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    1321 results match your criteria Cyclooxygenase Deficiency

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    Regulator of calcineurin 1 modulates vascular contractility and stiffness through the upregulation of COX-2-derived prostanoids.
    Pharmacol Res 2018 Jan 5. Epub 2018 Jan 5.
    CIBER de Enfermedades Cardiovasculares, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Electronic address:
    Cyclooxygenase-2 (COX-2) derived-prostanoids participate in the altered vascular function and mechanical properties in cardiovascular diseases. We investigated whether regulator of calcineurin 1 (Rcan1) participates in vascular contractility and stiffness through the regulation of COX-2. For this, wild type (Rcan1+/+) and Rcan1-deficient (Rcan1-/-) mice untreated or treated with the COX-2 inhibitor rofecoxib were used. Read More

    Effects of shinbuto and ninjinto on prostaglandin E2 production in lipopolysaccharide-treated human gingival fibroblasts.
    PeerJ 2017 1;5:e4120. Epub 2017 Dec 1.
    Department of Pharmacology, Matsumoto Dental University, Shiojiri, Nagano, Japan.
    Previously, we revealed that several kampo medicines used for patients with excess and/or medium patterns (kakkonto (TJ-1), shosaikoto (TJ-9), hangeshashinto (TJ-14), and orento (TJ-120)) reduced prostaglandin (PG)E2 levels using LPS-treated human gingival fibroblasts (HGFs). Recently, we examined other kampo medicines used for patients with the deficiency pattern [bakumondoto (TJ-29), shinbuto (TJ-30), ninjinto (TJ-32), and hochuekkito (TJ-41)] and the herbs comprising shinbuto and ninjinto using the same experimental model. Shinbuto and ninjinto concentration-dependently reduced LPS-induced PGE2 production by HGFs, whereas hochuekkito weakly reduced and bakumondoto did not reduce PGE2 production. Read More

    Bioassay-guided Isolation of Neuroprotective Fatty Acids from Nigella sativa against 1-methyl-4-phenylpyridinium-induced Neurotoxicity.
    Pharmacogn Mag 2017 Oct-Dec;13(52):627-633. Epub 2017 Nov 13.
    Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
    Objective: Parkinson's disease, a slowly progressive neurological disease, is associated with degeneration of the basal ganglia of the brain and a deficiency of the neurotransmitter dopamine. The main aspects of researches are the protection of normal neurons against degeneration. Fatty acids (FAs), the key structural elements of dietary lipids, are carboxylic straight chains and notable parameters in nutritional and industrial usefulness of a plant. Read More

    Reactive astrocyte COX2-PGE2 production inhibits oligodendrocyte maturation in neonatal white matter injury.
    Glia 2017 Dec 30;65(12):2024-2037. Epub 2017 Aug 30.
    Department of Pediatrics and Division of Neonatology.
    Inflammation is a major risk factor for neonatal white matter injury (NWMI), which is associated with later development of cerebral palsy. Although recent studies have demonstrated maturation arrest of oligodendrocyte progenitor cells (OPCs) in NWMI, the identity of inflammatory mediators with direct effects on OPCs has been unclear. Here, we investigated downstream effects of pro-inflammatory IL-1β to induce cyclooxygenase-2 (COX2) and prostaglandin E2 (PGE2) production in white matter. Read More

    Selenium Deficiency Augments the Levels of Inflammatory Factors and Heat Shock Proteins via the Redox Regulatory Pathway in the Skeletal Muscles of Mice.
    Biol Trace Elem Res 2017 Aug 5. Epub 2017 Aug 5.
    Department of Osteology, The Daqing Oilfield General Hospital, Daqing, 163319, Heilongjiang, People's Republic of China.
    Dietary selenium (Se) deficiency is known to cause myodynia syndrome and Se influences immune responses by changing the expression of inflammatory cytokines and heat shock proteins (Hsps), but the details are not completely elucidated. In the present study, 72 1-day-old mice were divided into two groups; the first group was fed a Se-sufficient diet, while the second group was fed a Se-deficient diet. Skeletal muscles and blood samples were taken from all mice after 42 days of treatment. Read More

    Compensatory Vasodilator Mechanisms in the Ophthalmic Artery of Endothelial Nitric Oxide Synthase Gene Knockout Mice.
    Sci Rep 2017 Aug 2;7(1):7111. Epub 2017 Aug 2.
    Department of Ophthalmology, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany.
    Nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) plays an important role in the maintenance of ocular vascular homeostasis. Therefore, perturbations in vascular NO synthesis have been implicated in the pathogenesis of several ocular diseases. We recently reported that eNOS contributes significantly to vasodilation of the mouse ophthalmic artery. Read More

    Is Aortic Aneurysm Preventable?
    J Transl Int Med 2017 Jun 30;5(2):72-78. Epub 2017 Jun 30.
    UND Life Sciences, 2221, NW 5th St, Battle Ground, WA 98604, USA.
    Abdominal aortic aneurysm (AAA) is a chronic inflammatory condition, triggered by the local accumulation of macrophages, oxidative stress and damage to the aortic wall. Pro-inflammatory eicosanoids seem to play a significant role in AAA. The pro-inflammatory events seen in AAA could be due to a deficiency of anti-inflammatory eicosanoids such as lipoxin A4 (LXA4), resolvins, protectins and maresins as a result of reduced tissue concentrations of their precursors: arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Read More

    MDR1A deficiency restrains tumor growth in murine colitis-associated carcinogenesis.
    PLoS One 2017 7;12(7):e0180834. Epub 2017 Jul 7.
    Experimental Gastroenterology, Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany.
    Patients with Ulcerative Colitis (UC) have an increased risk to develop colitis-associated colorectal cancer (CAC). Here, we found that protein expression of ABCB1 (ATP Binding Cassette Subfamily B Member 1) / MDR1 (multidrug resistance 1) was diminished in the intestinal mucosa of patients with active UC with or without CAC, but not in non-UC patients with sporadic colon cancer. We investigated the consequences of ABCB1/MDR1 loss-of-function in a common murine model for CAC (AOM/DSS). Read More

    Autotaxin-lysophosphatidic acid-LPA3 signaling at the embryo-epithelial boundary controls decidualization pathways.
    EMBO J 2017 07 6;36(14):2146-2160. Epub 2017 Jun 6.
    Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan
    During pregnancy, up-regulation of heparin-binding (HB-) EGF and cyclooxygenase-2 (COX-2) in the uterine epithelium contributes to decidualization, a series of uterine morphological changes required for placental formation and fetal development. Here, we report a key role for the lipid mediator lysophosphatidic acid (LPA) in decidualization, acting through its G-protein-coupled receptor LPA3 in the uterine epithelium. Knockout of Lpar3 or inhibition of the LPA-producing enzyme autotaxin (ATX) in pregnant mice leads to HB-EGF and COX-2 down-regulation near embryos and attenuates decidual reactions. Read More

    Mycobacterium tuberculosis Lipoprotein MPT83 Induces Apoptosis of Infected Macrophages by Activating the TLR2/p38/COX-2 Signaling Pathway.
    J Immunol 2017 Jun 15;198(12):4772-4780. Epub 2017 May 15.
    Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China;
    Tuberculosis caused by Mycobacterium tuberculosis continues to pose a serious global health threat. The attenuated Mycobacterium bovis bacillus Calmette-Guérin, as the only licensed vaccine, has limited protective efficacy against TB. The development of more effective antituberculosis vaccines is urgent and demands for further identification and understanding of M. Read More

    Podocyte-specific knockout of cyclooxygenase 2 exacerbates diabetic kidney disease.
    Am J Physiol Renal Physiol 2017 Aug 10;313(2):F430-F439. Epub 2017 May 10.
    Division of Nephrology, Department of Medicine, Duke University and Durham Veterans Affairs Medical Centers, Durham, North Carolina;
    Enhanced expression of cyclooxygenase 2 (COX2) in podocytes contributes to glomerular injury in diabetic kidney disease, but some basal level of podocyte COX2 expression might be required to promote podocyte attachment and/or survival. To investigate the role of podocyte COX2 expression in diabetic kidney disease, we deleted COX2 specifically in podocytes in a mouse model of Type 1 diabetes mellitus (Akita mice). Podocyte-specific knockout (KO) of COX2 did not affect renal morphology or albuminuria in nondiabetic mice. Read More

    A Randomized Placebo Controlled Trial of Aspirin Effects on Immune Activation in Chronically Human Immunodeficiency Virus-Infected Adults on Virologically Suppressive Antiretroviral Therapy.
    Open Forum Infect Dis 2017 19;4(1):ofw278. Epub 2017 Jan 19.
    Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
    Background: Immune activation persists despite suppressive antiretroviral therapy (ART) in human immunodeficiency virus (HIV) infection and predicts non-Acquired Immune Deficiency Syndrome (AIDS) comorbidities including cardiovascular disease. Activated platelets play a key role in atherothrombosis and inflammation, and platelets are hyperactivated in chronic HIV infection. Aspirin is a potent inhibitor of platelet activation through the cyclooxygenase-1 (COX-1) pathway. Read More

    Loss of Parkin reduces inflammatory arthritis by inhibiting p53 degradation.
    Redox Biol 2017 Aug 5;12:666-673. Epub 2017 Apr 5.
    College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro 194-31, Osong-eup, Heungduk-gu, Cheongju, Chungbuk 361-951, Republic of Korea. Electronic address:
    Parkin is associated with various inflammatory diseases, including Parkinson's disease (PD) and rheumatoid arthritis (RA). However, the precise role of Parkin in RA is unclear. The present study addressed this issue by comparing the development of RA between non-transgenic (non-Tg) mice and PARK2 knockout (KO) mice. Read More

    A novel pH-controlled hydrogen sulfide donor protects gastric mucosa from aspirin-induced injury.
    J Cell Mol Med 2017 Oct 7;21(10):2441-2451. Epub 2017 Apr 7.
    Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.
    Hydrogen sulphide (H2 S) serves as a vital gastric mucosal defence under acid condition. Non-steroidal anti-inflammatory drugs (NSAIDs) are among widely prescribed medications with effects of antipyresis, analgesia and anti-inflammation. However, their inappropriate use causes gastric lesions and endogenous H2 S deficiency. Read More

    Cyclooxygenase-2 Induction by Amino Acid Deprivation Requires p38 Mitogen-Activated Protein Kinase in Human Glioma Cells.
    Cancer Invest 2017 Apr 23;35(4):237-247. Epub 2017 Mar 23.
    a Department of Radiation Oncology and the Winship Cancer Institute , Emory University , Atlanta , Georgia , USA.
    Glioblastomas (GBMs) are malignant brain tumors that can outstrip nutrient supplies due to rapid growth. Cyclooxygenase-2 (COX-2) has been linked to GBMs and may contribute to their aggressive phenotypes. Amino acid starvation results in COX-2 mRNA and protein induction in multiple human glioma cell lines in a process requiring p38 mitogen-activated protein kinase (p38-MAPK) and the Sp1 transcription factor. Read More

    Human mitochondrial cytochrome c oxidase assembly factor COX18 acts transiently as a membrane insertase within the subunit 2 maturation module.
    J Biol Chem 2017 05 22;292(19):7774-7783. Epub 2017 Mar 22.
    From the Departments of Neurology and
    Defects in mitochondrial cytochrome c oxidase or respiratory chain complex IV (CIV) assembly are a frequent cause of human mitochondrial disorders. Specifically, mutations in four conserved assembly factors impinging the biogenesis of the mitochondrion-encoded catalytic core subunit 2 (COX2) result in myopathies. These factors afford stability of newly synthesized COX2 (the dystonia-ataxia syndrome protein COX20), a protein with two transmembrane domains, and maturation of its copper center, CuA (cardiomyopathy proteins SCO1, SCO2, and COA6). Read More

    Salt supplementation ameliorates developmental kidney defects in COX-2-/- mice.
    Am J Physiol Renal Physiol 2017 Jun 8;312(6):F1044-F1055. Epub 2017 Mar 8.
    Institute of Clinical Pharmacology, Goethe-University, Frankfurt, Germany; and
    Deficiency of cyclooxygenase-2 (COX-2) activity in the early postnatal period causes impairment of kidney development leading to kidney insufficiency. We hypothesize that impaired NaCl reabsorption during the first days of life is a substantial cause for nephrogenic defects observed in COX-2-/- mice and that salt supplementation corrects these defects. Daily injections of NaCl (0. Read More

    Equol, a Dietary Daidzein Gut Metabolite Attenuates Microglial Activation and Potentiates Neuroprotection In Vitro.
    Nutrients 2017 Feb 27;9(3). Epub 2017 Feb 27.
    College of Pharmacy, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea.
    Estrogen deficiency has been well characterized in inflammatory disorders including neuroinflammation. Daidzein, a dietary alternative phytoestrogen found in soy (Glycine max) as primary isoflavones, possess anti-inflammatory activity, but the effect of its active metabolite Equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman) has not been well established. In this study, we investigated the anti-neuroinflammatory and neuroprotective effect of Equol in vitro. Read More

    RIP3 deficiency exacerbates inflammation in dextran sodium sulfate-induced ulcerative colitis mice model.
    Cell Biochem Funct 2017 Apr 2;35(3):156-163. Epub 2017 Mar 2.
    Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, China.
    Ulcerative colitis (UC) is a chronic intestinal inflammatory disease. The receptor-interacting protein kinase 3 (RIP3) was reported to be involved in many inflammatory disease. However, the mechanism of RIP3 in the pathogenesis of UC is still unclear. Read More

    Altered metabolic homeostasis between vitamin D and long chain polyunsaturated fatty acids in preeclampsia.
    Med Hypotheses 2017 Mar 17;100:31-36. Epub 2017 Jan 17.
    Department of Nutritional Medicine, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth Deemed University, Pune 411043, India. Electronic address:
    Sub-optimal maternal nutrition may result in pregnancy complications like preeclampsia. Preeclampsia is known to be of placental origin and a major cause of maternal morbidity and mortality worldwide. Our earlier studies suggest that altered metabolism of folic acid, vitamin B12 and long chain polyunsaturated fatty acid (LCPUFAs) in the one carbon cycle increases homocysteine levels in preeclampsia. Read More

    Dual anti-ischemic effects of rosmarinic acid n-butyl ester via alleviation of DAPK-p53-mediated neuronal damage and microglial inflammation.
    Acta Pharmacol Sin 2017 Apr 20;38(4):459-468. Epub 2017 Feb 20.
    CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
    The discovery of efficacious anti-ischemic drugs remains a challenge. Recently we have found that rosmarinic acid n-butyl ester (RABE), a derivative of rosmarinic acid, significantly protects SH-SY5Y cells against oxygen glucose deprivation (OGD)-induced cell death. In the present study we simultaneously investigated the effects of RABE on the two key players in the pathophysiology of cerebral ischemia, ischemic neuronal damage and microglial inflammation. Read More

    A key role for tetrahydrobiopterin-dependent endothelial NOS regulation in resistance arteries: studies in endothelial cell tetrahydrobiopterin-deficient mice.
    Br J Pharmacol 2017 04 13;174(8):657-671. Epub 2017 Mar 13.
    British Heart Foundation Centre of Research Excellence, Division of Cardiovascular Medicine, University of Oxford, Oxford, UK.
    Background And Purpose: The cofactor tetrahydrobiopterin (BH4) is a critical regulator of endothelial NOS (eNOS) function, eNOS-derived NO and ROS signalling in vascular physiology. To determine the physiological requirement for de novo endothelial cell BH4 synthesis for the vasomotor function of resistance arteries, we have generated a mouse model with endothelial cell-specific deletion of Gch1, encoding GTP cyclohydrolase 1 (GTPCH), an essential enzyme for BH4 biosynthesis, and evaluated BH4-dependent eNOS regulation, eNOS-derived NO and ROS generation.

    Experimental Approach: The reactivity of mouse second-order mesenteric arteries was assessed by wire myography. Read More

    A CMC1-knockout reveals translation-independent control of human mitochondrial complex IV biogenesis.
    EMBO Rep 2017 03 12;18(3):477-494. Epub 2017 Jan 12.
    Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA
    Defects in mitochondrial respiratory chain complex IV (CIV) frequently cause encephalocardiomyopathies. Human CIV assembly involves 14 subunits of dual genetic origin and multiple nucleus-encoded ancillary factors. Biogenesis of the mitochondrion-encoded copper/heme-containing COX1 subunit initiates the CIV assembly process. Read More

    Angiotensin II-AT1-receptor signaling is necessary for cyclooxygenase-2-dependent postnatal nephron generation.
    Kidney Int 2017 Apr 28;91(4):818-829. Epub 2016 Dec 28.
    Institute of Clinical Pharmacology, Johann Wolfgang Goethe-University, Frankfurt, Germany. Electronic address:
    Deletion of cyclooxygenase-2 (COX-2) causes impairment of postnatal kidney development. Here we tested whether the renin angiotensin system contributes to COX-2-dependent nephrogenesis in mice after birth and whether a rescue of impaired renal development and function in COX-2-/- mice was achievable. Plasma renin concentration in mouse pups showed a birth peak and a second peak around day P8 during the first 10 days post birth. Read More

    Prostaglandin D2 Attenuates Bleomycin-Induced Lung Inflammation and Pulmonary Fibrosis.
    PLoS One 2016 19;11(12):e0167729. Epub 2016 Dec 19.
    Department of Animal Radiology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
    Pulmonary fibrosis is a progressive and fatal lung disease with limited therapeutic options. Although it is well known that lipid mediator prostaglandins are involved in the development of pulmonary fibrosis, the role of prostaglandin D2 (PGD2) remains unknown. Here, we investigated whether genetic disruption of hematopoietic PGD synthase (H-PGDS) affects the bleomycin-induced lung inflammation and pulmonary fibrosis in mouse. Read More

    Lipid Osteoclastokines Regulate Breast Cancer Bone Metastasis.
    Endocrinology 2017 03;158(3):477-489
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, USA.
    Bone metastasis is a deadly consequence of cancers, in which osteoclast forms a vicious cycle with tumor cells. Bone metastasis attenuation by clinical usage of osteoclast inhibitors and in our osteopetrotic mouse genetic models with β-catenin constitutive activation or peroxisome proliferator-activated receptor γ deficiency fully support the important role of osteoclast in driving the bone metastatic niche. However, the mechanisms for this "partnership in crime" are underexplored. Read More

    Opposite Effects of Mechanical Action of Fluid Flow on Proangiogenic Factor Secretion From Human Adipose-Derived Stem Cells With and Without Oxidative Stress.
    J Cell Physiol 2017 Aug 24;232(8):2158-2167. Epub 2017 Mar 24.
    Valencia Institute of Pathology (IVP), Catholic University of Valencia School of Medicine and Odontology, Valencia, Spain.
    Mechanical forces, hypoxia, and oxidative stress contribute to skin renewal, perfusion, and wound healing, but how are they regulating subcutaneous adipose-derived stem cells (ASCs) in the inflammatory microenvironment associated to skin repair and disorders is unknown. In this study, ASCs were isolated from lipoaspirate samples from plastic surgery patients, primary cultured and their differentiation and secretion of a panel of cytokines with pronounced effects on skin repair and angiogenesis were studied under mechanical stimulation by intermittent fluid flow, 1% hypoxia and oxidative stress by glutathione (GSH) depletion with buthionine sulfoximine (BSO) treatment. Mechanical action of fluid flow did not alter mesenchymal phenotype of CD90+ /CD29+ /CD44+ /CD34- /CD106- /CD45- ASCs; however, it remarkably induced ASC secretion of human umbilical vein endothelial cell (HUVEC) migration-stimulating factors. Read More

    Expression of cyclooxygenase-2 has no impact on survival in adenocarcinoma of the esophagogastric junction but is associated with favourable clinicopathologic features.
    Histol Histopathol 2017 Jul 17;32(7):735-741. Epub 2016 Nov 17.
    Department of Pathology, Section of Hematopathology and Endocrine Pathology, University Hospital of Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
    Background: COX-2 expression induces carcinogenesis and is thought to be an adverse prognostic factor in gastric carcinomas while the prognostic value of DNA mismatch repair (MMR) is still controversial. Concerning adenocarcinomas of the esophagogastric junction, no comprehensive data regarding either factors are available as of yet.

    Objective: We assessed expression of COX-2, MLH1 and MSH2 in adenocarcinoma of the esophagogastric junction in relation to patients' survival and various clinicopathologic features. Read More

    Old drugs with new skills: fenoprofen as an allosteric enhancer at melanocortin receptor 3.
    Cell Mol Life Sci 2017 Apr 16;74(7):1335-1345. Epub 2016 Nov 16.
    The William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
    The efficiency of drug research and development has paradoxically declined over the last decades despite major scientific and technological advances, promoting new cost-effective strategies such as drug repositioning by systematic screening for new actions of known drugs. Here, we performed a screening for positive allosteric modulators (PAMs) at melanocortin (MC) receptors. The non-steroidal anti-inflammatory drug fenoprofen, but not the similar compound ibuprofen, presented PAM activity at MC3, MC4, and MC5 receptors. Read More

    Different Susceptibilities between Apoe- and Ldlr-Deficient Mice to Inflammation-Associated Colorectal Carcinogenesis.
    Int J Mol Sci 2016 Oct 28;17(11). Epub 2016 Oct 28.
    Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City, Gifu 501-1194, Japan.
    Hypercholesterolemia resulting in atherosclerosis is associated with an increased risk of ischemic heart disease and colorectal cancer (CRC). However, the roles of apoliprotein (Apo) E (Apoe) and low-density lipoprotein (Ldl) receptor (Ldlr) in colorectal carcinogenesis have not yet been investigated. In this study, we examined the susceptibility of Apoe-deficient and Ldlr-deficient mice, which are genetic animal models of atherosclerosis to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colorectal carcinogenesis. Read More

    Rev Alerg Mex 2016 Oct-Dec;63(4):373-384
    Universidad de Antioquia. Medellín, Antioquia, Colombia.
    Angioedema is defined as edema of the skin or mucosa, including the respiratory and the gastrointestinal mucosa, which is self-limiting, and in most cases is completely resolved in less than 72 hours. It occurs due to increased permeability of the mucosal and submucosal capillaries and postcapillary venules, with resulting plasma extravasation. There are different types of angioedema: histaminergic (which may be mediated by immunoglobulin E), hereditary, from acquired C1 inhibitor deficiency, from angiotensin converting enzyme inhibitor, bradykinin-mediated, and non-histaminergic idiopathic angioedema. Read More

    The effect of ingested sulfite on active avoidance in normal and sulfite oxidase-deficient aged rats.
    Toxicol Mech Methods 2017 Feb 14;27(2):81-87. Epub 2016 Nov 14.
    a Faculty of Medicine, Department of Physiology , Akdeniz University , Antalya , Turkey.
    The aim of this study was to investigate the possible toxic effects of sulfite on neurons by measuring active avoidance learning in normal and sulfite oxidase (SOX)-deficient aged rats. Twenty-four months of age Wistar rats were divided into four groups: control (C), sulfite-treated group (S), SOX-deficient group (D) and SOX-deficient + sulfite-treated group (DS). SOX deficiency was established by feeding rats with a low molybdenum (Mo) diet and adding 200 ppm tungsten (W) to their drinking water. Read More

    Loss of Endothelial Nitric Oxide Synthase Promotes p25 Generation and Tau Phosphorylation in a Murine Model of Alzheimer's Disease.
    Circ Res 2016 Oct 6;119(10):1128-1134. Epub 2016 Sep 6.
    From the Departments of Anesthesiology and Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN.
    Rationale: Alzheimer's disease has an unknown pathogenesis; however, cardiovascular risk factors are associated with a higher incidence of Alzheimer's disease. A defining feature of endothelial dysfunction induced by cardiovascular risk factors is reduced bioavailable endothelial nitric oxide (NO). We previously demonstrated that endothelial NO acts as an important signaling molecule in neuronal tissue. Read More

    Deficiency of mPGES-1 exacerbates renal fibrosis and inflammation in mice with unilateral ureteral obstruction.
    Am J Physiol Renal Physiol 2017 Jan 26;312(1):F121-F133. Epub 2016 Oct 26.
    Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China;
    Microsomal prostaglandin E2 synthase-1 (mPGES-1), an inducible enzyme that converts prostaglandin H2 to prostaglandin E2 (PGE2), plays an important role in a variety of inflammatory diseases. We investigated the contribution of mPGES-1 to renal fibrosis and inflammation in unilateral ureteral obstruction (UUO) for 7 days using wild-type (WT) and mPGES-1 knockout (KO) mice. UUO induced increased mRNA and protein expression of mPGES-1 and cyclooxygenase-2 in WT mice. Read More

    Signaling of Prostaglandin E Receptors, EP3 and EP4 Facilitates Wound Healing and Lymphangiogenesis with Enhanced Recruitment of M2 Macrophages in Mice.
    PLoS One 2016 6;11(10):e0162532. Epub 2016 Oct 6.
    Department of Molecular Pharmacology, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa, Japan.
    Lymphangiogenesis plays an important role in homeostasis, metabolism, and immunity, and also occurs during wound-healing. Here, we examined the roles of prostaglandin E2 (PGE2) receptor (EP) signaling in enhancement of lymphangiogenesis in wound healing processes. The hole-punch was made in the ears of male C57BL/6 mice using a metal ear punch. Read More

    Mesenchymal Transition of High-Grade Breast Carcinomas Depends on Extracellular Matrix Control of Myeloid Suppressor Cell Activity.
    Cell Rep 2016 09;17(1):233-248
    Molecular Immunology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milan, Italy. Electronic address:
    The extracellular matrix (ECM) contributes to the biological and clinical heterogeneity of breast cancer, and different prognostic groups can be identified according to specific ECM signatures. In high-grade, but not low-grade, tumors, an ECM signature characterized by high SPARC expression (ECM3) identifies tumors with increased epithelial-to-mesenchymal transition (EMT), reduced treatment response, and poor prognosis. To better understand how this ECM3 signature is contributing to tumorigenesis, we expressed SPARC in isogenic cell lines and found that SPARC overexpression in tumor cells reduces their growth rate and induces EMT. Read More

    Altering the Anti-inflammatory Lipoxin Microenvironment: a New Insight into Kaposi's Sarcoma-Associated Herpesvirus Pathogenesis.
    J Virol 2016 Dec 28;90(24):11020-11031. Epub 2016 Nov 28.
    H. M. Bligh Cancer Research Laboratories, Department of Microbiology and Immunology, North Chicago, Illinois, USA
    Lipoxins are host anti-inflammatory molecules that play a vital role in restoring tissue homeostasis. The efficacy of lipoxins and their analog epilipoxins in treating inflammation and its associated diseases has been well documented. Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL) are two well-known inflammation related diseases caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Read More

    Anti-atherogenic effect of Humulus japonicus in apolipoprotein E-deficient mice.
    Int J Mol Med 2016 Oct 1;38(4):1101-10. Epub 2016 Sep 1.
    Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
    Humulus japonicus (HJ) is used as a traditional medicine in Korea owing to its multiple properties including anti-mycobacterial, antioxidant and antihypertensive effects. The present study aimed to examine the anti‑inflammatory and anti-atherogenic effects of a methanol extract of HJ. In lipopolysaccharide-stimulated RAW 264. Read More

    ApoE deficiency promotes colon inflammation and enhances inflammatory potential oxidized-LDL and TNF-α in colon epithelial cells.
    Biosci Rep 2016 Aug 18. Epub 2016 Aug 18.
    LSUHSC, 1700 Tulane Ave, Kenner, Louisiana, 70065, United States
    Although deficiency in Apolipoprotein E (ApoE) is linked to many diseases, its effect on colon homeostasis remains unknown.  ApoE appears to control inflammation by regulating NF-kB.  This study was designed to examine whether ApoE deficiency affects factors of colon integrity in vivo and given the likelihood that ApoE deficiency increases oxidized lipids and TNF-α, this study also examined whether such deficiency enhances the inflammatory potential of oxidized-LDL (oxLDL) and TNF-α, in colon epithelial cells in vitro   Here we show that ApoE deficiency is associated with chronic inflammation systemically and in colonic tissues as assessed by TNF-α levels. Read More

    Celecoxib treatment of fibrous dysplasia (FD) in a human FD cell line and FD-like lesions in mice with protein kinase A (PKA) defects.
    Mol Cell Endocrinol 2017 Jan 4;439:165-174. Epub 2016 Aug 4.
    Section on Endocrinology and Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD 20892, USA. Electronic address:
    Osteochondromyxomas (OMX) in the context of Carney complex (CNC) and fibrous dysplasia (FD)-like lesions (FDLL) in mice, as well as isolated myxomas in humans may be caused by inactivation of PRKAR1A, the gene coding for the type 1a regulatory subunit (R1α) of cAMP-dependent protein kinase (PKA). OMXs and FDLL in mice lacking Prkar1a grow from abnormal proliferation of adult bone stromal cells (aBSCs). Prkar1a and Prkaca (coding for Cα) haploinsufficiency leads to COX2 activation and prostaglandin E2 (PGE2) production that, in turn, activates proliferation of aBSCs. Read More

    The Study of Cyclooxygenase 2 in Human Decidua of Preeclampsia.
    Biol Reprod 2016 09 27;95(3):56. Epub 2016 Jul 27.
    Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China Key Laboratory of Animal Resistance Research, College of Life Science, Shandong Normal University, Ji'nan, Shandong, China
    Preeclampsia (PE), a pregnancy-specific disorder characterized by hypertension and proteinuria beginning after 20 wk of pregnancy, is a major cause of maternal and fetal morbidity and mortality. Delivery of the placenta reverses the immediate clinical manifestations and remains the only reliable treatment for PE. Up to now, the causes of PE are not entirely clear. Read More

    Prostaglandin I2 Suppresses Proinflammatory Chemokine Expression, CD4 T Cell Activation, and STAT6-Independent Allergic Lung Inflammation.
    J Immunol 2016 Sep 25;197(5):1577-86. Epub 2016 Jul 25.
    Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232; and Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232.
    Allergic airway diseases are immune disorders associated with heightened type 2 immune responses and IL-5 and IL-13 production at the site of inflammation. We have previously reported that cyclooxygenase (COX) inhibition by indomethacin augmented allergic airway inflammation in a STAT6-independent manner. However, the key COX product(s) responsible for restraining indomethacin-mediated STAT6-independent allergic inflammation is unknown. Read More

    Cardiovascular Consequences of Prostanoid I Receptor Deletion in Microsomal Prostaglandin E Synthase-1-Deficient Hyperlipidemic Mice.
    Circulation 2016 Jul;134(4):328-38
    From Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, Department of Systems Pharmacology and Translational Therapeutics (S.Y.T., J.M., L.T., S.-C.P., L.C., E.P., G.A.F.); Department of Animal Biology, School of Veterinary Medicine (S.Y.T., G.R.G., J.L.); and Department of Genetics, University of Pennsylvania, Philadelphia (J.M.).
    Background: Inhibitors of cyclooxygenase-2 alleviate pain and reduce fever and inflammation by suppressing the biosynthesis of prostacyclin (PGI2) and prostaglandin E2. However, suppression of these prostaglandins, particularly PGI2, by cyclooxygenase-2 inhibition or deletion of its I prostanoid receptor also predisposes to accelerated atherogenesis and thrombosis in mice. By contrast, deletion of microsomal prostaglandin E synthase 1 (mPGES-1) confers analgesia, attenuates atherogenesis, and fails to accelerate thrombogenesis, while suppressing prostaglandin E2, but increasing biosynthesis of PGI2. Read More

    Deficiency in either COX-1 or COX-2 genes does not affect amyloid beta protein burden in amyloid precursor protein transgenic mice.
    Biochem Biophys Res Commun 2016 09 15;478(1):286-292. Epub 2016 Jul 15.
    Department of Neurosciences, University of California, San Diego, CA 92037, USA; Departments of Medicine and Physiology, National University of Singapore, Yong Loo Lin School of Medicine, Singapore, 117597, Singapore. Electronic address:
    Epidemiologic studies indicate that chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a lower risk for developing Alzheimer's disease (AD). Because the primary mode of action of NSAIDs is to inhibit cyclooxygenase (COX) activity, it has been proposed that perturbed activity of COX-1 or COX-2 contributes to AD pathogenesis. To test the role of COX-1 or COX-2 in amyloid deposition and amyloid-associated inflammatory changes, we examined amyloid precursor protein (APP) transgenic mice in the context of either COX-1 or COX-2 deficiency. Read More

    Simultaneous quantification of PGI2 and TXA2 metabolites in plasma and urine in NO-deficient mice by a novel UHPLC/MS/MS method.
    J Pharm Biomed Anal 2016 Sep 28;129:148-154. Epub 2016 Jun 28.
    Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, 30-348 Krakow, Poland; Chair of Pharmacology, Jagiellonian University, Medical College, Grzegorzecka 16, 31-531 Krakow, Poland. Electronic address:
    The balance between vascular prostacyclin (PGI2) generated mainly via cyclooxygenase-2 (COX-2) and its physiological antagonist platelet-derived thromboxane A2 (TXA2) formed by cyclooxygenase-1 (COX-1) determines cardiovascular homeostasis. In the present work, a novel bioanalytical method for simultaneous quantification of stable plasma and urinary metabolites of PGI2 (6-keto-PGF1α, 2,3-dinor-6-keto-PGF1α) and TXA2 (TXB2, 2,3-dinor-TXB2) using ultra high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC/MS/MS) was developed. The method was validated using artificial plasma and urine and linearity range, intra- and inter-day precision and accuracy, recovery of analytes, relative and absolute matrix effect and stability of analytes were determined. Read More

    [Association of fatty acid metabolism with systemic inflammatory response in chronic respiratory diseases].
    Biomed Khim 2016 Mar;62(3):341-7
    Vladivostok Branch of the Far Eastern Scientific Centre of Physiology and Pathology of Respiration - Institute of Medical Climatology and Rehabilitation, Vladivostok, Russia.
    We examined composition of plasma non-esterified fatty acids (NFAs), erythrocyte fatty acids, levels of eicosanoids in patients with asthma and chronic obstructive pulmonary disease (COPD) with different type of the inflammatory response. The results of our study show that asthma and COPD in remission are associated with changes in the composition NFAs of plasma, FA of erythrocytes, level eicosanoid despite the difference in the regulation of immunological mechanisms of systemic inflammation. These changes are characterized by excessive production of arachidonic acid (20:4n-6) and cyclooxygenase and lipoxygenase metabolites (thromboxane B2, leukotriene B4) and deficiency of their functional antagonist, eicosapentaenoic acid (20:5n-3). Read More

    Cyclooxygenase-2 deficiency impairs muscle-derived stem cell-mediated bone regeneration via cellular autonomous and non-autonomous mechanisms.
    Hum Mol Genet 2016 08 27;25(15):3216-3231. Epub 2016 Jun 27.
    Stem Cell Research Center, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA
    This study investigated the role of cyclooxygenase-2 (COX-2) expression by donor and host cells in muscle-derived stem cell (MDSC)-mediated bone regeneration utilizing a critical size calvarial defect model. We found that BMP4/green fluorescent protein (GFP)-transduced MDSCs formed significantly less bone in COX-2 knock-out (Cox-2KO) than in COX-2 wild-type (WT) mice. BMP4/GFP-transduced Cox-2KO MDSCs also formed significantly less bone than transduced WT MDSCs when transplanted into calvarial defects created in CD-1 nude mice. Read More

    Dietary Linoleic Acid Lowering Reduces Lipopolysaccharide-Induced Increase in Brain Arachidonic Acid Metabolism.
    Mol Neurobiol 2017 Aug 23;54(6):4303-4315. Epub 2016 Jun 23.
    Brain Physiology and Metabolism Section, Laboratory of Neuroscience, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
    Linoleic acid (LA, 18:2n-6) is a precursor to arachidonic acid (AA, 20:4n-6), which can be converted by brain lipoxygenase and cyclooxygenase (COX) enzymes into various lipid mediators involved in the regulation of brain immunity. Brain AA metabolism is activated in rodents by the bacterial endotoxin, lipopolysaccharide (LPS). This study tested the hypothesis that dietary LA lowering, which limits plasma supply of AA to the brain, reduces LPS-induced upregulation in brain AA metabolism. Read More

    A New Model to Study the Role of Arachidonic Acid in Colon Cancer Pathophysiology.
    Cancer Prev Res (Phila) 2016 Sep 23;9(9):750-7. Epub 2016 Jun 23.
    Program in Integrative Nutrition and Complex Diseases, Department of Nutrition and Food Science, Texas A&M University, College Station, Texas. Center for Translational Environmental Health Research, College Station, Texas.
    A significant increase in cyclooxygenase 2 (COX2) gene expression has been shown to promote cylcooxygenase-dependent colon cancer development. Controversy associated with the role of COX2 inhibitors indicates that additional work is needed to elucidate the effects of arachidonic acid (AA)-derived (cyclooxygenase and lipoxygenase) eicosanoids in cancer initiation, progression, and metastasis. We have recently developed a novel Fads1 knockout mouse model that allows for the investigation of AA-dependent eicosanoid deficiency without the complication of essential fatty acid deficiency. Read More

    Cytochrome P450 1B1 Contributes to the Development of Angiotensin II-Induced Aortic Aneurysm in Male Apoe(-/-) Mice.
    Am J Pathol 2016 Aug 11;186(8):2204-2219. Epub 2016 Jun 11.
    Department of Pharmacology, College of Medicine, The University of Tennessee Health Science Center, Memphis, Tennessee. Electronic address:
    Cytochrome P450 (CYP) 1B1 is implicated in vascular smooth muscle cell migration, proliferation, and hypertension. We assessed the contribution of CYP1B1 to angiotensin (Ang) II-induced abdominal aortic aneurysm (AAA). Male Apoe(-/-)/Cyp1b1(+/+) and Apoe(-/-)/Cyp1b1(-/-) mice were infused with Ang II or its vehicle for 4 weeks; another group of Apoe(-/-)/Cyp1b1(+/+) mice was coadministered the CYP1B1 inhibitor 2,3',4,5'-tetramethoxystilbene (TMS) every third day for 4 weeks. Read More

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