM2). Patients with arthritic diseases, such as rheumatoid arthritis and osteoarthritis, have a higher incidence of CVD. Although recent advances in the treatment of arthritic diseases, the incidence of CVD remains elevated, and MetS has been identified as a possible link between CVD and arthritic diseases. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.030DOI Listing
March 2019
2 Reads

The many facets of macrophages in rheumatoid arthritis.

Biochem Pharmacol 2019 Mar 22. Epub 2019 Mar 22.

Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece; Airway Disease Infection Section, National Heart and Lung Institute, Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, London W2 1NY, United Kingdom. Electronic address:

Macrophages are central to the pathophysiology of rheumatoid arthritis (RA). They constitute the main source of pro-inflammatory cytokines and chemokines such as TNF and IL-1β, they activate a wide range of immune and non-immune cells, and they secrete diverse tissue degrading enzymes driving chronic pro-inflammatory, tissue destructive and pain responses in RA. However, they can also produce anti-inflammatory cytokines such as IL-10, secrete inhibitors of tissue degrading enzymes and promote immunoregulatory and protective responses, suggesting the existence of macrophages with distinct and diverse functional activities. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.029DOI Listing
March 2019
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Mitotic functions of poly(ADP-ribose) polymerases.

Authors:
Dea Slade

Biochem Pharmacol 2019 Mar 22. Epub 2019 Mar 22.

Department of Biochemistry, Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter (VBC), Dr. Bohr-gasse 9, 1030 Vienna, Austria. Electronic address:

Mitosis ensures accurate segregation of duplicated DNA through tight regulation of chromosome condensation, bipolar spindle assembly, chromosome alignment in the metaphase plate, chromosome segregation and cytokinesis. Poly(ADP-ribose) polymerases (PARPs), in particular PARP1, PARP2, PARP3, PARP5a (TNKS1), as well as poly(ADP-ribose) glycohydrolase (PARG), regulate different mitotic functions, including centrosome function, mitotic spindle assembly, mitotic checkpoints, telomere length and telomere cohesion. PARP depletion or inhibition give rise to various mitotic defects such as centrosome amplification, multipolar spindles, chromosome misalignment, premature loss of cohesion, metaphase arrest, anaphase DNA bridges, lagging chromosomes, and micronuclei. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.028DOI Listing

A Disintegrin and Metalloproteinase (ADAM) and ADAM with thrombospondin motifs (ADAMTS) family in vascular biology and disease.

Biochem Pharmacol 2019 Mar 21;164:188-204. Epub 2019 Mar 21.

Vascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address:

A Disintegrin and Metalloproteinase (ADAM) is a family of proteolytic enzymes that possess sheddase function and regulate shedding of membrane-bound proteins, growth factors, cytokines, ligands and receptors. Typically, ADAMs have a pro-domain, and a metalloproteinase, disintegrin, cysteine-rich and a characteristic transmembrane domain. Most ADAMs are activated by proprotein convertases, but can also be regulated by G-protein coupled receptor agonists, Ca ionophores and protein kinase C activators. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.033DOI Listing
March 2019
14 Reads

Long residence time adenosine A receptor agonists produce sustained wash-resistant antilipolytic effect in rat adipocytes.

Biochem Pharmacol 2019 Mar 21;164:45-52. Epub 2019 Mar 21.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China. Electronic address:

Elevated circulating free fatty acid (FFA) level is closely linked to the pathogenesis of insulin resistance and type 2 diabetes mellitus. Activation of the adenosine A receptor (AR) inhibits lipolysis in adipocytes and hence reduces the concentration of FFA, which represents a potential target for the development of antilipolytic agents. We aimed to assess the binding affinity as well as target binding kinetics of AR agonists and further delineate a possible relationship with their antilipolytic effect in adipocytes. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.032DOI Listing
March 2019
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Therapeutic potential of pharmacological TGF-β signaling pathway inhibitors in the pathogenesis of breast cancer.

Biochem Pharmacol 2019 Mar 21;164:17-22. Epub 2019 Mar 21.

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

The TGF-β signaling pathway plays an important role in cancer cell proliferation, growth, inflammation, angiogenesis, and metastasis. The role of TGF-β signaling in the pathogenesis of breast cancer is complex. TGF-β acts as a tumor suppressor in the early stages of disease, and as a tumor promoter in its later stages. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.031DOI Listing

Treatment of polymyalgia rheumatica.

Biochem Pharmacol 2019 Mar 20. Epub 2019 Mar 20.

Division of Rheumatology and Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain; University of Cantabria, Santander, Spain; Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa. Electronic address:

Polymyalgia rheumatica (PMR) is an inflammatory disease characterized by bilateral pain involving predominantly the shoulders and proximal aspects of the arms and less commonly the neck and the pelvic girdle. This review discusses briefly the main epidemiological data and clinical features of this condition. Especial attention is paid in the management of the disease. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.027DOI Listing
March 2019
3 Reads

The osteogenic effect of liraglutide involves enhanced mitochondrial biogenesis in osteoblasts.

Biochem Pharmacol 2019 Mar 15;164:34-44. Epub 2019 Mar 15.

Division of Endocrinology and Center for Research in Anabolic Skeletal Target in Health and Illness (ASTHI), Central Drug Research Institute (CDRI), Council of Scientific and Industrial Research (CSIR), Lucknow 226031, India; AcSIR, CSIR-Central Drug Research Institute Campus, Lucknow 226031, India. Electronic address:

Liraglutide (Lira), a long-acting glucagon-like peptide 1 receptor (GLP1R) agonist reduces glycosylated hemoglobin in type 2 diabetes mellitus patients. Lira is reported to have bone conserving effect in ovariectomized (OVX) rats. Here, we investigated the osteoanabolic effect of Lira and studied the underlying mechanism. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.024DOI Listing
March 2019
14 Reads

Revisiting the combinatorial potential of cytokine subunits in the IL-12 family.

Biochem Pharmacol 2019 Mar 15. Epub 2019 Mar 15.

Unit for Structural Biology, Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 71, 9052 Ghent, Belgium; Unit for Structural Biology, VIB Center for Inflammation Research, Technologiepark-Zwijnaarde 71, 9052 Ghent, Belgium. Electronic address:

The four core members of the Interleukin-12 (IL-12) family of cytokines, IL-12, IL-23, IL-27 and IL-35 are heterodimers which share α- and β-cytokine subunits. All four cytokines are immune modulators and have been proposed to play divergent roles in inflammatory arthritis. In recent years additional combinations of α- and β-cytokine subunits belonging to the IL-12 family have been proposed to form novel cytokines such as IL-39. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.026DOI Listing

Targeting NFE2L2, a transcription factor upstream of MMP-2: A potential therapeutic strategy for temozolomide resistant glioblastoma.

Biochem Pharmacol 2019 Mar 15;164:1-16. Epub 2019 Mar 15.

School of Medical Science and Technology, Indian Institute of Technology Kharagpur, India. Electronic address:

Glioblastoma (GBM) is the most malignant form of brain tumor posing a major threat to cancer amelioration. Temozolomide (TMZ) resistance is one of the major hurdles towards GBM prognosis. Oxidative stress and ECM remodeling are the two important processes involved in gaining chemo-resistance. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.025DOI Listing
March 2019
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High-selective HDAC6 inhibitor promotes HDAC6 degradation following autophagy modulation and enhanced antitumor immunity in glioblastoma.

Biochem Pharmacol 2019 May 15;163:458-471. Epub 2019 Mar 15.

School of Pharmacy, College of Medicine, National Taiwan University, No. 33, LinSen South Road, Taipei 100, Taiwan, ROC; Center for Innovative Therapeutics Discovery, National Taiwan University, No. 33, LinSen South Road, Taipei 100, Taiwan, ROC. Electronic address:

Glioblastoma is the most fatal type of primary brain cancer, and current treatments for glioblastoma are insufficient. HDAC6 is overexpressed in glioblastoma, and siRNA-mediated knockdown of HDAC6 inhibits glioma cell proliferation. Herein, we report a high-selective HDAC6 inhibitor, J22352, which has PROTAC (proteolysis-targeting chimeras)-like property resulted in both p62 accumulation and proteasomal degradation, leading to proteolysis of aberrantly overexpressed HDAC6 in glioblastoma. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.023DOI Listing
May 2019
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Non-NAD-like PARP-1 inhibitors in prostate cancer treatment.

Biochem Pharmacol 2019 Mar 15. Epub 2019 Mar 15.

University of North Dakota, Grand Forks, ND, United States. Electronic address:

In our previous studies of the molecular mechanisms of poly(ADP-ribose) polymerase 1 (PARP-1)-mediated transcriptional regulation we identified a novel class of PARP-1 inhibitors targeting the histone-dependent route of PARP-1 activation. Because histone-dependent activation is unique to PARP-1, non-NAD-like PARP-1 inhibitors have the potential to bypass the off-target effects of classical NAD-dependent PARP-1 inhibitors, such as olaparib, veliparib, and rucaparib. Furthermore, our recently published studies demonstrate that, compared to NAD-like PARP-1 inhibitors that are used clinically, the non-NAD-like PARP-1 inhibitor 5F02 exhibited superior antitumor activity in cell and animal models of human prostate cancer (PC). Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.021DOI Listing
March 2019
3 Reads

Modulation of innate immunity by cyclosporine A.

Biochem Pharmacol 2019 May 15;163:472-480. Epub 2019 Mar 15.

Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02R590 Dublin 2, Ireland. Electronic address:

Cyclosporine A has long been known to suppress T cell responses by inhibiting the production of IL-2, which drives T cell proliferation, enabling its use as a therapeutic for transplantation or autoimmunity. However, cyclosporine A also impacts on innate immune cells including dendritic cells, macrophages and neutrophils. In dendritic cells, which are essential for T cell priming, cyclosporine A can modulate both expression of surface molecules that engage with T cells and cytokine secretion, leading to altered induction of T cell responses. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.022DOI Listing

Hedgehog and Wingless signaling are not essential for autophagy-dependent cell death.

Biochem Pharmacol 2019 Apr 26;162:3-13. Epub 2018 Oct 26.

Centre for Cancer Biology, University of South Australia & SA Pathology, GPO Box 2471, Adelaide, SA 5001, Australia. Electronic address:

Autophagy-dependent cell death is a distinct mode of regulated cell death required in a context specific manner. One of the best validated genetic models of autophagy-dependent cell death is the removal of the Drosophila larval midgut during larval-pupal transition. We have previously shown that down-regulation of growth signaling is essential for autophagy induction and larval midgut degradation. Read More

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http://dx.doi.org/10.1016/j.bcp.2018.10.027DOI Listing

Fighting rheumatoid arthritis: Kv1.3 as a therapeutic target.

Biochem Pharmacol 2019 Mar 14. Epub 2019 Mar 14.

Molecular Physiology Laboratory, Departament de Bioquímica i Biomedicina Molecular, Institut de Biomedicina Universitat de Barcelona (IBUB), Barcelona, Spain. Electronic address:

Rheumatoid arthritis (RA) is a serious autoimmune disease that has severe impacts on both the wellbeing of patients and the economy of the health system. Similar to many autoimmune diseases, RA concurs with a long evolution, which eventually results in highly debilitating symptoms. Therapeutic treatments last for long periods during RA. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.016DOI Listing
March 2019
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Late autophagy inhibitor chloroquine improves efficacy of the histone deacetylase inhibitor SAHA and temozolomide in gliomas.

Biochem Pharmacol 2019 May 13;163:440-450. Epub 2019 Mar 13.

Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address:

Glioblastoma multiforme is the most aggressive type of primary brain tumor associated with few therapeutic opportunities and poor prognosis. In this study, we evaluated the efficacy of combining temozolomide (TMZ) with suberoylanilide hydroxamic acid (SAHA) - a specific histone deacetylases inhibitor - in glioma models in vitro and in vivo. In glioma cell lines, combined TMZ/SAHA promoted more cytotoxicity, G2/M arrest and apoptosis than either drugs alone. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.015DOI Listing
May 2019
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Regulation of fibroblast-like synoviocyte transformation by transcription factors in arthritic diseases.

Biochem Pharmacol 2019 Mar 13. Epub 2019 Mar 13.

Department of Orthopaedics, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.

Inflammation in the synovium is known to mediate joint destruction in several forms of arthritis. Fibroblast-like synoviocytes (FLS) are cells that reside in the synovial lining of joints and are known to be key contributors to inflammation associated with arthritis. FLS are a major source of inflammatory cytokines and catabolic enzymes that promote joint degeneration. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.018DOI Listing
March 2019
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Seno-suppressive molecules as new therapeutic perspectives in rheumatic diseases.

Biochem Pharmacol 2019 Mar 13. Epub 2019 Mar 13.

IRMB (Institut of Regenerative Medicine and Biotherapies), Inserm U1183, Univ Montpellier, Montpellier, France. Electronic address:

Over the past years, through in vitro studies and unique animal models, biologists and clinicians have demonstrated that cellular senescence is at the root of numerous age-related chronic diseases including osteoarthritis and osteoporosis. This non-proliferative cellular syndrome can modify other surrounding tissue-resident cells through the establishment of a deleterious catabolic and inflammatory microenvironment. Targeting these deleterious cells through local or systemic seno-therapeutic agent delivery in pre-clinical models improves dramatically clinical signs and extends health span. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.017DOI Listing
March 2019
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Andrographolide derivative ameliorates dextran sulfate sodium-induced experimental colitis in mice.

Biochem Pharmacol 2019 May 13;163:416-424. Epub 2019 Mar 13.

Institute of Chinese Medical Sciences and State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Avenida da Universidade, Taipa, Macao. Electronic address:

The therapeutic efficacy of immunosuppressive agents has been intensively studied for colitis management. We synthesized a series of andrographolide derivatives and reported their structure-activity-relationship and anti-inflammatory activity in our previous studies. Among these derivatives, compound 3b exhibited the most potent immunosuppressive activity. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.019DOI Listing
May 2019
2 Reads
5.009 Impact Factor

Useful message in choosing optimal biological agents for patients with autoimmune arthritis.

Biochem Pharmacol 2019 Mar 13. Epub 2019 Mar 13.

Institute of Cellular and System Medicine, National Health Research Institute, Zhunan, Taiwan, ROC. Electronic address:

The introduction of biological disease-modifying antirheumatic drug (bDMARD) treatments for various types of autoimmune arthritis, such as rheumatoid arthritis, psoriatic arthropathy and ankylosing spondylitis, represents a new era of treatment for patients with a refractory response to conventional synthetic DMARDs (csDMARDs). Many new bDMARDs with different modalities or that target different pro-inflammatory molecules, likely cytokines, are rapidly emerging. Hence, physicians in the field may be confused about choosing appropriate bDMARDs for their patients. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.007DOI Listing
March 2019
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The science of licking your wounds: Function of oxidants in the innate immune system.

Authors:
Brian J Day

Biochem Pharmacol 2019 May 13;163:451-457. Epub 2019 Mar 13.

Department of Medicine, National Jewish Health, Denver, CO, USA. Electronic address:

Animals often lick their wounds to promote healing. Saliva is thought to have healing properties due to it containing many agents that have antimicrobial properties. A number of these components make up the innate immune system's oxidant generating network. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.013DOI Listing

Role of mitochondrial dysfunction on rheumatic diseases.

Biochem Pharmacol 2019 Mar 9. Epub 2019 Mar 9.

Aging and Inflammation Research Lab, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario A Coruña (CHUAC), Sergas, Universidade da Coruña (UDC), Centro de Investigaciones Científicas Avanzadas (CICA). As Xubias, 15006 A Coruña, Spain. Electronic address:

Rheumatic and musculoskeletal diseases are a heterogeneous group of disorders affecting joint tissues and in some cases even organs, some of them being among the most common diseases worldwide. Mitochondria are the organelles considered as powerhouse of cells providing energy to the organism mainly through oxidative phosphorylation. However, mitochondria are also involved in crucial pathways responsible for maintaining cell physiology, such as the activation of metabolic and survival signaling, and innate and adaptive immune response. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.008DOI Listing
March 2019
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Oncogenic EP300 can be targeted with inhibitors of aldo-keto reductases.

Biochem Pharmacol 2019 May 9;163:391-403. Epub 2019 Mar 9.

Division of Cancer, Imperial College Faculty of Medicine, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, United Kingdom. Electronic address:

E-cadherin transcriptional activator EP300 is down-regulated in metaplastic breast carcinoma, a rare form of triple negative and E-cadherin-negative aggressive breast cancer with a poor clinical outcome. In order to shed light on the regulation of E-cadherin by EP300 in breast cancer we analyzed by immunohistochemistry 41 cases of invasive breast cancer with both E-cadherin and E-cadherin expression levels, together with 20 non-malignant breast tissues. EP300 and E-cadherin showed a positive correlation in both non-malignant and cancer cases and both markers together were better predictors of lymph node metastasis than E-cadherin alone. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00062952193009
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http://dx.doi.org/10.1016/j.bcp.2019.03.009DOI Listing
May 2019
7 Reads
5.009 Impact Factor

Erythromycin acts through the ghrelin receptor to attenuate inflammatory responses in chondrocytes and maintain joint integrity.

Biochem Pharmacol 2019 Mar 9. Epub 2019 Mar 9.

Program in Cellular, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USA; Department of Immunology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA; Program in Pharmacology and Experimental Therapeutics and Pharmacology and Drug Development, Sackler School of Graduate Biomedical Sciences, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USA; Department of Orthopaedics, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA. Electronic address:

Osteoarthritis (OA) is a prevalent disease characterized by chronic joint degeneration and low-grade localized inflammation. There is no available treatment to delay OA progression. We report that in human primary articular chondrocytes, erythromycin, a well-known macrolide antibiotic, had the ability to inhibit pro-inflammatory cytokine Interleukin 1β (IL-1β)-induced catabolic gene expression and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.014DOI Listing
March 2019
1 Read