An inducibly-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes and INFLAMMATION. It is the target of COX2 INHIBITORS.
A constitutively-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes.
Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes.
A subclass of cyclooxygenase inhibitors with specificity for CYCLOOXYGENASE-2.
Enzyme complexes that catalyze the formation of PROSTAGLANDINS from the appropriate unsaturated FATTY ACIDS, molecular OXYGEN, and a reduced acceptor.
The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa.
A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.
A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes.
Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.
Compounds that bind to and inhibit that enzymatic activity of LIPOXYGENASES. Included under this category are inhibitors that are specific for lipoxygenase subtypes and act to reduce the production of LEUKOTRIENES.
A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis.
A group of compounds that contain the structure SO2NH2.
Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
A stable, physiologically active compound formed in vivo from the prostaglandin endoperoxides. It is important in the platelet-release reaction (release of ADP and serotonin).
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
An anti-inflammatory analgesic and antipyretic of the phenylalkynoic acid series. It has been shown to reduce bone resorption in periodontal disease by inhibiting CARBONIC ANHYDRASE.
An enzyme of the oxidoreductase class primarily found in PLANTS. It catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives.
The physiologically active and stable hydrolysis product of EPOPROSTENOL. Found in nearly all mammalian tissue.
A class of compounds named after and generally derived from C20 fatty acids (EICOSANOIC ACIDS) that includes PROSTAGLANDINS; LEUKOTRIENES; THROMBOXANES, and HYDROXYEICOSATETRAENOIC ACIDS. They have hormone-like effects mediated by specialized receptors (RECEPTORS, EICOSANOID).
A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).
A potent lipoxygenase inhibitor that interferes with arachidonic acid metabolism. The compound also inhibits formyltetrahydrofolate synthetase, carboxylesterase, and cyclooxygenase to a lesser extent. It also serves as an antioxidant in fats and oils.
The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)
A cyclooxygenase inhibiting, non-steroidal anti-inflammatory agent (NSAID) that is well established in treating rheumatoid arthritis and osteoarthritis and used for musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily.
An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS).
A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt.
Enzymes of the isomerase class that catalyze the oxidation of one part of a molecule with a corresponding reduction of another part of the same molecule. They include enzymes converting aldoses to ketoses (ALDOSE-KETOSE ISOMERASES), enzymes shifting a carbon-carbon double bond (CARBON-CARBON DOUBLE BOND ISOMERASES), and enzymes transposing S-S bonds (SULFUR-SULFUR BOND ISOMERASES). (From Enzyme Nomenclature, 1992) EC 5.3.
Cell surface receptors which bind prostaglandins with a high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin E receptors prefer prostaglandin E2 to other endogenous prostaglandins. They are subdivided into EP1, EP2, and EP3 types based on their effects and their pharmacology.
An enzyme found predominantly in platelet microsomes. It catalyzes the conversion of PGG(2) and PGH(2) (prostaglandin endoperoxides) to thromboxane A2. EC
An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout.
An enzyme that catalyzes the oxidation of arachidonic acid to yield 5-hydroperoxyarachidonate (5-HPETE) which is rapidly converted by a peroxidase to 5-hydroxy-6,8,11,14-eicosatetraenoate (5-HETE). The 5-hydroperoxides are preferentially formed in leukocytes.
Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase.
A non-steroidal anti-inflammatory agent with antipyretic and antigranulation activities. It also inhibits prostaglandin biosynthesis.
Eicosatetraenoic acids substituted in any position by one or more hydroxy groups. They are important intermediates in a series of biosynthetic processes leading from arachidonic acid to a number of biologically active compounds such as prostaglandins, thromboxanes, and leukotrienes.
A group of physiologically active prostaglandin endoperoxides. They are precursors in the biosynthesis of prostaglandins and thromboxanes. Most frequently encountered member of this group is the prostaglandin G2.
A saclike, glandular diverticulum on each ductus deferens in male vertebrates. It is united with the excretory duct and serves for temporary storage of semen. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
A 20-carbon unsaturated fatty acid containing 4 alkyne bonds. It inhibits the enzymatic conversion of arachidonic acid to prostaglandins E(2) and F(2a).
A naturally occurring prostaglandin that has oxytocic, luteolytic, and abortifacient activities. Due to its vasocontractile properties, the compound has a variety of other biological actions.
A dual inhibitor of both cyclooxygenase and lipoxygenase pathways. It exerts an anti-inflammatory effect by inhibiting the formation of prostaglandins and leukotrienes. The drug also enhances pulmonary hypoxic vasoconstriction and has a protective effect after myocardial ischemia.
(11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities.
The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.
A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.
Cyclic esters of hydroxy carboxylic acids, containing a 1-oxacycloalkan-2-one structure. Large cyclic lactones of over a dozen atoms are MACROLIDES.
The relationship between the dose of an administered drug and the response of the organism to the drug.
An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.
Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.
A cyclic endoperoxide intermediate produced by the action of CYCLOOXYGENASE on ARACHIDONIC ACID. It is further converted by a series of specific enzymes to the series 2 prostaglandins.
Phospholipases that hydrolyze the acyl group attached to the 2-position of PHOSPHOGLYCERIDES.
An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
A sulfinylindene derivative prodrug whose sulfinyl moiety is converted in vivo to an active NSAID analgesic. Specifically, the prodrug is converted by liver enzymes to a sulfide which is excreted in the bile and then reabsorbed from the intestine. This helps to maintain constant blood levels with reduced gastrointestinal side effects.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system.
A 20-carbon-chain fatty acid, unsaturated at positions 8, 11, and 14. It differs from arachidonic acid, 5,8,11,14-eicosatetraenoic acid, only at position 5.
A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is an NSAID and is used principally for its analgesic activity. (From Martindale The Extra Pharmacopoeia, 31st ed)
Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.
The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates. These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids. The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- .
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Cell surface proteins that bind THROMBOXANES with high affinity and trigger intracellular changes influencing the behavior of cells. Some thromboxane receptors act via the inositol phosphate and diacylglycerol second messenger systems.
The principal cyclooxygenase metabolite of arachidonic acid. It is released upon activation of mast cells and is also synthesized by alveolar macrophages. Among its many biological actions, the most important are its bronchoconstrictor, platelet-activating-factor-inhibitory, and cytotoxic effects.
A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.
A subtype of prostaglandin E receptors that specifically couples to GS ALPHA GTP-BINDING PROTEIN SUBUNITS and subsequently activates ADENYLYL CYCLASES. The receptor may also signal through the activation of PHOSPHATIDYLINOSITOL 3-KINASE.
A subtype of prostaglandin E receptors that specifically couples to GTP-BINDING PROTEIN ALPHA SUBUNIT, GQ and the subsequently activates TYPE C PHOSPHOLIPASES. Additional evidence has shown that the receptor can act through a calcium-dependent signaling pathway.
Compounds that inhibit the action of prostaglandins.
The major metabolite in neutrophil polymorphonuclear leukocytes. It stimulates polymorphonuclear cell function (degranulation, formation of oxygen-centered free radicals, arachidonic acid release, and metabolism). (From Dictionary of Prostaglandins and Related Compounds, 1990)
An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.
A group of physiologically active prostaglandin endoperoxides. They are precursors in the biosynthesis of prostaglandins and thromboxanes. The most frequently encountered member of this group is the prostaglandin H2.
The salts or esters of salicylic acids, or salicylate esters of an organic acid. Some of these have analgesic, antipyretic, and anti-inflammatory activities by inhibiting prostaglandin synthesis.
A non-steroidal anti-inflammatory agent (ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL) similar in mode of action to INDOMETHACIN.
Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.
Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.
A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
A subtype of prostaglandin E receptors that specifically couples to GS ALPHA GTP-BINDING PROTEIN SUBUNITS and subsequently activates ADENYLYL CYCLASES.
A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
A CALCIUM-independent subtype of nitric oxide synthase that may play a role in immune function. It is an inducible enzyme whose expression is transcriptionally regulated by a variety of CYTOKINES.
Cell surface receptors that bind prostaglandins with high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin receptor subtypes have been tentatively named according to their relative affinities for the endogenous prostaglandins. They include those which prefer prostaglandin D2 (DP receptors), prostaglandin E2 (EP1, EP2, and EP3 receptors), prostaglandin F2-alpha (FP receptors), and prostacyclin (IP receptors).
A lipoxygenase metabolite of ARACHIDONIC ACID. It is a highly selective ligand used to label mu-opioid receptors in both membranes and tissue sections. The 12-S-HETE analog has been reported to augment tumor cell metastatic potential through activation of protein kinase C. (J Pharmacol Exp Ther 1995; 274(3):1545-51; J Natl Cancer Inst 1994; 86(15):1145-51)
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.
An IBUPROFEN-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis.
A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is a non-steroidal anti-inflammatory agent used for analgesia for postoperative pain and inhibits cyclooxygenase activity.
An inhibitor of nitric oxide synthetase which has been shown to prevent glutamate toxicity. Nitroarginine has been experimentally tested for its ability to prevent ammonia toxicity and ammonia-induced alterations in brain energy and ammonia metabolites. (Neurochem Res 1995:200(4):451-6)
Drugs used to cause dilation of the blood vessels.
A stable prostaglandin endoperoxide analog which serves as a thromboxane mimetic. Its actions include mimicking the hydro-osmotic effect of VASOPRESSIN and activation of TYPE C PHOSPHOLIPASES. (From J Pharmacol Exp Ther 1983;224(1): 108-117; Biochem J 1984;222(1):103-110)
Endogenously-synthesized compounds that influence biological processes not otherwise classified under ENZYMES; HORMONES or HORMONE ANTAGONISTS.
A group of LEUKOTRIENES; (LTC4; LTD4; and LTE4) that is the major mediator of BRONCHOCONSTRICTION; HYPERSENSITIVITY; and other allergic reactions. Earlier studies described a "slow-reacting substance of ANAPHYLAXIS" released from lung by cobra venom or after anaphylactic shock. The relationship between SRS-A leukotrienes was established by UV which showed the presence of the conjugated triene. (From Merck Index, 11th ed)
A subtype of prostaglandin E receptors that specifically couples to GTP-BINDING PROTEIN ALPHA SUBUNIT, GI and subsequently inhibits ADENYLYL CYCLASES.
A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.
Drugs used to cause constriction of the blood vessels.
A subclass of eicosanoid receptors that have specificity for THROMBOXANE A2 and PROSTAGLANDIN H2.
Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
Substances that reduce or suppress INFLAMMATION.
The smallest divisions of the arteries located between the muscular arteries and the capillaries.
An acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years. It has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. It is used in cell biological experiments as an inhibitor of phospholipase A2.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
(9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1-oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9-carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Lining of the STOMACH, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. The surface cells produce MUCUS that protects the stomach from attack by digestive acid and enzymes. When the epithelium invaginates into the LAMINA PROPRIA at various region of the stomach (CARDIA; GASTRIC FUNDUS; and PYLORUS), different tubular gastric glands are formed. These glands consist of cells that secrete mucus, enzymes, HYDROCHLORIC ACID, or hormones.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
A subcategory of phospholipases A2 that occur in the CYTOSOL.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
Ulceration of the GASTRIC MUCOSA due to contact with GASTRIC JUICE. It is often associated with HELICOBACTER PYLORI infection or consumption of nonsteroidal anti-inflammatory drugs (NSAIDS).
The nonstriated involuntary muscle tissue of blood vessels.
Catalyzes reversibly the oxidation of hydroxyl groups of prostaglandins.
Arteries which arise from the abdominal aorta and distribute to most of the intestines.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Trihydroxy derivatives of eicosanoic acids. They are primarily derived from arachidonic acid, however eicosapentaenoic acid derivatives also exist. Many of them are naturally occurring mediators of immune regulation.
FATTY ACIDS in which the carbon chain contains one or more double or triple carbon-carbon bonds.
The rate dynamics in chemical or physical systems.
An anti-inflammatory 9-fluoro-glucocorticoid.
Elements of limited time intervals, contributing to particular results or situations.
Established cell cultures that have the potential to propagate indefinitely.
A non-steroidal anti-inflammatory agent that is less effective than equal doses of ASPIRIN in relieving pain and reducing fever. However, individuals who are hypersensitive to ASPIRIN may tolerate sodium salicylate. In general, this salicylate produces the same adverse reactions as ASPIRIN, but there is less occult gastrointestinal bleeding. (From AMA Drug Evaluations Annual, 1992, p120)
Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated.
An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in PLATELETS.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions.
A competitive inhibitor of nitric oxide synthetase.
A group of compounds that contain a bivalent O-O group, i.e., the oxygen atoms are univalent. They can either be inorganic or organic in nature. Such compounds release atomic (nascent) oxygen readily. Thus they are strong oxidizing agents and fire hazards when in contact with combustible materials, especially under high-temperature conditions. The chief industrial uses of peroxides are as oxidizing agents, bleaching agents, and initiators of polymerization. (From Hawley's Condensed Chemical Dictionary, 11th ed)
A cytosolic phospholipase A2 group that plays an important role in the release of free ARACHIDONIC ACID, which in turn is metabolized to PROSTAGLANDINS by the CYCLOOXYGENASE pathway and to LEUKOTRIENES by the 5-LIPOXYGENASE pathway.
A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.
A potent vasodilator agent that increases peripheral blood flow.
The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)
A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities.
A class of cyclic prostaglandins that contain the 6,9-epoxy bond. Endogenous members of this family are biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES.
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.
Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.
A doubly unsaturated fatty acid, occurring widely in plant glycosides. It is an essential fatty acid in mammalian nutrition and is used in the biosynthesis of prostaglandins and cell membranes. (From Stedman, 26th ed)
A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.
Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
A drug that has analgesic and anti-inflammatory properties. Following reports of adverse reactions including reports of carcinogenicity in animal studies it was withdrawn from the market worldwide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p21)
A series of prostaglandin-like compounds that are produced by the attack of free-radical species on unsaturated fatty acids, especially ARACHIDONIC ACID, of cellular MEMBRANES. Once cleaved from the lipid membrane by the action of phospholipases they can circulate into various bodily fluids and eventually be excreted. Although these compounds resemble enzymatically synthesized prostaglandins their stereoisometric arrangement is usually different than the "naturally occurring" compounds.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
An inhibitor of drug metabolism and CYTOCHROME P-450 ENZYME SYSTEM activity.
Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.
Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
20-carbon saturated monocarboxylic acids.
Synthetic compounds that are analogs of the naturally occurring prostaglandin endoperoxides and that mimic their pharmacologic and physiologic activities. They are usually more stable than the naturally occurring compounds.
Paracrine substances produced by the VASCULAR ENDOTHELIUM with VASCULAR SMOOTH MUSCLE relaxation (VASODILATION) activities. Several factors have been identified, including NITRIC OXIDE and PROSTACYCLIN.
Cell surface receptors for EPOPROSTENOL. They are coupled to HETEROTRIMERIC G-PROTEINS.
Tumors or cancer of the COLON.
A salicylate derivative and anti-inflammatory analgesic with actions and side effects similar to those of ASPIRIN.
A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-.
Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects.
The main trunk of the systemic arteries.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.
Precursors in the biosynthesis of prostaglandins and thromboxanes from arachidonic acid. They are physiologically active compounds, having effect on vascular and airway smooth muscles, platelet aggregation, etc.
A group of 1,2-benzenediols that contain the general formula R-C6H5O2.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A water-soluble extractive mixture of sulfated polysaccharides from RED ALGAE. Chief sources are the Irish moss CHONDRUS CRISPUS (Carrageen), and Gigartina stellata. It is used as a stabilizer, for suspending COCOA in chocolate manufacture, and to clarify BEVERAGES.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The circulation of the BLOOD through the MICROVASCULAR NETWORK.
A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.
The flow of BLOOD through or around an organ or region of the body.
A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans.
The circulation of the BLOOD through the LUNGS.
The force that opposes the flow of BLOOD through a vascular bed. It is equal to the difference in BLOOD PRESSURE across the vascular bed divided by the CARDIAC OUTPUT.
A diverse group of agents, with unique chemical structures and biochemical requirements, which generate NITRIC OXIDE. These compounds have been used in the treatment of cardiovascular diseases and the management of acute myocardial infarction, acute and chronic congestive heart failure, and surgical control of blood pressure. (Adv Pharmacol 1995;34:361-81)
An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy-5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in NEUTROPHILS and LYMPHOCYTES.
Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
The endogenous compounds that mediate inflammation (AUTACOIDS) and related exogenous compounds including the synthetic prostaglandins (PROSTAGLANDINS, SYNTHETIC).
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS.
Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).
An essential amino acid that is physiologically active in the L-form.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Agents that reduce the frequency or rate of spontaneous or induced tumors independently of the mechanism involved.
A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Fatty acid derivatives that have specificity for CANNABINOID RECEPTORS. They are structurally distinct from CANNABINOIDS and were originally discovered as a group of endogenous CANNABINOID RECEPTOR AGONISTS.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
An antiseptic and disinfectant aromatic alcohol.
Compounds with a 5-membered ring of four carbons and an oxygen. They are aromatic heterocycles. The reduced form is tetrahydrofuran.
The action of a drug in promoting or enhancing the effectiveness of another drug.
A compound composed of a two CYCLIC PEPTIDES attached to a phenoxazine that is derived from STREPTOMYCES parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015)

Characterization of the analgesic and anti-inflammatory activities of ketorolac and its enantiomers in the rat. (1/1406)

The marked analgesic efficacy of ketorolac in humans, relative to other nonsteroidal anti-inflammatory drugs (NSAIDs), has lead to speculation as to whether additional non-NSAID mechanism(s) contribute to its analgesic actions. To evaluate this possibility, we characterized (R,S)-ketorolac's pharmacological properties in vivo and in vitro using the nonselective cyclooxygenase (COX) inhibitors [indomethacin (INDO) and diclofenac sodium (DS)] as well as the selective COX-2 inhibitor, celecoxib, as references. The potency of racemic (R,S)-ketorolac was similar in tests of acetic acid-induced writhing, carrageenan-induced paw hyperalgesia, and carrageenan-induced edema formation in rats; ID50 values = 0.24, 0. 29, and 0.08 mg/kg, respectively. (R,S)-ketorolac's actions were stereospecific, with (S)-ketorolac possessing the biological activity of the racemate in the above tests. The analgesic potencies for (R,S)-, (S)-, and (R)-ketorolac, INDO, and DS were highly correlated with their anti-inflammatory potencies, suggesting a common mechanism. (R,S)-ketorolac was significantly more potent than INDO or DS in vivo. Neither difference in relative potency of COX inhibition for (R,S)-ketorolac over INDO and DS nor activity of (S)-ketorolac at a number of other enzymes, channels, or receptors could account for the differences in observed potency. The distribution coefficient for (R,S)-ketorolac was approximately 30-fold less than for DS or INDO, indicating that (R,S)-ketorolac is much less lipophilic than these NSAIDs. Therefore, the physicochemical and pharmacokinetics properties of (R,S)-ketorolac may optimize the concentrations of (S)-ketorolac at its biological target(s), resulting in greater efficacy and potency in vivo.  (+info)

Coordinate regulation of cyclooxygenase-2 and TGF-beta1 in replication error-positive colon cancer and azoxymethane-induced rat colonic tumors. (2/1406)

Evidence is accumulating which indicates that cyclooxygenase-2 (COX-2) is involved in the pathogenesis of colorectal cancer. We evaluated the expression of COX-2 in replication error-positive (RER) colon cancers, colon cancers metastatic to liver and azoxymethane (AOM)-induced rat colonic tumors. Immunohistochemistry showed that COX-2 was low to undetectable in normal human mucosa, but abundant in the RER adenocarcinomas we examined. COX-2 immunoreactivity in metastatic colon cancers was less abundant, but clearly detectable. In the colon of AOM-treated rats, COX-2 protein was not detectable in normal mucosa, but present in most of the epithelial cells comprising the tumors. The TGF-beta1 staining pattern in these human and rat tumors was similar to that observed for COX-2. The role of TGF-beta in RER adenocarcinomas is complex because of the increased mutation rate of TGF-beta type II receptors. Northern analysis showed abundant TGF-beta1 mRNA in AOM-induced tumors, but not in paired mucosa. TGF-beta1 induced the expression of COX-2 mRNA and protein in intestinal epithelial cells (IEC-6). Chronic TGF-beta1 treatment caused a TGF-beta-dependent overexpression of COX-2 in rat intestinal epithelial cells (RIE-1). TGF-beta1 may regulate COX-2 expression during the colonic adenoma to carcinoma sequence.  (+info)

Cyclooxygenase-2 plays a significant role in regulating the tone of the fetal lamb ductus arteriosus. (3/1406)

Nonselective cyclooxygenase (COX) inhibitors are potent tocolytic agents but have adverse effects on the fetal ductus arteriosus. We hypothesized that COX-2 inhibitors may not affect the ductus if the predominant COX isoform is COX-1. To examine this hypothesis, we used ductus arteriosus obtained from late-gestation fetal lambs. In contrast to our hypothesis, fetal lamb ductus arteriosus expressed both COX-1- and COX-2-immunoreactive protein (by Western analysis). Although COX-1 was found in both endothelial and smooth muscle cells, COX-2 was found only in the endothelial cells lining the ductus lumen (by immunohistochemistry). The relative contribution of COX-1 and COX-2 to PGE2 synthesis was consistent with the immunohistochemical results: in the intact ductus, PGE2 formation was catalyzed by both COX-1 and COX-2 in equivalent proportions; in the endothelium-denuded ductus, COX-2 no longer played a significant role in PGE2 synthesis. NS-398, a selective inhibitor of COX-2, was 66% as effective as the selective COX-1 inhibitor valeryl salicylate and the nonselective COX inhibitor indomethacin in causing contraction of the ductus in vitro. At this time, caution should be used when recommending COX-2 inhibitors for use in pregnant women.  (+info)

Induction of an acetaminophen-sensitive cyclooxygenase with reduced sensitivity to nonsteroid antiinflammatory drugs. (4/1406)

The transformed monocyte/macrophage cell line J774.2 undergoes apoptosis when treated for 48 h with competitive inhibitors of cyclooxygenase (COX) isoenzymes 1 and 2. Many of these nonsteroid antiinflammatory drugs (NSAIDs), but in particular diclofenac, induce during this time period a COX activity that coincides with a robust induction of COX-2 protein. Induction of this activity requires high, apoptosis-inducing concentrations of diclofenac (>100 microM). Prolonged treatment of J774.2 cells with lower doses of diclofenac inhibits COX activity, indicating that diclofenac is a time-dependent, pseudoirreversible inhibitor of COX-2. It is difficult to wash out the inhibition. However, the activity evoked by high concentrations of diclofenac has a profoundly distinct COX active site that allows diclofenac, its inducer, to be washed readily from its active site. The diclofenac-induced activity also has the unusual property of being more sensitive to inhibition by acetaminophen (IC50 = 0.1-1.0 mM) than COX-2 induced with bacterial lipopolysaccharide. Moreover, relative to COX-1 or COX-2, diclofenac-induced enzyme activity shows significantly reduced sensitivity to inhibition by diclofenac or other competitively acting nonsteroid antiinflammatory drugs (NSAIDs) and the enzyme activity is insensitive to aspirin. If the robust induction of COX-2 observed is responsible for diclofenac-induced COX enzyme activity, it is clear that COX-2 can, therefore, exist in two catalytically active states. A luciferase reporter-construct that contains part of the COX-2 structure and binds into the membrane showed that chronic diclofenac treatment of fibroblasts results in marked mobilization of the fusion protein. Such a mobilization could result in enzymatically distinct COX-2 populations in response to chronic diclofenac treatment.  (+info)

Spatiotemporal expression of cyclooxygenase 1 and cyclooxygenase 2 during delayed implantation and the periimplantation period in the Western spotted skunk. (5/1406)

Embryonic development in the western spotted skunk is arrested after blastocyst formation for about 200 days. This developmental arrest is believed to be due to insufficiency of uterine conditions to support continuous development. Implantation and decidualization are defective in cyclooxygenase 2 (Cox2)-, but not Cox1-, deficient mice. We therefore used Northern and in situ hybridization to investigate changes in uterine expression of Cox1 and Cox2 genes during various stages of pregnancy in the spotted skunk. Cox1 was constitutively expressed at all stages of pregnancy examined, but it did exhibit localized up-regulation in the trophoblast and necks of uterine glands at early implantation sites. Cox2 expression was highly regulated with little or no expression during delayed implantation. Cox2 expression was first detected in the uterus and trophoblast prior to blastocyst attachment and remained detectable for 5-6 days after blastocyst attachment. Cox2 expression was also localized in the luminal and glandular epithelia of uterine segments located between implantation chambers. Changes in Cox expression were not correlated with the abrupt increase in uterine weight that occurs simultaneously with renewed embryonic development but was correlated with an influx of serum proteins into the uterus observed in a previous study.  (+info)

A mechanistic study of self-inactivation of the peroxidase activity in prostaglandin H synthase-1. (6/1406)

Prostaglandin H synthase (PGHS) is a self-activating and self-inactivating enzyme. Both the peroxidase and cyclooxygenase activities have a limited number of catalytic turnovers. Sequential stopped-flow measurements were used to analyze the kinetics of PGHS-1 peroxidase self-inactivation during reaction with several different hydroperoxides. The inactivation followed single exponential kinetics, with a first-order rate constant of 0.2-0.5 s-1 at 24 degrees C. This rate was independent of the peroxide species and concentration used, strongly suggesting that the self-inactivation process originates after formation of Compound I and probably with Intermediate II, which contains an oxyferryl heme and a tyrosyl radical. Kinetic scan and rapid scan experiments were used to monitor the heme changes during the inactivation process. The results from both experiments converged to a simple, linear, two-step mechanism in which Intermediate II is first converted in a faster step (0.5-2 s-1) to a new compound, Intermediate III, which undergoes a subsequent slower (0.01-0.05 s-1) transition to a terminal species. Rapid-quench and high pressure liquid chromatography analysis indicated that Intermediate III likely retains an intact heme group that is not covalently linked with the PGHS-1 protein.  (+info)

Inhibition of cyclooxygenase-2 expression by 4-trifluoromethyl derivatives of salicylate, triflusal, and its deacetylated metabolite, 2-hydroxy-4-trifluoromethylbenzoic acid. (7/1406)

The therapeutic potential of drugs that block the induction of cyclooxygenase-2 has been emphasized. When two 4-trifluoromethyl salicylate derivatives [2-acetoxy-4-trifluoromethyl-benzoic acid (triflusal) and its deacetylated metabolite 2-hydroxy-4-trifluoromethylbenzoic acid (HTB)] were compared with aspirin and sodium salicylate as cyclooxygenase-2 (COX-2) inhibitors, we observed that in bacterial lipopolysaccharide-activated human blood, triflusal, aspirin, and HTB, but not sodium salicylate, inhibited COX-2-mediated prostaglandin E2 (PGE2) production (IC50 = 0.16, 0.18, 0.39, and >10 mM, respectively). However, only triflusal and aspirin inhibited purified COX-2 enzyme. To test this apparent discrepancy, we realized that HTB and triflusal (but neither aspirin nor salicylate) produced a concentration-dependent inhibition of COX-2 protein expression in peripheral human mononuclear cells. This observation was further confirmed in a rat air pouch model in vivo, in which both aspirin and triflusal inhibited PGE2 production (ID50 = 18.9 and 11.4 mg/kg p.o., respectively) but only triflusal-treated animals showed a decrease in COX-2 expression. This different behavior may be, at least in part, due to the ability of HTB and triflusal to block the activation of the transcription factor nuclear factor-kappaB to a higher extent than aspirin and sodium salicylate. Thus, in addition to inhibiting the COX-2 activity at therapeutic concentrations, triflusal is able to block through its metabolite HTB the expression of new enzyme, and hence the resumption of PGE2 synthesis. Triflusal and HTB may exert beneficial effects in processes in which de novo COX-2 expression is involved and, in a broader sense, in pathological situations in which genes under nuclear factor-kappaB control are up-regulated.  (+info)

Developmental damage, increased lipid peroxidation, diminished cyclooxygenase-2 gene expression, and lowered prostaglandin E2 levels in rat embryos exposed to a diabetic environment. (8/1406)

Previous experimental studies suggest that diabetic embryopathy is associated with an excess of radical oxygen species (ROS), as well as with a disturbance of prostaglandin (PG) metabolism. We aimed to investigate the relationship between these pathways and used hyperglycemia in vitro (embryo culture for 24-48 h) and maternal diabetes in vivo to affect embryonic development. Subsequently, we assessed lipid peroxidation and gene expression of cyclooxygenase (COX)-1 and -2 and measured the concentration of prostaglandin E2 (PGE2) in embryos and membranes. Both hyperglycemia in vitro and maternal diabetes in vivo caused embryonic dysmorphogenesis and increased embryonic levels of 8-epi-PGF2alpha, an indicator of lipid peroxidation. Addition of N-acetylcysteine (NAC) to the culture medium normalized the morphology and 8-epi-PGF2alpha concentration of the embryos exposed to high glucose. Neither hyperglycemia nor diabetes altered COX-1 expression, but embryonic COX-2 expression was diminished on gestational day 10. The PGE2 concentration of day 10 embryos and membranes was decreased after exposure to high glucose in vitro or diabetes in vivo. In vitro addition of NAC to high glucose cultures largely rectified morphology and restored PGE2 concentration, but without normalizing the COX-2 expression in embryos and membranes. Hyperglycemia/diabetes-induced downregulation of embryonic COX-2 gene expression may be a primary event in diabetic embryopathy, leading to lowered PGE2 levels and dysmorphogenesis. Antioxidant treatment does not prevent the decrease in COX-2 mRNA levels but restores PGE2 concentrations, suggesting that diabetes-induced oxidative stress aggravates the loss of COX-2 activity. This may explain in part the antiteratogenic effect of antioxidant treatment.  (+info)

Cyclooxygenase (COX) is a bifunctional enzyme exhibiting coupled peroxidase and dioxygenase activities.1,2 Human COX-1 and COX-2 are two structurally homologous hemoproteins responsible for the biosynthesis of prostaglandin H2 from arachidonic acid (AA).1-3 They have been found to play great roles in certain diseases, including cancer,4 and nervous system5 and apoptosis-related diseases.6 COX-1 is constitutively expressed in a variety of cells,7 whereas COX-2 is induced by various inflammatory and proliferative stimuli. COX enzymes are important drug targets for the non-steroidal anti-inflammatory drugs. Over the past decades, COX-2 inhibitors have widely been used as anti-inflammatory medicine, although they usually elicit potential cardiotoxic side effects. Hence, many efforts have been made in recent years to eliminate or reduce such kinds of adverse effects.6,8,9 Crystal structure studies10,11 reveal that COX-2 has a larger substrate binding pocket than COX-1 (Fig. S1†), providing the ...
Numerous studies have shown that nitric oxide (NO) interacts with human cyclooxygenase (COX); however, conflicting results exist with respect to their interactions. Herein, recombinant human COX-1 and COX-2 were prepared and treated with NO donors individually under anaerobic and aerobic conditions. The S-nitrosyla
Celecoxibe hampered EMD-induced mitosis and proliferation, which, in association with EMD-increased COX-2 expression, indicates that COX-2 may be involved in the proliferative response of HPLF cells to EMD.
Modelled structure of COX-1 and COX-2.Comparison of modelled structures with their template structures revealed the active sites of located in the enzymes. (A)
ab120295 NS 398, COX-2 inhibitor (CAS番号: 123653-11-2) 分子量: 314.36 化学式: C13H18N2O5S COX-2 阻害剤 アブカムの高純度な生理活性物質(アゴニスト・アンタゴニスト・アクティベーター・阻害剤)
Интерлеукин 17A је протеин који је код људи кодиран IL17A геном.[1][2][3] Протеин кодиран овим геном је проинфламаторни цитокин произведен активираним Т ћелијама.[4] Овај цитокин регулише активности НФ-капаБ и митоген активираних протеин киназа. Овај цитокин може да стимулише изражавање ИЛ-6 и циклооксигеназе-2 (PTGS2/COX-2), као и да појача продукцију нитрик оксида (NO). Високи нивои овог цитокина су асоцирани са неколико хроничних инфламаторних обољења укључујући реуматоидни артритис, псоријазу и мултиплу склерозу.[2] ...
TY - JOUR. T1 - Thromboxane A2 generation, in the absence of platelet COX-1 activity, in patients with and without atherothrombotic myocardial infarction. AU - DeFilippis, Andrew P.. AU - Oloyede, Oluwasegun S.. AU - Andrikopoulou, Efstathia. AU - Saenger, Amy K.. AU - Palachuvattil, Joel M.. AU - Fasoro, Yetunde A.. AU - Guallar, Eliseo. AU - Blumenthal, Roger S.. AU - Kickler, Thomas S.. AU - Jaffe, Allan S.. AU - Gerstenblith, Gary. AU - Schulman, Steven P.. AU - Rade, Jeffrey J.. PY - 2013/10/31. Y1 - 2013/10/31. N2 - Background: Aspirins therapeutic action is via inhibition of platelet cyclooxygenase 1 (COX-1) thromboxane A2 (TxA2) production. The aim of this study was to evaluate TxA2 production, in the absence of platelet COX-1 activity, in coronary atherosclerotic heart disease patients with and without atherothrombotic myocardial infarction (MI). Methods and Results: TxA2 production, in the absence of platelet COX-1 activity, was evaluated in 44 patients taking aspirin on 3 ...
Because metastasis is associated with the majority of cancer-related deaths, its prevention is a clinical aspiration. Prostanoids are a large family of bioactive lipids derived from the activity of cyclooxygenase-1 (COX-1) and COX-2. Aspirin impairs the biosynthesis of all prostanoids through the irreversible inhibition of both COX isoforms. Long-term administration of aspirin leads to reduced distant metastases in murine models and clinical trials, but the COX isoform, downstream prostanoid, and cell compartment responsible for this effect are yet to be determined. Here, we have shown that aspirin dramatically reduced lung metastasis through inhibition of COX-1 while the cancer cells remained intravascular and that inhibition of platelet COX-1 alone was sufficient to impair metastasis. Thromboxane A2 (TXA2) was the prostanoid product of COX-1 responsible for this antimetastatic effect. Inhibition of the COX-1/TXA2 pathway in platelets decreased aggregation of platelets on tumor cells, ...
COX-2 Drugs were recently approved by FDA, USA. After the discovery of COX-2, several new medicines were produced and unlike the earlier NSAIDs, the side effects were significantly reduced. COX-2 medicines were proved to be safer than COX-1 medicines. Even the doctors are prescribing these COX-2 medicines only because of their advantages over COX-1 medicines.. There is a clear difference in DNA and mRNA structures of these two but the end results are same. Even the structure of these two enzymes is almost 60% similar. The effects of these enzymes on arachidonic acid are almost same but their functionality is different. COX-2 is localized to nuclear membrane and endoplasmic reticulum. COX-1 is localized to later one only. For prostaglandin synthesis, these two use different versions of arachidonate.. The best thing about COX-2 is it doesn’t affect the prostaglandins that cause these GI problems in any way. It just stops the synthesis and the user won’t face any discomforts like GI ...
COX1 / Cyclooxygenase 1兔单克隆抗体[EPR5866](ab109025)可与小鼠, 大鼠, 人样本反应并经WB, IP, IHC, Flow Cyt, ICC/IF实验严格验证,被2篇文献引用并得到2个独立的用户反馈。
Cyclooxygenase is an enzyme that produces signals that can lead to pain and inflammation. Medications that inhibit cyclooxygenase...
COX-1抑制劑篩選K548 | COX活性測定試劑盒 | COX-2抑制劑篩選試劑盒 | 環氧合酶2(COX-2)ELISA試劑盒 | PTGS2 / COX-2(人類)ELISA試劑 COX-1抑制劑篩選試劑盒 | 貨號K548 Cyclooxygenase-1 (COX-1) Inhibitor
购买我们的人COX1 / Cyclooxygenase 1肽。ab22901可作为ab2338的封闭肽并经过Blocking实验验证。Abcam提供免费的实验方案,操作技巧及专业的支持。中国80%以上现货。
Rabbit polyclonal COX2 / Cyclooxygenase 2 antibody. Validated in WB, ICC/IF and tested in Mouse, Rat, Human. Cited in 63 publication(s). Independently reviewed in 5 review(s). Immunogen corresponding…
CYCLOOXYGENASE-2: Cyclooxygenase (COX), first purified in 1976 and cloned in 1988, is the key enzyme in the synthesis of prostaglandins (PGs) from arachidonic acid. In 1991, several laboratories identified a product from a second gene with COX activity and called it COX-2. However, COX-2 was inducible, and the inducing stimuli included pro-inflammatory cytokines and growth factors, implying a role for COX-2 in both inflammation and control of cell growth. The two isoforms of COX are almost identical in structure but have important differences in substrate and inhibitor selectivity and in their intracellular locations. Protective PGs, which preserve the integrity of the stomach lining and maintain normal renal function in a compromised kidney, are synthesized by COX-1. In addition to the induction of COX-2 in inflammatory lesions, it is present constitutively in the brain and spinal cord, where it may be involved in nerve transmission, particularly that for pain and fever. PGs made by COX-2 are ...
高い抗原親和性、特異性と安定した品質を兼ね備えたアブカムのウサギ・モノクローナル抗体 RabMAb® ab62331 交差種: Ms,Hu 適用: WB,Flow Cyt,ICC/IF
Mono- and Stereopictres of 5.0 Angstrom coordination sphere of Cobalt atom in PDB 1diy: Crystal Structure Of Arachidonic Acid Bound in the Cyclooxygenase Active Site of Pghs-1
The potential role of arachidonic acid metabolism in the enhancement (promotion) of malignant transformation of C3H/M2 mouse fibroblasts by the tumor promoter 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was investigated using inhibitors of cyclooxygenase and lipoxygenase activities. The promoting effects of TCDD (1.5 pM) and of the reference tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA; 0.4 mM) on carcinogen (N-methyl-N′-nitro-N-nitrosoguanidine or 3-methylcholanthrene)-pre-treated fibroblasts was abolished by cotreatment with indomethacin, hydrocortisone, caffeic acid or nordihydroguaiaretic acid. A differential inhibition was found with N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide, a selective inhibitor of the cyclooxygenase isoenzyme COX-2: the promoting effect of TPA, but not that of TCDD, was abolished. Therefore, the role of the cyclooxygenase isoenzymes COX-1 and COX-2 during chronic exposure to TCDD was studied in more detail. Long-term treatment with TCDD (4-7 weeks) ...
We investigated the effects of Th2 cell-associated cytokines, IL-4, IL-10, and IL-13, on prostaglandin (PG) production by human peripheral blood monocytes (HPBM) in terms of four parameters: PGE2 synthesis; cyclooxygenase activity; protein; and mRNA of two cyclooxygenase isozymes (cyclooxygenase-1 and cyclooxygenase-2). LPS-stimulated PGE2 synthesis and cyclooxygenase activity were suppressed by IL-4, IL-10, or IL-13. Furthermore, the LPS-dependent increase of cyclooxygenase activity in HPBM was attributable to cyclooxygenase-2 because it was inhibited by NS-398 (a cyclooxygenase-2-specific inhibitor). Western and Northern blot analyses revealed that the LPS-induced increases in cyclooxygenase-2 protein and mRNA were attenuated by the addition of IL-4, IL-10, or IL-13. In contrast, cyclooxygenase-1 protein and mRNA were hardly detected in monocytes that were incubated with or without LPS in the presence or absence of IL-4, IL-10, and IL-13. These results suggest that the reduction of LPS-induced ...
The widespread consumption of diets rich in anthocyanin and catechin content prompted the evaluation of their in vitro inhibitory effects on cyclooxygenase (COX) enzymes and on the proliferation .... ...
Prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase, is the key enzyme in prostaglandin biosynthesis, and acts both as a dioxygenase and as a peroxidase. There are two isozymes of PTGS: a constitutive PTGS1 and an inducible PTGS2, which differ in their regulation of expression and tissue distribution. This gene encodes the inducible isozyme. It is regulated by specific stimulatory events, suggesting that it is responsible for the prostanoid biosynthesis involved in inflammation and mitogenesis. [provided by RefSeq, Feb 2009 ...
Malignant mesothelioma (MM) is an uncommon neoplasm that arises from the cells lining the body cavities, in particular the pleural and peritoneal cavities. The treatment of MM is a major challenge with frustrating results for clinicians and patients alike. Despite the adoption of newly developed radiotherapic and chemotherapic regimens, the prognosis remains dismal and only modest improvements have been obtained thus far. In this scenario, a better comprehension of the molecular patterns is of paramount importance. Cyclooxygenases catalyze the rate limiting step in the production of prostanoids. Accumulating data demonstrate that overexpression of these enzymes, and in particular of cyclooxygenases- 2, promotes multiple events involved in tumorigenesis; in addition, numerous studies show that inhibition of cyclooxygenases- 2 can delay or prevent certain forms of cancer. Aim of this review is to discuss the current state of the art in mesothelioma, with a particular emphasis on the recent ...
Non steroidal drugs are mainly known for their activities and use as anti-inflammatory, antipyretic compounds. But, in recent observations, they are exposed to use as an effective alternative compounds to prevent or stimulate different metabolic activities and help in preventing various neoplastic progression. They have specific role in controlling estrogen metabolism during breast cancer progression. Sometimes, they are used as an apoptotic induction in various cancers. Their role in hypoxia induced proliferation is also showing promising results. Different NSAIDs will help to induce the activities of various tumor suppressor genes. As chronic inflammation increases the risk for various cancers, therefore, it is important to eliminate inflammation through anti-Inflammatory compounds where NSAIDs are playing a vital role. Most of them are acting to prevent inflammation either via selective or non-selective COX based mechanism. The non-selective COX inhibitor sulindac and the COX-2 selective ...
Prostaglandin G/H synthases (PGHS), commonly referred to as cyclooxygenases (COX-1 and COX-2), catalyze a key step in the synthesis of biologically active prostaglandins (PGs), the conversion of arachidonic acid (AA) into prostaglandin H2 (PGH2). PGs have important functions in a variety of physiologic and pathologic settings, including inflammation, cardiovascular homeostasis, reproduction, and carcinogenesis. However an evaluation of prostaglandin function in early mammalian development has been difficult due to the maternal contribution of prostaglandins from the uterus. The emergence of zebrafish as a model system has begun to provide some insights into the roles of this signaling cascade during vertebrate development. In zebrafish, COX-1 derived prostaglandins are required for two distinct stages of development, namely during gastrulation and segmentation. During gastrulation, PGE2 signaling promotes cell motility, without altering the cell shape or directional migration of gastrulating ...
Boster Bio Anti-COX2/Cyclooxygenase 2/PTGS2 Antibody Picoband™ catalog # A00084. Tested in WB applications. This antibody reacts with Human, Mouse, Rat. Supplied as 100μg/vial in Lyophilized form antibody.
Indomethacin | COX inhibitor | CAS [53-86-1] | Axon 3318 | Axon Ligand™ with >99% purity available from supplier Axon Medchem, prime source of life science reagents for your research
So the problem has to do with the fact that sometimes our understanding of how the body does what it does is incomplete, and when we isolate a chemical or split a natural chemical down to only part of its molecule, it ends up turning off one bad function of the body but unwittingly turning off some beneficial functions, too. For instance, aspirin inhibits cyclooxygenase, the bodys natural chemical that normally mediates the synthesis of natural chemicals that enable platelets to activate and stick together and form a clot when blood vessel damage occurs so you dont bleed out... some people are inappropriately prone to clotting and need to tone that natural process down a bit, so they take aspirin. Well, unfortunately cyclooxygenase also mediates processes that cause your stomach to protect its lining against its own acid... so inhibiting cyclooxygenase will stop platelets of clot-prone people from clotting inappropriately, but at the same time it has the potential to also cause you to get a ...
two can be acting not solely via cAMP but additionally through PLC, which is usually a downstream effector of EP3 receptors (Asboth et al. 1996); PLC inhibition substantially decreased the response to PGE2 . PGE2 stimulates HA production in lots of other tissues too, such as atheroma (Marzoll et al. 2009). Moreover, synovium express the important synthetic enzymes COX1 and COX2 (Satoh et al. 2008). Nevertheless, PGE2 did not seem to mediate MSHA, since neither the common COX inhibitor indomethacin nor a combination ofC2009 The Authors. Journal compilationC2009 The Physiological SocietyJ Physiol 587.Pathways regulating movement-stimulated Altered functional expression of TRPV1168. To evaluate this possibility, we examined hyaluronan secretionspecific COX1 and COX2 inhibitors inhibited MSHA (Table four, study six). PGE2 In the mutants and also the genetically rescued worms in the WSA levels are raised in arthritis, where their pronounced HA-stimulating effect is probably to be vital in helping ...
are much more active against COX-2 than COX-1. COX-2 inhibitors are effective against inflammation and seem to avoid damage to the GI tract. But, unfortunately, they increase the risk of blood clots - which can cause heart attacks and strokes - because they do not block the synthesis of thromboxane A2 by platelets (which contain only COX-1). So people depending on NSAIDs for their heart protective effects must monitor any use of COX-2 inhibitors carefully ...
are much more active against COX-2 than COX-1. COX-2 inhibitors are effective against inflammation and seem to avoid damage to the GI tract. But, unfortunately, they increase the risk of blood clots - which can cause heart attacks and strokes - because they do not block the synthesis of thromboxane A2 by platelets (which contain only COX-1). So people depending on NSAIDs for their heart protective effects must monitor any use of COX-2 inhibitors carefully ...
Interleukin-1 (IL-1) induces hypophagia, which can be reduced by cyclooxygenase (COX) inhibitors. Earlier studies with COX knockout (COXko) mice suggested that COX2 was more important for hypophagia than COX1. However, behavioral responses occur long before COX2 is induced. Hypophagia was assessed in mice by measuring the intake of sweetened milk in a brief period. The intake was reduced within 30 min after intraperitoneal injection of IL-1β and was depressed for about 2 h. When milk intake was measured 30 to 40 min after IL-1β, COX1ko mice showed an attenuated response, whereas COX2ko mice responded more like wild-type animals. By contrast, 90 to 120 min after IL-1β COX1ko mice responded normally, whereas COX2ko mice showed only small responses. The COX2-selective inhibitor, celecoxib, failed to alter the response to IL-1β 30 min after administration, but low doses antagonized the effects of IL-1β at 90 to 120 min. The COX1-selective inhibitor, SC560, attenuated both the early and late ...
COX1_DICDI (O21042 ), COX2_ACHDO (P29870 ), COX2_ACOIG (Q38S50 ), COX2_ACOWI (P50672 ), COX2_ADABI (P29871 ), COX2_AEDAE (P50692 ), COX2_AILFU (Q3L6W7 ), COX2_AILME (Q2Y0B9 ), COX2_ALBCA (P48889 ), COX2_ALBTU (Q09334 ), COX2_ALLMI (O47870 ), COX2_ALOPA (P98024 ), COX2_ANAPL (P98019 ), COX2_ANIIM (Q38S38 ), COX2_ANOGA (P34840 ), COX2_ANOQU (P33505 ), COX2_ANTAM (Q37369 ), COX2_AOTNI (Q7IC90 ), COX2_APIFL (P50267 ), COX2_APIKO (P50268 ), COX2_APILI (P20375 ), COX2_APOMY (Q38S35 ), COX2_APOSM (Q38S29 ), COX2_APOSY (P50673 ), COX2_APTAU (O03889 ), COX2_ARATH (P93285 ), COX2_ARTSF (Q37706 ), COX2_ARVSO (Q38S26 ), COX2_ASCSU (P24882 ), COX2_ASHGO (Q7YFV7 ), COX2_ATEMI (Q7J6G4 ), COX2_BACP3 (Q03438 ), COX2_BACPE (Q04441 ), COX2_BACSU (P24011 ), COX2_BALBO (Q599A0 ), COX2_BALMU (P41294 ), COX2_BALPH (P24986 ), COX2_BATGR (Q38S23 ), COX2_BERBO (Q38S20 ), COX2_BETVU (P98012 ), COX2_BISBI (Q37416 ), COX2_BISBO (P68296 ), COX2_BOSGA (P68295 ), COX2_BOSIN (P68553 ), COX2_BOSJA (P68294 ), COX2_BOSMU (P68554 ...
Drug Discovery, Drugs, Inflammation, Pain, Therapeutic, Community, Homo, Inhibition, Mechanics, Cyclooxygenase, Cyclooxygenase-1, Literature, Pathologies
Coxs Bazar will be a testing ground for the UN Secretary-Generals Prevention Agenda and for the concept of preventing violent extremism.
The Sunderland Forum deals with all local issues in the chat rooms above. However, this is the General Off Topic Forum. So, this area is for all non-local issues. For example, national news or any other interests etc ...
Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been known to cause renal dysfunction in healthy patients and more pronounced renal effects in patients with cirrhosis and ascites. The use of NSAIDs have been associated with hepatorenal syndrome, a serious and often fatal complication associated with acute decline in renal function in the context of cirrhosis. However, renal safety of selective cyclo-oxygenase-2 (COX-2) and non-selective COX inhibitors has not been well delineated in current research with regards to patients with cirrhosis. This literature review seeks to compare the renal safety of selective and non-selective COX inhibitors in patients with cirrhosis. Methods: A thorough multi-database search was conducted using various combinations of keywords. Each study was evaluated using the Grading of Recommendations, Assessments, Development and Evaluation (GRADE) system. Results: Selective COX-2 inhibitor did not produce statistically significant decrements in renal function,
Title: Implications of the Molecular Basis of Prostacyclin Biosynthesis and Signaling in Pharmaceutical Designs. VOLUME: 12 ISSUE: 8. Author(s):Ke-He Ruan and Jean-Michel Dogne. Affiliation:Division of Hematology,Department of Internal Medicine, University of Texas Health ScienceCenter at Houston, 6431 Fannin St., Houston, Texas 77030, USA.. Keywords:Prostacyclin, Prostaglandin I2, PGI2, Cyclooxygenase-1, COX-1, Cyclooxygenase-2, COX-2, Cytochrome P450, G-protein Coupling Receptor. Abstract: Prostacyclin (PGI2) is one of the major vascular protectors against thrombosis and vasoconstriction, caused by thromboxane A2. Understanding the molecular mechanisms of PGI2 biosynthesis and signaling is crucial to the development of therapeutic approaches to regulate PGI2 functions. This review provides information regarding the most current advances in the findings of the molecular mechanisms for PGI2 biosynthesis in the endoplasmic reticulum (ER) membrane through the coordination between PGI2 synthase and ...
Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane. Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain. Drugs, like Aspirin, that inhibit cyclooxygenase activity have been available to the public for about 100 years. Two cyclooxygenase isoforms have been identified and are referred to as COX-1 and COX-2. Under many circumstances the COX-1 enzyme is produced constitutively (i.e., gastric mucosa) whereas COX-2 is inducible (i.e., sites of inflammation). Non-steroidal anti-inflammatory drugs (NSAID), such as aspirin and ibuprofen, exert their effects through inhibition of COX. The main COX inhibitors are the non-steroidal anti-inflammatory drugs (NSAIDs).. ...
Prostaglandin endoperoxide synthase 2, also referred to as cyclooxygenase 2 (COX-2), is a key enzyme in the conversion of arachidonic acid to prostaglandins and other eicosanoids. Rat intestinal epithelial (RIE) cells were permanently transfected with a COX-2 expression vector oriented in the sense …
Varicocele and diabetes mellitus (DM) have long been recognized to impair male fertility by interfering with both sperm parameters and production, however the molecular mechanism by which these effects occur remains largely unknown. Cyclooxygenases are important in spermatogenesis, but their ultrastructural localization in sperm cells and their role in male infertility have not yet established in humans. In the present study we presented the evidence of constitutive (COX-1) and inducible (COX-2) cyclooxygenase expression in healthy human sperm as well as their expression pattern associated with varicocele and DM. By Western blot analysis the comparison between normal and pathologic samples, showed a constitutive expression of both COX isoforms in the spermatozoa from healthy donors, a significant increase in COX-1 and COX-2 protein levels in both varicocele and diabetic semen samples. Our transmission electron microscopic (TEM) data with immunogold analysis provide the first morphological ...
1PGE: Synthesis and use of iodinated nonsteroidal antiinflammatory drug analogs as crystallographic probes of the prostaglandin H2 synthase cyclooxygenase active site.
PTGS2 (COX-2) is unexpressed under normal conditions in most cells, but elevated levels are found during inflammation. PTGS1 (COX-1) is constitutively expressed in many tissues and is the predominant form in gastric mucosa and in the kidneys. Inhibition of PTGS1 (COX-1) reduces the basal production of cytoprotective PGE2 and PGI2 in the stomach, which may contribute to gastric ulceration. Since PTGS2 (COX-2) is generally expressed only in cells where prostaglandins are upregulated (e.g., during inflammation), drug-candidates that selectively inhibit PTGS2 (COX-2) were suspected to show fewer side-effects[25] but proved to substantially increase risk for cardiovascular events such as heart attack and stroke. Two different mechanisms may explain contradictory effects. Low-dose aspirin protects against heart attacks and strokes by blocking PTGS1 (COX-1) from forming a prostaglandin called thromboxane A2. It sticks platelets together and promotes clotting; inhibiting this helps prevent heart ...
A 740003 tumor development and angiogenesis had been first examined using sarcoma 180 cells that are allogeneic for ddy mice (Fig. 1) . In charge ddy mice treated with automobile solid tumors had been obvious 14 d after cell implantation. Daily oral administration of SC-560 the inhibitor functioning on COX-1 had simply no significant influence on tumor mass selectively. On the other hand the COX-2-selective inhibitors JTE-522 and NS-398 considerably decreased tumor mass as do aspirin a non-selective COX inhibitor (Fig. 1 A and D). The level of tumor-induced angiogenesis was evaluated based on hemoglobin items (Fig. 1 C) which correlated well using the vascular thickness in the tumor under histological evaluation (Fig. 1 B). In keeping with the proclaimed red color from the tumors angiogenesis was significant in vehicle-treated mice (Fig. 1 C and B. Like the results in tumor mass angiogenesis was significantly decreased by treatment with COX-2 inhibitors or aspirin however not with SC-560 (Fig. 1 ...
ptgs2, cox-2, cox2, gripghs, hcox-2, pgg/hs, pghs-2, phs-2; prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase); K11987 prostaglandin-endoperoxide synthase 2 [EC:] ...
We have recently reported that cyclooxygenase (COX)-2-deficiency affects brain upstream and downstream enzymes in the arachidonic acid (AA) metabolic pathway to prostaglandin E2 (PGE2), as well as enzyme activity, protein and mRNA levels of the reciprocal isozyme, COX-1. To gain a better insight into the specific roles of COX isoforms and characterize the interactions between upstream and downstream enzymes in brain AA cascade, we examined the expression and activity of COX-2 and phospholipase A2 enzymes (cPLA2 and sPLA2), as well as the expression of terminal prostaglandin E synthases (cPGES, mPGES-1, and − 2) in wild type and COX-1-/- mice. We found that brain PGE2 concentration was significantly increased, whereas thromboxane B2 (TXB2) concentration was decreased in COX-1-/- mice. There was a compensatory up-regulation of COX-2, accompanied by the activation of the NF-κB pathway, and also an increase in the upstream cPLA2 and sPLA2 enzymes. The mechanism of NF-κB activation in the ...
This review summarizes our current understanding of the role of cyclo-oxygenase inhibitors (COXI) in influencing the structural development as well as the function of the developing kidney. COXI administered either during pregnancy or after birth can influence kidney development including nephronogenesis, and can decrease renal perfusion and ultrafiltration potentially leading to acute kidney injury in the newborn period. To date, which COX isoform (COX-1 or COX-2) plays a more important role in during fetal development and influences kidney function early in life is not known, though evidence points to a predominant role for COX-2. Clinical implications of the use of COXI in pregnancy and in the newborn infant are also evaluated herein, with specific reference to the potential effects of COXI on nephronogenesis as well as newborn kidney function.
TY - JOUR. T1 - Increased expression of cyclooxygenase 2 frequently occurs in human lung cancers, specifically in adenocarcinomas.. AU - Kozaki, Kenichi. PY - 1998. Y1 - 1998. M3 - Article. VL - 58. SP - 3761. EP - 3764. JO - Cancer Research. JF - Cancer Research. IS - 17. ER - ...
Rabbit recombinant monoclonal COX2 / Cyclooxygenase 2 antibody [EPR18376-119] validated for WB, IP, Flow Cyt, ICC/IF and tested in Mouse. Immunogen…
S-2474 is an inhibitor of COX-2 and 5-lipoxygenase (5-LO), with IC50s of 11 nM and 27 μM for COX-2 and COX-1 in human intact cells, and used as a nonsteroidal anti-inflammatory drug. - Mechanism of Action & Protocol.
Cox-2 potency refers to the ability of a product to ibuprofen control group; dosing in the control reduce the amount of Cox-2 enzyme in the blood by a group was a single two tablet dose (400 mg.). given percent. For example, a product which inhibits Blood samples were taken immediately before Cox-2 enzyme by a maximum of 50% within a given the dosing of test products, as well as at sampling period is more potent than one that inhibits it subjects in the control group gave blood Cox-2 selectivity refers to the degree to which a product is able to inhibit Cox-2 without inhibiting Cox-1. immediately before dosing, and 0.5, 1, 2, and Selectivity is calculated by dividing the integrated Cox- 1 potency by the integrated Cox-2 potency (see below). The smaller the number below one, the greater the Cox- Plasma from each of the blood samples were evaluated for potency and selectivity in a Integrated potency is potency over time: for example, if validated ex vivo assay. It should be noted that the only way ...
... and cyclooxygenase 2 (COX-2) metabolize linoleic acid to 13(S)-HODE with COX-2 exhibiting a higher preference for linoleic acid ... COX-2 appears to be the principle COX making 13(S)-HODE in cells expressing both enzymes.[11] Concurrently with their ... 1 (4): 165-75. doi:10.1177/2042018810381066. PMC 3474614. PMID 23148161.. *^ a b Vangaveti, Venkat N; Shashidhar, Venkatesh M; ... 11-octadecadienoic acid from linoleic acid by fatty acid cyclooxygenase". Biochimica et Biophysica Acta (BBA) - Lipids and ...
Cox Enterprises. Retrieved July 1, 2020. "Eatonton Confederate Monument, Eatonton, GA". UNF Digital Commons. "Dutchy - ... The County Commission of DeKalb County voted 6-1 to ask its attorneys to find a legal way to remove or relocate it. ... February 1, 2019. Corson, Pete. "Photos: Confederate memorials in metro Atlanta". Atlanta Journal-Constitution. Retrieved May ... "Gettysburg at Savannah Part 1". Gettysburg Daily. May 2, 2011. Retrieved August 28, 2017. "Gettysburg at Savannah Part 2". ...
Cox, Harold. "House Members N". Wilkes University Election Statistics Project. Wilkes University.. ...
Cox, Harold. "House Members M". Wilkes University Election Statistics Project. Wilkes University. v t e. ...
Cox. pp. 365-370. Retrieved 2013-10-16. Richardson, Charles (1908). The Complete Foxhunter. Methuen. p. 17. Retrieved 2013-10- ... 1. London: J. Murray. p. 292. Retrieved 2013-10-20. Crittall, Elizabeth (1959). "Sport". A History of the County of Wiltshire: ... In 1963, a Joint Committee was elected and the hunts were reunited on 1 May 1964. In November, 1981, when wild storms lashed ... ISBN 978-1-84358-686-9. "Hunting Appointments". The Standard. Gale 19th Century British Newspapers. 1886-11-27. Gibbs, J. ...
Cox, James H; Justice, Daniel Heath (eds.). "Literature and the Red Atlantic". Oxford Handbooks Online. doi:10.1093/oxfordhb/ ... ISBN 1-55521-537-8. Tower, W. S. (1907). A History of the American Whale Fishery. University of Philadelphia. Webb, Robert ... 25 (1). ISSN 0898-7084. Retrieved 2019-01-06. Federal Writers' Project. Whaling Masters. Works Progress Administration. ... ISBN 978-1-4696-5334-1. OCLC 1112670580. Mawar (1999), pp. 339-340. Pacific American Steamship Association; Shipowners ...
Cox, Harold (November 3, 2004). "Pennsylvania House of Representatives - 1973-1974" (PDF). Wilkes University Election ... Cox, Harold. "House Members G". Wilkes University Election Statistics Project. Wilkes University. v t e. ...
"Cox(?), Smith, Kidwell, Evans, Ravenscroft in". Lewiston Morning Tribune. (Idaho). Associated Press. August 7, 1974. p. 1. http ... p. 1. Shelledy, Jay (March 19, 1976). "Church joins race for White House". Lewiston Morning Tribune. (Idaho). p. 1A. "Sen. ...
There are 28,000 living in two UN refugee camps in Cox's Bazaar as well as some 200,000 "unregistered people of concern" living ... 1 090 000. 1 860 000. 47.3. 17.5. 29.8. 6.91. 144.4. 1970-1975. 3 193 000. 1 847 000. 1 346 000. 46.5. 26.9. 19.6. 6.91. 175.6 ... 1 153 000. 2 229 000. 44.7. 15.2. 29.5. 6.65. 138.3. 1980-1985. 3 670 000. 1 151 000. 2 519 000. 42.4. 13.3. 29.1. 5.99. 122.5 ... 1 CBR = crude birth rate (per 1000); CDR = crude death rate (per 1000); NC = natural change (per 1000); TFR = total fertility ...
The district of Rangamati consists of 10 upazilas, 1 municipality (9 wards and 35 mahallas), 50 union parishads, 162 mouzas and ...
Carolyn Cox of The Mary Sue later commented on the issue, noting: "Considering how far in advance of their air date Adventure ... Cox, Carolyn (December 1, 2014). "Misantry! Adventure Time Alarms Fans With Apparent Gamergate Reference". The Mary Sue. ... Adventure Time production staff (December 1, 2014). "'Dentist' Deleted Scene". KingOfOoo. Tumblr. Retrieved December 2, 2014. ...
Cox, Beth (August 1, 2019). "Parsons third runner-up at Miss America Outstanding Teen Competition". The Tomahawk. Bazaldua, ... July 1, 2019. The new Miss Arizona's Outstanding Teen is Katelyn Cai... Watson, Ansley (June 20, 2019). "Miss Arkansas' ... June 1, 2019. "Miss Outstanding Teen crowned". The Tennessean. March 31, 2019. Brand, Aaron (July 2, 2019). "Texarkana's Allie ...
Cox, Katie (July 20, 2017). "Kroger to renovate and reopen 7 former Marsh stores, hire hundreds of former Marsh employees". ...
Cox, David (July 1, 2013). "The Internship: how cinema sold its soul - but didn't get paid". The Guardian (UK). Archived from ... The Guardian's David Cox described the movie as a "two-hour corporate video," while British film critic Mark Kermode called the ... CS1 maint: discouraged parameter (link) "Mark Kermode reviews The Internship" on YouTube, The Guardian (UK), 1 July 2013. "'The ...
Cox, Tony (November 1, 2006). "Providing Bait for Nigerian Scam Artists". NPR. Retrieved December 14, 2020. Gordon, Bennett ( ... ISBN 978-1-138-02276-8. Rosenbaum, Ron (June 2007). "How To Trick an Online Scammer Into Carving a Computer Out of Wood". The ... ISBN 978-1-4799-2246-8. Nakamura, Lisa (December 1, 2014). "'I WILL DO EVERYthing That Am Asked': Scambaiting, Digital Show- ... Pest eens een internetfraudeur Basta on YouTube (in Dutch) Archived 2016-05-08 at the Wayback Machine [1]. YouTube D'Anastasio ...
Cox, Michael (26 March 2010). "How the 2000s changed tactics #2: Classic Number 10s struggle". Archived from ... 1-2-7 formation In the sport's early days, football was very much focused on attack and, as such, many teams (such as Royal ... In a 4-4-2 or 4-4-1-1 formation the centre forward is often paired with a second striker who may play around him or in a ... Sometimes a team may opt on a more defensive formation such as 4-5-1 in which the centre forward is required to play a "lone ...
Cox, Matthew (March 1, 2007). "Better than M4, but you can't have one". Army Times. Retrieved 2007-03-15. Army takes HK416s ... 1 June 1968 Danford Allan Kern The influence of organizational culture on the acquisition of the m16 rifle. A ... 1-2 "Tehelka - The People's Paper". Archived from the original on 2013-05-11. Small arms in Africa: Counting the cost of gun ... ISBN 978-1-84908-907-4. Arms of the Chosin Few. Retrieved on 2011-11-23. Donald L. Hall An effectiveness ...
Cox, Anna (August 2, 2000). "Plans for 108-storey skyscraper in Jo'burg". Independent Online. Archived from the original on ... p. B.1.Fro. Kissel, William "Home and Peace", American Way (July 15 2005) Gadd, Jane (December 5, 2003). "Instant karma in a ... p. W.1. Krause, Kevin (March 17, 2003). "Maharishi Fund Puts 300 Acres in The Colony, Texas, Up for Sale". Knight Ridder ... 23 (37). p. 1. [1] Long Vacant Hotel in Downtown Hartford Sells, January 31, 2011 [2] NY Buyer paid $500K for Hartford's empty ...
Cox. Collier, John Payne; Percy Society (1840). "The Reading Skirmish". Early English poetry, ballads, and popular literature ... 1. London: Everyman's Library. pp. 290-298. Information Services. Childs, W.M. (2003) [1905], "The Story of the Town of Reading ...
Cox, Michael; Nelson, David R.; Lehninger, Albert L (2005). Lehninger Principles of Biochemistry. San Francisco: W.H. Freeman. ... Mtb ICDH-1 is most structurally similar to the R132H mutant human ICDH found in glioblastomas. Similar to human R132H ICDH, Mtb ... 372 (1): 130-49. doi:10.1016/j.jmb.2007.06.040. PMID 17632124. Capper D, Zentgraf H, Balss J, Hartmann C, von Deimling A ( ... 108 (1): 11-27. doi:10.1007/s11060-011-0793-0. PMC 3337398. PMID 22270850. Hartmann C, Hentschel B, Wick W, et al. (December ...
Cox, Paul; Fawcett, Tom (2006). DIY: The Rough Trade Story. Orion. ISBN 0-7528-5358-9. Reynolds, Simon (2006). Rip it Up and ... which is listed as Play 1. Bristol Archive Records are currently providing Recreational back catalogue tracks for download, ...
Cox Enterprises. May 1, 2014. Retrieved August 8, 2020. Kelley, Collin (October 18, 2016). "Report: Kodak building to become ...
Wendell Cox; Hugh Pavletich (2012). 8th Annual Demographia International Housing Affordability Survey: 2012 Ratings for ... Wendell Cox; Hugh Pavletich (2012). 8th Annual Demographia International Housing Affordability Survey: 2012 Ratings for ... Gao, Lu (April 1, 2010). "Achievements and Challenges: 30 Years of Housing Reforms in the People's Republic of China". Asian ... Oliner, Stephen D. (1 July 2016). "Housing Conundrum: A Shortage of Demand or Supply?". Business Economics. 51 (3): 161-165. ...
Cox Enterprises. Associated Press. July 10, 1982. p. 11. Retrieved July 21, 2020 - via Dawidziak, Mark (July 13 ... Cox Enterprises. June 1, 1997. p. 4B. Retrieved July 22, 2020 - via WebMasters, Mike Olszewski (2002-03-04). " ... On January 1, 1977 WBOE increased to an 18-hour-per-day, 7-day-a-week schedule (6:00 a.m. to midnight). Programming for in- ... On January 1, 1949, a modified license authorized WBOE to broadcast solely on 90.3 MHz, increasing its transmitter power to ...
He earned his M.B.A. from Southern Methodist University's Cox School of Business in 1989. Mr. Rimer has been married to Jane ... CS1 maint: discouraged parameter (link) "Faculty Directory: Kirk Rimer". SMU Cox. Retrieved 1 May 2016. CS1 maint: discouraged ... Retrieved 1 May 2016. CS1 maint: discouraged parameter (link) "Crow Holdings Capital Partners, L.l.c." Money. US News. ... Retrieved 1 May 2016. CS1 maint: discouraged parameter (link) "Home Research Local News For Sale Real Estate Agents Mortgage ...
Cox, Gary. "April 1, 2020 (letter to county health departments)" (PDF). Oklahoma State Department of Health. Retrieved April 3 ... There are now enough supplies for 13,000 tests, so the commissioner of health Gary Cox and the governor urged health care ... On April 1, the number of cases grew to 719, an increase of 27%. Greer County was added to the list of counties with COVID-19 ... Querry, K (September 1, 2020). "Stitt urges all Oklahomans to wear a mask to slow spread of COVID-19". Oklahoma City. ...
Cox Enterprises. March 16, 2017. Retrieved August 29, 2020. "From "Archer" to "Tiny Doors," bid on unique items at "Party for ... Cox Enterprises. October 5, 2016. Retrieved August 29, 2020. Croitoru, Evelina (March 31, 2017). "YOO on the Park Opens in ... Layman, Tonya (February 1, 2019). "Midtown's historic buildings add character to district". Atlanta Business Chronicle. ...
296-297 Cox; Gray, Air Power History, p. 238 Stephens, Power Plus Attitude, p. 177 "No. 48468". The London Gazette (Supplement ... Cox, Sebastian; Gray, Peter (2008). Air Power History: Turning Points from Kitty Hawk to Kosovo. London: Frank Cass. ISBN 0- ... On 1 September 1950, McNamara was granted a permanent commission in the RAAF. From 1951 to 1953, he served as an instructor at ... He was commissioned as a pilot officer in the Citizen Air Force on 1 May 1944, and was promoted to flying officer on 1 November ...
Cox Enterprises. p. 1. Retrieved 26 May 2011. Palomo, Tony; Katherine Aguon (31 August 2010). "WWII: From Occupation to ... p. 1. Retrieved 25 May 2011. "Guam Stand Praised; Foe Quotes Governor". The New York Times. 18 January 1942. p. 4. Register of ... p. 1. McMillin, George (April-September 1972). Carano, Paul (ed.). "Surrender of Guam to the Japanese". Guam Recorder. Guam: ...
Cox, Eric. "St. Louis lieutenant accused of making racist Facebook post". Retrieved February 1, 2019. "'Rogue' Cop ... "SLMPD District 1". "SLMPD District 2". "SLMPD District 3". "SLMPD District 4". " ... Retrieved October 1, 2012. Scheiber, Noam; Stockman, Farah; Goodman, J. David (June 6, 2020). "How Police Unions Became Such ... Retrieved February 1, 2019. Kilgore, Ed (November 29, 2018). "4 St. Louis Police Officers Indicted on Federal Civil Rights ...
Yi, John S.; Cox, Maureen A.; Zajac, Allan J. T-cell exhaustion: characteristics, causes and conversion. Immunology. 2010-04, ... T细胞耗竭的直接原因包括持续的抗原刺激、以及CD4细胞的缺失[42]。长时间的抗原暴露和高病毒负载可以加重T细胞耗竭的程度。2-4周的持续抗原暴露就可导致T细胞耗竭[43]。另一个可以导致T细胞耗竭的因素是包括PD-1在内的一系列抑制性受体[44][45 ...
Nelson, D. L.; Cox, M. M. (2000) Lehninger, Principles of Biochemistry. 3rd Ed. Worth Publishing: New York. ISBN 1-57259-153-6. ... 33: 1. doi:10.15227/orgsyn.033.0001.. *^ Moffett, R. B.; Shriner, R. L. (1941). "ω-Methoxyacetophenone". Organic Syntheses. 21 ... 978-0-470-46259-1. .. *^ Mendham, J.; Denney, R. C.; Barnes, J. D.; Thomas, M. J. K. (2000), Vogel's Quantitative Chemical ... 978-0-471-72091-1. *^ Marvel, C. S.; Sperry, W. M. (1928). "Benzophenone". Organic Syntheses. 8: 26. doi:10.15227/orgsyn. ...
David L. Nelson, Michael M. Cox (2005). Principles of Biochemistry (4th izd.). New York: W. H. Freeman. ISBN 0-7167-4339-6. ... doi:10.1016/S1574-1400(08)00012-1. *↑ Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). " ... InChI=1S/C3H8O10P2/c4-3(5)2(13-15(9,10)11)1-12-14(6,7)8/h2H,1H2,(H,4,5)(H2,6,7,8)(H2,9,10,11) Y. Kod: XOHUEYCVLUUEJJ-UWTATZPHSA ... ISBN 950-06-1876-1.. *González-Cinca N, Pérez de la Ossa P, Carreras J, Climent F."Effects of thyroid hormone and hypoxia on 2, ...
Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. ISBN 1-57259-153-6. ... 150-30-1 (DL) , 63-91-2 (L). Fenüülalaniin (lühend Phe või F)[2] on organismi- ja toiduvalkudes sisalduv aromaatne α-aminohape ... Eestis sünnib igal aastal 1-3 fenüülketonuuriaga last. Sündides näib laps olevat täiesti terve. ...
Midshipman Phil Cox Vannais, and[16]. *Midshipman Frederick R. Zito.[16]. Post-graduation service obligations[edit]. ... About 1/3 enter the military as active duty Commissioned Officers. Of those going on active duty, most enter the Navy as Naval ... On average about 1/3 of each graduating class goes to sea working in the Merchant Marines as Strategic Sealift Officers serving ... Be at least 17 years of age and must not have passed his or her 25th birthday before July 1 in the year of entrance. ...
Cox, C. Barry & Moore, Peter D. (1993): Biogeography. An ecological and evolutionary approach (5th ed.). Blackwell Scientific ... according to the ICS, as of 2017.[1]. The Miocene ( /ˈmaɪəˌsiːn/[2][3]) is the first geological epoch of the Neogene Period and ... 55: 1-18. doi:10.1016/j.jsames.2014.06.008.. *^ Nielsen, S.N. (2005). "Cenozoic Strombidae, Aporrhaidae, and Struthiolariidae ( ...
Cox, A.J. (2002). "An experiment to measure Mie and Rayleigh total scattering cross sections". American Journal of Physics. 70 ... 1. +. cos. 2. ⁡. θ. 2. R. 2. (. 2. π. λ. ). 4. (. n. 2. −. 1. n. 2. +. 2. ). 2. (. d. 2. ). 6. {\displaystyle I=I_{0}{\frac {1+ ... 1. n. 2. +. 2. ). 2. {\displaystyle \sigma _{\text{s}}={\frac {2\pi ^{5}}{3}}{\frac {d^{6}}{\lambda ^{4}}}\left({\frac {n^{2}-1 ... 1. +. cos. 2. ⁡. θ. ). {\displaystyle I=I_{0}{\frac {\pi ^{2}V^{2}\sigma _{\epsilon }^{2}}{2\lambda ^{4}R^{2}}}{\left(1+\cos ^{ ...
Simpson NB, Cunliffe WJ (2004). "Disorders of the sebaceous glands". In Burns, Tony, Breathnach, Stephen, Cox, Neil, Griffiths ... Retrieved 1 January 2019.. *^ a b c d e f g h i j Barbieri JS, Spaccarelli N, Margolis DJ, James WD (February 2019). " ... 1: 15033. doi:10.1038/nrdp.2015.33. PMID 27227877.. *^ a b "Frequently Asked Questions: Acne" (PDF). U.S. Department of Health ... 28 (1): 6-37. doi:10.2165/00003495-198428010-00002. PMID 6235105.. *^ a b Rasmusson GH (1986). Chemical Control of Androgen ...
Orange Is the New Black, season 3 (2015): Aduba, Birbiglia, Blake, Brooks, Cox, Cruz, Curtin, DeLaria, Fowler, Glenn, Golden, ... Orange Is the New Black, season 2 (2014): Aduba, Biggs, Brooks, Cox, Cruz, Curtin, DeLaria, Fowler, Freeman, Gardner, Glenn, ... 1. Gary Michael Cole (born September 20, 1956) is an American actor and voice actor. Cole began his professional acting career ... Modern Family, season 1/season 2 (2010): Bowen, Burrell, Ferguson, Gould, Hyland, O'Neill, Rodriguez, Stonestreet, Vergara, ...
March 2004). "The cyclooxygenase isozyme inhibitors parecoxib and paracetamol reduce central hyperalgesia in humans". Pain. 108 ... 8 (1): 51-7. doi:10.2165/00126839-200708010-00005. PMID 17249849.. *^ Vorobeychik Y, Chen L, Bush MC, Mao J (September 2008). " ... Prostaglandins E and F are largely responsible for sensitizing the nociceptors.[1] Temporary increased sensitivity to pain also ... The release of proinflammatory cytokines such as interleukin-1 by activated leukocytes triggered by lipopolysaccharides, ...
Laverne Cox. *Lee Ae-ran. *Leopold I of Belgium. *Lil Pump. *List of active volcanoes ...
2 million[1]. White Hunter Black Heart is a 1990 American adventure drama film directed by and starring Clint Eastwood and ... White Hunter Black Heart's gross theatrical earnings reached just over $2 million, well below the film's $24 million budget.[1] ... Rosenbaum, Jonathan (December 1, 2009). "A Free Man". Retrieved 2015-01-04.. ...
Been JV, Nurmatov UB, Cox B, Nawrot TS, van Schayck CP, Sheikh A (May 2014). "Effect of smoke-free legislation on perinatal and ... 30 (1): 31-34. doi:10.1093/ije/30.1.31. PMID 11171846.. *^ Clough JD, Lewis EJ, Lachin JM (1996). "Treatment protocols of the ... 18 (1): 63-5. doi:10.1093/eurpub/ckm054. PMID 17569698.. *^ Lister, David (27 February 2007). "Rural pubs will suffer from ... Retrieved 1 March 2017.. *^ Romaniello, Matthew P.; Starks, Tricia (2009). "Tabak: An Introduction". In Romaniello, Matthew; ...
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Cox/flexion-distraction (a gentle, low-force adjusting procedure which mixes chiropractic with osteopathic principles and ... ISBN 0-07-137534-1.. *^ a b c d e f g h i Nelson CF, Lawrence DJ, Triano JJ, Bronfort G, Perle SM, Metz RD, Hegetschweiler K, ... ISBN 0-07-137534-1.. *^ a b c d e Singh, S; Ernst, E (2008). "The truth about chiropractic therapy". Trick or Treatment: The ... ISBN 0-07-137534-1.. *^ a b c d e Mootz RD, Phillips RB (1997). "Chiropractic belief systems". In Cherkin DC, Mootz RD. ...
Tom A. Williams, Peter G. Foster, Tom M. W. Nye, Cymon J. Cox, T. Martin Embley. A congruent phylogenomic signal places ... ISBN 1-55963-227-5. (ang.) *↑ a b Lech Ryszkowski: Globalisation and Biodiversity Protection (ang.). 2006. [zarchiwizowane z ... Szacunki dotyczące liczby gatunków w obrębie tej grupy wahają się pomiędzy 5 a 10 mln[1][2]. Według analiz przeprowadzonych ... Choć zmienność rozmiarów i jednych i drugich jest bardzo duża (najmniejsze eukarioty mają rozmiar mniejszy niż 1 µm), typowe ...
1920 (San Francisco): Cox/Roosevelt. *1924 (New York): J. Davis/C. Bryan ... He would grow red in the face, pound his desk, gesture wildly, and stamp his feet.[1] As Franklin Roosevelt's New Deal "marshal ... Wedded to his job, he arrived early each day, stayed late, and studied legislation at home.[1] ...
Cox, Lisa (12 March 2019). "'Almost certain extinction': 1,200 species under severe threat across world". ... 163: 1-6. doi:10.1016/j.biocon.2013.04.020.. *^ a b Lions, tigers, big cats may face extinction in 20 years by Dan Vergano, USA ... 978-1-944869-01-4. .. *^ Harvey, David (2005). A Brief History of Neoliberalism. Oxford University Press. p. 173. ISBN 978- ... September 1, 2016.. *^ This Is the Most Important Issue That's Not Being Talked About in This Election. Esquire. November 7, ...
ISBN 1-85306-590-0. pages 165-177 *^ Davies, Les (March 2009). "Starfish and subterfuge". Mendip Times. Retrieved 24 February ... The shortest route of ascent goes from the Burrington Combe car park and is approximately 1 km long. ...
... haplotype (Also: AH8.1, COX,[1] Super B8, ancestral MHC 8.1[2] or 8.1 ancestral haplotype[3]) is a multigene ... 22 (1): 59-65. doi:10.3109/08916939508995300. PMID 8882423.. *^ Mackay IR, Morris PJ (October 1972). "Association of autoimmune ... In type 1 diabetes both DR3 and DQ2 appear to play a role. DR3-DQ2.5 can be established to other genes like TNF-305A (TNF2) ... In addition the BAT1 and MICB variant is more common in type 1 diabetes when B8 is absent but DR3 is present[10] These studies ...
Boris, A.; Scott, J. W.; DeMartino, L.; Cox, D. C. (1973). "ENDOCRINE PROFILE OF A NONSTEROIDAL ANTIANDROGEN N-(3,5-DIMETHYL-4- ... 90-. ISBN 978-1-4557-2758-2.. *^ a b c d e f g h i William Figg; Cindy H. Chau; Eric J. Small (14 September 2010). Drug ... 1: S17-26. doi:10.1007/s00432-006-0133-5. PMID 16845534.. *^ a b c d e f g h Lieberman R (2001). "Androgen deprivation therapy ... 952-. ISBN 978-1-60913-713-7.. *^ a b c d e f g h Singh SM, Gauthier S, Labrie F (2000). "Androgen receptor antagonists ( ...
a b Cox, T., & Tisserand, M. (2006). Editorial: Work & Stress comes of age: Twenty years of occupational health psychology. ... 1] *^ a b Everly, G.S., Jr. (1986). An introduction to occupational health psychology. In P.A. Keller & L.G. Ritt (Eds.), ... Journal of Occupational and Environmental Medicine, 39(1), 44-50. *^ a b LaMar W.J., Gerberich, S.G., Lohman, W.H., Zaidman, B ... Work & Stress, 20, 1-5. doi:10.1080/02678370600739795 *^ a b c Barling, J., & Griffiths, A. (2011). A history of occupational ...
Kosman, D.; Mizutani, C. M.; Lemons, D; Cox, W. G.; McGinnis, W; Bier, E (2004). "Multiplex Detection of RNA Expression in ... 97 (1): 93-103. doi:10.1038/labinvest.2016.121. PMID 27892928.. *^ a b Sarrate, Z.; Vidal, F.; Blanco, J. (2010). "Role of ... 978-1-4577-1589-1. . PMID 22256298.. *^ Dill, K.; Hui Liu, R.; Grodzinski, P. (2008). Microarrays: Preparation, Microfluidics, ... 7 (1): e29923. Bibcode:2012PLoSO...729923L. doi:10.1371/journal.pone.0029923. PMC 3254647. PMID 22253826.. ...
Cyclooxygenase 2 inhibitors. *Dipeptidyl peptidase-4 inhibitors. *Direct thrombin inhibitors. *Direct Xa inhibitors ... 300 (1): 2-8. doi:10.1124/jpet.300.1.2. PMID 11752090.. *^ Perrais D, Ropert N (Jan 1999). "Effect of zolpidem on miniature ... 52: 1-32. PMID 9238846.. *^ Rupprecht R, Reul JM, Trapp T, van Steensel B, Wetzel C, Damm K, Zieglgänsberger W, Holsboer F (Sep ... 1 (4): 276-280. doi:10.1016/S1522-8401(00)90040-5.. *^ Möhler H, Fritschy JM, Rudolph U (Jan 2002). "A new benzodiazepine ...
Cox, Michael; Nelson, David (2008). Principles of Biochemistry. Susan Winslow. பக். 288. பன்னாட்டுத் தரப்புத்தக எண்: ... இருவகைக் கருவமிலங்களின் சுருளமைப்பையும், அவற்றில் உப்பு மூலங்களின் பிணைப்புக்களையும் எடுத்துக் காட்டும் படம்[1][2] ...
Cox, G. (2003). "Adverse effects of khat: a review". Advances in Psychiatric Treatment. 9 (6): 456-63. doi:10.1192/apt.9.6.456. ... "Archived from the original on 1 December 2009.. *^ a b c d e f g h i j k l m n o p q r s t u v w x Al Zarouni, Yousif (2015). ... Retrieved 1 December 2017.. *^ Gatter, Peer (2012). Politics of Qat - The Role of a Drug in Ruling Yemen. Ludwig Reichert ... ISBN 978-1-84619-093-3.. *^ a b Warfa, N.; Klein, A.; Bhui, K.; Leavey, G.; Craig, T.; Alfred Stansfeld, S. (2007). "Khat use ...
Bengal has a recorded history of 1,400 years.[1] The Bengali people are its dominant ethnolinguistic tribe. The region has been ...
Retrieved 1 December 2018.. *^ Harrad, Kate, ed. (2016). Purple Prose: Bisexuality in Britain. Thorntree Press LLC. ISBN ... Discrimination against asexual people, also known as acephobia[1][2][3] or aphobia,[4][5][6] encompasses a range of negative ... Retrieved 1 December 2018.. *^ Miri Mogilevsky (21 January 2016). "5 Things You Can Do Right Now to Support the Asexual Youth ... Retrieved 1 December 2018.. *^ Sally Goldfarb (2016). "Divorcing Marriage from Sex: Radically Rethinking the Role of Sex in ...
Cox, Brian, 1968- (2009). Why does E=mc2 : (and why should we care?). Forshaw, J. R. (Jeffrey Robert), 1968-. Cambridge, MA: Da ... To uphold causality, Minkowski restricted spacetime to non-Euclidean hyperbolic geometry.[1][page needed] ... If using a system of units where the speed of light in vacuum is defined as exactly 1, for example if space is measured in ... This page was last edited on 1 August 2020, at 21:25 (UTC). ...
Hackett, S. J.; Kimball, R. T.; Reddy, S.; Bowie, R. C. K.; Braun, E. L.; Braun, M. J.; Chojnowski, J. L.; Cox, W. A.; Han, K.- ...
If you know of any papers that use this antibody, please contact us at antibodies [at] alzforum [dot] org for consideration in the References section.. ...
Coxs Bazar-1 is a constituency represented in the Jatiya Sangsad (National Parliament) of Bangladesh since 2019 by Jafar Alam ... "Coxs Bazar-1". The Daily Star. Retrieved 31 December 2018. "Constituency Maps of Bangladesh" (PDF). Bangladesh Election ... Chittagong and Coxs Bazar. Mohammed Ellias was elected unopposed in the 2014 general election after opposition parties ...
The Cox-Klemin XA-1 was a 1920s American air ambulance biplane designed and built by the Cox-Klemin Aircraft Corporation for ... The XA-1 was a biplane powered by a 420 hp (313 kW) Liberty 12A engine with a fixed conventional landing gear, it had a crew of ... The XA-1 was designed as an ambulance aircraft to replace modified de Havilland DH.4 aircraft with the United States Army Air ... Two prototype aircraft designated XA-1 (A-1 was the first allocation in the army air services ambulance designation system) ...
Cyclooxygenase 1 antibody (ab23858). Please let us know if you have used this product in your publication ...
Cyclooxygenase 1 antibody validated for WB, IP and tested in Human, Shp and Cow. Immunogen corresponding to synthetic peptide ... Anti-COX1 / Cyclooxygenase 1 antibody. See all COX1 / Cyclooxygenase 1 primary antibodies. ... Prostaglandin H2 synthase 1 antibody. *Prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) ...
... by amidation presents a promising strategy for designing novel cyclooxygenase (COX)-2-selective inhibitors. A series of alpha- ... by amidation presents a promising strategy for designing novel cyclooxygenase (COX)-2-selective inhibitors. A series of alpha- ... Comparative studies revealed that the R- and S-enantiomers of the alpha-substituted analogs inhibit COX-2 with almost equal ... Mutagenesis studies have not been able to identify residues that manifest the enantioselectivity in COX-1. In an effort to ...
Alan Cox: Linux kernel 2.4.1-ac12. Feb 13, 2001, 23:44 (1 Talkback[s]) ... Date: Tue, 13 Feb 2001 23:39:11 +0000 (GMT) From: Alan Cox [email protected] To: [email protected] Subject: ... Alan Cox [email protected] Red Hat Kernel Hacker & Linux 2.2 Maintainer Brainbench MVP for TCP/IP ... 2.4.1-ac4 o Fix sk_in use counting in svcsock.c (Neil Brown) , Not yet a complete and final agreed solution o Add support for ...
Cox. The opening game of the Stanley Cup final was a victory for those who love hockey filled with speed, excitement, mistakes ... And Game 1 sure delivered.. Beyond that, the NHL and the NHL Players Association are looking at organizing a World Cup for ... And the Rangers? They got to the Cup final by virtue of a defensively perfect 1-0 triumph in the final game of the Eastern ... New York Rangers winger Rick Nash, right, skates around Kings defenceman Willie Mitchell during the first period of Game 1 in ...
Haley Pierson-Cox is the ideal craft crush. She combines photography skills with excellent writing to make satin tap pants look ... Haley Pierson-Cox is the ideal craft crush. She combines photography skills with excellent writing to make satin tap pants look ... 1. I have a growing pile of skirts/slips with 26″ hips, due to a design mistake that, apparently, I am destined to make over ... 1. A notebook. I love lists, so I always carry a notebook around. I find that writing something down is a necessary first step ...
"Cyclooxygenase 1" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical Subject ... COX-1 mediates IL-33-induced extracellular signal-regulated kinase activation in mast cells: Implications for aspirin ... Cyclooxygenase-1 and -2 Play Contrasting Roles in Listeria-Stimulated Immunity. J Immunol. 2018 06 01; 200(11):3729-3738. ... This graph shows the total number of publications written about "Cyclooxygenase 1" by people in Harvard Catalyst Profiles by ...
... FASEB J. 2016 Dec;30(12):4256-4266. ... Francesca Rauzi 1 , Nicholas S Kirkby 1 2 , Matthew L Edin 3 , James Whiteford 1 , Darryl C Zeldin 3 , Jane A Mitchell 2 , ... Because the effective doses of aspirin are consistent with the inhibition of cyclooxygenase-1 in platelets, we used liquid ... These results reveal 15(S)-HETE as a major platelet cyclooxygenase-1 product with strong proangiogenic effects. Thus, 15(S)- ...
COX-2(−/−), anti-COX-2. (C) COX-1(+/+)/COX-2(+/+), anti-COX-1; (Inset) epidermis of COX-1(+/+)/COX-2(+/+), anti-COX-1. (Scale ... As expected, COX-2 expression was not detected in the DA of COX-2-deficient mice (Fig. 3B). Analysis of wild-type mice with an ... COX-dependent DA closure in neonatal mice. The DA was analyzed in pups 5 h after birth. (A) COX-1(+/+)/COX-2(+/+). (B) COX-1 ... COX-2(+/+), anti-COX-2; (Inset) perinuclear staining. (B) COX-1(+/+)/ ...
Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2 [ ... Therapeutic use of cyclooxygenase-inhibiting (COX-inhibiting) nonsteroidal antiinflammatory drugs (NSAIDs) is often complicated ... cyclooxygenase 2 (COX2); cyclooxygenase-2-selective selective inhibitors (COXIBs); prostaglandin H2 (PGH2); thromboxane A2 (TxA ... Opposite effects of cyclooxygenase-1 and -2 activity on the pressor response to angiotensin II. Zhonghua Qi,1 Chuan-Ming Hao,1 ...
Chronic inhibition of COX-2 during gestation does not result in fetal DA constriction. Analysis of fetal DA on day 15 of ... COX-2-selective inhibitor SC-236. (. c. ) Chronic administration (on gestation days 15-18) of SC-236 and fetal analysis 4 hours ... Cyclooxygenase-1-selective inhibition prolongs gestation in mice without adverse effects on the ductus arteriosus. ... Cyclooxygenase-1-selective inhibition prolongs gestation in mice without adverse effects on the ductus arteriosus. ...
Cyclooxygenase-1. C O N Co3+. This is the human cyclooxygenase-1 protein (Cox-1). Cox-1 is colored to show alpha helices in red ... Acetylation of Cox-1 (or Cox-2) irreversibly inactivates the enzyme. Thats how aspirin works. Biology Home Page ... to reset the view of Cox-1. If you zoom in some, you will see arachidonic acid (gray structure surrounded with dots made of ... that is bound inside the active site of Cox-1. The two red atoms on arachidonic acid are oxygen. Notice the protoporphyrin IX ...
Cox Cervical Spine Certification Seminar in Fort Wayne, IN, 14 CE hrs - plus EXAM offered. PLEASE ENTER YOUR PERSONAL ... CLICK HERE for a study guide for the Cox Certification Examination. Haven Innovation is providing a brand new Cox8 Table for ... Cox Technic Complete (CTC) Subscribers: Congratulations! We are pleased to offer the seminar discount! Your status as a ... JULIE COX-CID F/D Enterprise LLC 260-637-6609 or 800-441-5571 [email protected] ...
... not COX-2 - might lead to a way to prevent and treat the most common and fatal form of ovarian cancer. ... Researchers at Vanderbilt University Medical Center in a new report say that blocking the COX-1 enzyme - ... as previous studies have linked high levels of another cyclooxygenase enzyme, COX-2, to colorectal and other cancers. ... Blocking the COX-1 enzyme might be the answer in ovarian cancer treatment. *Download PDF Copy ...
The cyclooxygenase-2 (COX-2) enzyme catalyzes the rate-limiting step of prostaglandin formation in inflammatory states, and COX ... 2 B). Blockade of COX-2 activity with the COX-2 inhibitor NS-398 left trace levels of PGE2 in both cell lines. To determine if ... B) COX-2 transcription was determined using a luciferase reporter construct containing either the COX-2 promoter (filled bars) ... 3 A). In addition, a reporter construct containing a 1.8-kb fragment of the COX-2 promoter demonstrated similar levels of COX-2 ...
... Haiping Wang,1 Zhanjun Jia,2 Jing ... The renal COX-2 and mPGES-1 mRNAs and their respective proteins expression, together with the renal PGE2 amounts, were induced ... IL-1. , MCP-1, ICAM-1, and VACAM-1 mRNA levels were higher in the cisplatin-treated mice, compared with the controls, but they ... 1Department of Nephrology, Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan, Shandong 250013, ...
Ratio of COX-2 expression to MUC1 expression. COX-2, cyclooxygenase-2; MUC1, mucin 1. ... Survival analysis in reference to the level of COX-2 expression. COX-2, cyclooxygenase-2 ... was considered to demonstrate a high expression of COX-2. COX-2, cyclooxygenase-2. ... These were: Anti-COX-2 rabbit monoclonal antibody from Abcam (clone SP21, cat. no. ab16701) and anti-COX 2 mouse monoclonal ...
LONGER ODDS AGAINST COX.; Senator Harding Now 2 to 1 Favorite In Wall Street. ... Archives,LONGER ODDS AGAINST COX.; Senator Harding Now 2 to 1 Favorite In Wall Street. ...
Cyclooxygenase 1 from sheep has been used as positive control protein in western blot analysis of osteoarthritis samples and in ... Biochemicals and Reagents, Cell Biology, Cell Signaling Enzymes, Cell Signaling and Neuroscience, Cyclooxygenase (COX) Enzymes ... Cyclooxygenase 1 from sheep glycerol solution, ≥1500 units/mg protein Synonym: COX-1, Constitutive cyclooxygenase, ... Cyclooxygenase 1 from sheep has been used as positive control protein in western blot analysis of osteoarthritis samples and in ...
COX. cyclooxygenase. DC. dendritic cell. LTB4. leukotriene B4. mPGES1. microsomal PG synthase E1. NIH. National Institutes of ... Taken together, our results suggest that COX-2 is necessary for optimal CD8+ T cell responses to L. monocytogenes, whereas COX- ... This phenotype was due to inhibition of the inducible COX-2 enzyme, as treatment with the COX-2-selective inhibitor celecoxib ... Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) activity and are commonly used for pain relief and ...
We have recently reported that cyclooxygenase (COX)-2-deficiency affects brain upstream and downstream enzymes in the ... with basal PGE2 production being metabolically coupled with COX-2 and TXB2 production being preferentially linked to COX-1. ... P. Li, J. Lu, C. Kaur, V. Sivakumar, K.L. Tan, E.A. Ling, Expression of cyclooxygenase-1/-2, microsomal prostaglandin-E ... The mechanism of NF-κB activation in the COX-1-/- mice involved the up-regulation of protein expression of the p50 and p65 ...
Courteney Cox has been offered a cool million to become the new face of, a website dedicated to hooking up ... Courteney Cox has been offered a cool million to become the new face of, a website dedicated to hooking up ... offers Courteney Cox $1 Million. Lydia Harris , October 13, 2010 , News , No Comments ... But theres a catch - CL would reserve the right to fire Cox if she gets arrested or "conducts herself in a manner that brings ...
3. Cox-2 inhibitor (n.). an anti-inflammatory drug that fights pain and blocks Cox-2 activity without impeding the activity of ... 8. Cox (n.). either of two related enzymes that control the production of prostaglandins and are blocked by aspirin ... 5. Cox-2 (n.). an enzyme that makes prostaglandins that cause inflammation and pain and fever ... 7. cox (n.). the helmsman of a ships boat or a racing crew ... Cox-1 (n.). an enzyme that regulates prostaglandins that are ...
Call Catherine Cox Boenitz, DDS today to schedule your next dentist appointment. ... Catherine Cox Boenitz, DDS is a trusted 1-800-DENTIST® dentist in Waco. ... Copyright © 2018 1-800-DENTIST. All rights reserved , 1-800-DENTIST® , 1-855-780-0880 , Privacy Statement , Terms and ... is my phone number and consent to receive phone calls and text messages regarding my personalized free dentist match from a 1- ...
Analysis of Cox-2 RNA by Northern blotting demonstrated that Cox-2 mRNA levels closely reflected the changes observed in Cox-2 ... a selective Cox-2 inhibitor. DFU has at least a 1000-fold specificity for Cox-2 relative to Cox-1 in tissue culture cells (54) ... Cox-2 is an inducible isoform of prostaglandin synthase (38) . Thus, one predicted functional consequence of Cox-2 up- ... 42 ), who found that intestinal polyposis in Apc mutant mice was markedly reduced by genetic ablation of Cox-2. However, Cox-2 ...
2005) Cyclooxygenase 2 (COX-2) inhibition increases the inflammatory response in the brain during systemic immune stimuli. J ... 2002) COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, ... Staining for the inducible COX-2 isoform of the same LPS-challenged mice was not qualitatively affected by COX-1 deficiency ( ... 2003) compared the effects of selective COX inhibitors on LPS-induced fever and CNS activational profiles, finding that COX-1 ...
... and COX-2. Aspirin impairs the biosynthesis of all prostanoids through the irreversible inhibition of both COX isoforms. Long- ... Inhibition of the COX-1/TXA2 pathway in platelets decreased aggregation of platelets on tumor cells, endothelial activation, ... Here, we have shown that aspirin dramatically reduced lung metastasis through inhibition of COX-1 while the cancer cells ... Aspirin blocks formation of metastatic intravascular niches by inhibiting platelet-derived COX-1/thromboxane A2. ...
  • Because the effective doses of aspirin are consistent with the inhibition of cyclooxygenase-1 in platelets, we used liquid chromatography with tandem mass spectrometry analyses and immunoassays of human platelet releasates coupled with angiogenesis assays to search for the mediators of these effects. (
  • Chronic inhibition of COX-2 during gestation does not result in fetal DA constriction. (
  • Sudhansu K. Dey, Ph.D., senior author of the paper and director of the Division of Reproductive and Developmental Biology in the Vanderbilt Department of Pediatrics says they are surprised by the results which show that COX-1 inhibition slowed the growth of ovarian tumours in mice with the disease, as previous studies have linked high levels of another cyclooxygenase enzyme, COX-2, to colorectal and other cancers. (
  • These findings, coupled with recent evidence demonstrating the benefits of COX-2 inhibitors in many cancer models, underscore the significance of aberrant COX-2 expression and suggest that pharmacologic inhibition of COX-2 and/or regulation of its expression may limit cancer progression. (
  • In summary, the pretreatment with OA-NO 2 remarkably ameliorated the cisplatin-induced kidney injury in mice, possibly via the inhibition of the inflammatory response, associated with the COX-2/mPGES-1/PGE 2 cascade. (
  • This phenotype was due to inhibition of the inducible COX-2 enzyme, as treatment with the COX-2-selective inhibitor celecoxib similarly inhibited the development of immunity. (
  • Aspirin impairs the biosynthesis of all prostanoids through the irreversible inhibition of both COX isoforms. (
  • Here, we have shown that aspirin dramatically reduced lung metastasis through inhibition of COX-1 while the cancer cells remained intravascular and that inhibition of platelet COX-1 alone was sufficient to impair metastasis. (
  • Inhibition of the COX-1/TXA2 pathway in platelets decreased aggregation of platelets on tumor cells, endothelial activation, tumor cell adhesion to the endothelium, and recruitment of metastasis-promoting monocytes/macrophages, and diminished the formation of a premetastatic niche. (
  • Despite COX-2 induction in the cerebral blood vessels of tumor-bearing mice, a selective COX-2 inhibitor had no effect on the anorexia, whereas selective COX-1 inhibition delayed its onset. (
  • Tumor growth was associated with robust increase of PGE 2 levels in plasma - a response blocked both by non-selective COX-inhibition and by selective COX-1 inhibition, but not by COX-2 inhibition. (
  • 9 ), the effect of specific pharmacological COX2 inhibition may yield critical physiological information regarding the determinants of renal hemodynamic function in humans with uncomplicated type 1 diabetes ( 13 , 14 ). (
  • Accordingly, we assessed the impact of inhibition of COX2 activity on renal hemodynamic function in a group of normotensive, normoalbuminuric adolescents and young adults with type 1 diabetes. (
  • To develop a single drug inhibiting COX-2 and PI3K/Akt signaling (and increasing MAPK pathway activity to inhibitory levels as a result of Akt inhibition), a selenium-containing glutathione (GSH) analogue of celecoxib, called selenocoxib-1-GSH was synthesized. (
  • Selenocoxib-1-GSH reduced development of xenografted tumor by approximately 70% with negligible toxicity by targeting COX-2, like celecoxib, and having novel inhibitory properties by acting as a PI3K/Akt inhibitor (and MAPK pathway activator to inhibitory levels due to Akt inhibition). (
  • The mechanism whereby NSAIDs inhibit granulation tissue angiogenesis is unknown but may involve inhibition of either or both COX isoforms (COX-1 and COX-2). (
  • 1 Inhibition of endogenous gastric mucosal PG synthesis by non-steroidal anti-inflammatory drugs (NSAIDs) is thought to underlie the ulcerogenic activity of such drugs and administration of exogenous PGs protects gastric mucosa from a variety of insults in animal models. (
  • In contrast, the acceleration rate of COX-1 is followed by inhibition upon the addition of phenol above 0.3 mM, 24 indicating that the kinetics of AA oxidation might be much more complicated for COX-1. (
  • In vivo and in vitro gene profiling, together with chromatin immunoprecipitation analysis of macrophages, revealed direct activation of the proinflammatory factor cyclooxygenase-2 and indirect inhibition of the anti-inflammatory factor arginase-1 by c-Jun. (
  • Because inhibition of Cox-2 suppresses tumor growth in several animal models, we studied expression of Cox-2 and effect of a selective Cox-2 inhibitor celecoxib in gastrointestinal tissues of the TFF1-deficient mice. (
  • Our data show that Cox-2 is expressed in gastric adenomas of the TFF1 −/− mice and suggest that inhibition of Cox-2 disturbs the integrity of the adenoma by promoting ulceration and inflammation. (
  • 10. The method of claim 1, wherein inhibition of said lipoxygenase is accomplished while maintaining gastric mucosal integrity. (
  • COX-2 inhibition also decreased Sp1-DNA complex formation and inhibited cell invasion. (
  • We identified the basal promoter region of CRMP-1 and found that COX-2 inhibition stimulates CRMP-1 transcription by modulating the interaction of the transcriptional regulatory elements, Sp1 and C/EBPα, at the promoter region of CRMP-1 , and thereby suppresses cancer cell invasion in human lung cancer cells. (
  • 2001), and is highly expressed in a variety of human cancers and cancer cell lines (Liao and Milas 2004).COX-2 overexpression is associated with more aggressive biological tumor behaviors (Liao and Milas 2004), and the inhibition of COX-2 has been regarded as an effective anticancer strategy (Davies et al. (
  • We examined whether competitive enzyme kinetics describe COX-1 inhibition by aspirin and HAPR and if they are compatible with results obtained experimentally. (
  • Enzyme kinetic modelling predicted that only low- and medium-affinity NSAIDs (Ki ≥1 μM), but not high-affinity NSAIDs, interfere with COX-1 inhibition by aspirin. (
  • Experimental results confirmed the model by showing that low or medium-affinity COX-1 inhibitors piroxicam, dipyrone and celecoxib (each n=5-10) largely prevented the inhibition of aggregation and platelet TX synthesis in vitro by 30 μmol/L aspirin whereas the high-affinity COX-1 inhibitor SC560 (n=6) did not interfere with aspirin at all. (
  • Pharmacological inhibition of microsomal prostaglandin E synthase (mPGES)-1 for selective reduction in prostaglandin E 2 (PGE 2 ) biosynthesis is protective in experimental models of cancer and inflammation. (
  • Inhibition of mPGES-1 decreased PGE 2 production and increased PGF 2α and thromboxane B 2 (TXB 2 ) formation, while inhibition of COX-2 decreased the production of all three prostanoids. (
  • Inhibition of mPGES-1 increased the concentration of sphinganine and dihydroceramide (C 16:0 DhCer), while inhibition of COX-2 caused a general decrease in most ceramides, again suggesting different effects on cell death between the two inhibitors. (
  • Our results demonstrate differences in protein and lipid profiles after inhibition of mPGES-1 or COX-2 with important implications on the therapeutic potential of mPGES-1 inhibitors as adjuvant treatment in cancer. (
  • This study demonstrates that the inhibition of 5-LOX, COX-1, and COX-2 modulates the healing process of repaired rotator cuff tendons. (
  • 5 Cyclooxygenase 1 (COX-1) has been shown to be upregulated in the spinal cord after the paw incision, and intrathecal inhibition of COX-1 reduces mechanical allodynia in the mature animal. (
  • 7 Spinal COX inhibition also reduces allodynia from nerve injury. (
  • 8 In contrast to these observations in adults, the effect of COX-1 selective inhibition in reducing mechanical allodynia after paw incision does not occur in very young animals. (
  • Therefore, we hypothesized that developmental differences in response to inhibition of COX-1 are a result of developmental differences in COX-1 expression in the spinal cord in response to the pain signals from the periphery. (
  • The ratio between the concentrations required to achieve 50% inhibition of COX‑1 and COX‑2 isoform activity was found to be 73.5. (
  • Moreover, inhibition of human ovarian tumor growth in nude mice after treatment with the potent ET A R-selective antagonist ABT-627 is associated with reduced COX-2 and vascular endothelial growth factor expression. (
  • In addition, the fluorophenyl and pyridinyl amide derivatives retained the potent and selective COX-2 inhibition demonstrated with 1. (
  • DMSO inhibits human platelet activation through cyclooxygenase-1 inhibition. (
  • Inhibitory action of DMSO could be rescued by exogenous thromboxane A2 and was mediated, at least in part, by COX-1 inhibition. (
  • However, neither inhibition of epidermal growth factor receptor (EGFR) activation with the tyrosine kinase inhibitor 4-(3-chloroanilino)-6,7-dimethoxyquinazoline HCl (AG-1478) or EGFR blocking antibody nor inhibition of extracellular signal-regulated kinase/P-38 mitogen activated protein kinases with specific inhibitors blocked IL-1β stimulation of MUC5AC mucin production. (
  • Takeuchi K (2012) Pathogenesis of NSAID-induced gastric damage: importance of cyclooxygenase inhibition and gastric hypermotility. (
  • Tanaka A, Hase S, Miyazawa T, Takeuchi K (2002) Up-regulation of cyclooxygenase-2 by inhibition of cyclooxygenase-1: a key to nonsteroidal anti-inflammatory drug-induced intestinal damage. (
  • Takeuchi K, Tanaka A, Kato S, Amagase K, Satoh H (2010) Roles of COX inhibition in pathogenesis of NSAID-induced small intestinal damage. (
  • Sheng H, Shao J, Hooton EB, Tsujii M, DuBois RN, Beauchamp RD (1997) Cyclooxygenase-2 induction and transforming growth factor beta growth inhibition in rat intestinal epithelial cells. (
  • This is the first evidence that COX-2 inhibition specifically from the mesangial cells impairs renal development, and furthers our understanding of this essential stage of nephrogenesis. (
  • and (iv) 15-LOX-1 inhibition suppressed SC-236 induced apoptosis. (
  • The finding, that COX-1 inhibition slowed the growth of epithelial ovarian tumours in a mouse model of the disease, is surprising, said Sudhansu Dey, senior author of the paper. (
  • We report here that the absence of either or both COX isoforms in mice does not result in premature closure of the DA in utero . (
  • Furthermore, 100% of the mice deficient in both isoforms die with a patent DA within 12 h of birth, indicating that in COX-2-deficient mice, the contribution of COX-1 to DA closure is gene dosage-dependent. (
  • The initial reaction in the synthesis of all PGs is catalyzed by prostaglandin G/H synthase, also known as cyclooxygenase (COX), two isoforms of which have been identified. (
  • To better understand the contribution of the COX isoforms and the PGs they produce to the function of the ductus, we have generated mice with reduced expression of COX-1 and/or COX-2, as well as mice deficient in both COX isoforms. (
  • To gain a better insight into the specific roles of COX isoforms and characterize the interactions between upstream and downstream enzymes in brain AA cascade, we examined the expression and activity of COX-2 and phospholipase A 2 enzymes (cPLA 2 and sPLA 2 ), as well as the expression of terminal prostaglandin E synthases (cPGES, mPGES-1, and − 2) in wild type and COX-1 -/- mice. (
  • One of the more contentious debates centers on the involvement of inducible (COX-2) versus constitutively expressed COX-1 isoforms in generating cerebrovascular PGE 2 production and initiating downstream HPA responses to proinflammatory challenges. (
  • Two isoforms of COX are known to exist, namely a constitutive isoform, COX-1, and a mitogen inducible isoform, COX-2. (
  • In the present study, we performed ex vivo and in vivo imaging studies with 11 C-ketoprofen methyl ester and determined the contributions of the COX isoforms during the neuroinflammatory process. (
  • Beer AM, Zagorchev P, Filipova DM, Lukanov J (2017) Effects of 1,8-Cineole on the Activity of Cyclooxygenase and Cyclooxygenase 1 and Cyclooxygenase 2 Isoforms. (
  • The effect of 1,8-cineole on the activity of cyclooxygenase and its two isoforms (COX‑1 and COX‑2) were analysed and compared with the effects of indomethacin and celecoxib. (
  • Changes in the activity of COX?1 and COX?2 isoforms of cyclooxygenase were measured with Standard Kit (Cayman Chemical, USA). (
  • Structural features characteristic of nonsteroidal antiinflammatory drugs (NSAIDs) selectively acting on each of the COX isoforms are established for the first time. (
  • Here we examined the signal transduction pathway of PKC activation and the role of PKC isoforms in interleukin-1β (IL-1β)-mediated cyclooxygenase-2 (COX-2) expression in human pulmonary epithelial cell line (A549). (
  • IL-1β caused the translocation of PKC-γ but not other isoforms from cytosol to the membrane fraction. (
  • Of the PKC isoforms present in A549 cells, only activation of PKC-γ is involved in regulating IL-1β-induced responses. (
  • Peskar BM (2005) Role of cyclooxygenase isoforms in gastric mucosal defense and ulcer healing. (
  • By Western blot analysis the comparison between normal and pathologic samples, showed a constitutive expression of both COX isoforms in the spermatozoa from healthy donors, a significant increase in COX-1 and COX-2 protein levels in both varicocele and diabetic semen samples. (
  • Our transmission electron microscopic (TEM) data with immunogold analysis provide the first morphological evidence of COX isoforms particular distribution in both healthy and pathological sperm, intriguingly revealing modifications in the amount of these enzymes. (
  • In conclusion COX isoforms might play an important role in the pathogenesis and/or manteinance of infertility states and might represent a potential therapeutic targets in future strategies designed for the treatment of fertility disorders. (
  • In the present study, we observed that COX-1 and COX-2 isoforms were expressed in freshly isolated PA of healthy rabbits. (
  • We examined the hypothesis that both COX isoforms participate in 5,6-EET induced contraction of rabbit intralobar PA. (
  • Differential metabolism of 5,6-EET by COX-1 and COX-2 does not explain the primary dependence of PA contraction on COX-1 activity because 5,6-EET was metabolized similarly by both COX isoforms. (
  • Cyclooxygenase 1 from sheep has been used as positive control protein in western blot analysis of osteoarthritis samples and in prostaglandin synthase activity assay. (
  • Expression of the inducible prostaglandin synthase cyclooxygenase-2 appears critical for intestinal tumorigenesis resulting from APC mutation, suggesting that cyclooxygenase-2 might be a transcriptional target for β-catenin/Tcf complexes. (
  • Inducible vascular prostaglandin E 2 (PGE 2 ) synthesis by endothelial (ECs) and/or perivascular cells (PVCs) (a macrophage-derived vascular cell type) is implicated in the engagement of HPA and other CNS responses, by virtue of their capacity to express cyclooxygenase-2 (COX-2) and microsomal PGE 2 synthase-1. (
  • Microsomal PGE 2 synthase-1 (mPGES-1) is the dominant and best-studied terminal PGE 2 synthase in brain. (
  • Immunohistochemical localization of microsomal PGE synthase-1 and cyclooxygenases in male mouse reproductive organs. (
  • We investigated the tissue distribution and cellular localization of microsomal PGE synthase-1 (mPGES-1) and cyclooxygenase (COX)-1 and -2 in the male mouse reproductive organs. (
  • Neutralization of plasma PGE 2 with specific antibodies did not ameliorate the anorexia, and genetic deletion of microsomal PGE synthase-1 (mPGES-1) affected neither anorexia nor tumor growth. (
  • It has been shown that IRF-1-deficient cells exhibit impaired induction of several genes involved in the innate immune response, including the 2-5A synthetase ( 11 ), inducible nitric oxide synthase (iNOS [12]), and IL-12 p40 and p35 genes ( 13 ). (
  • PGs are synthesised from arachidonic acid by cyclooxygenase (COX) via the unstable prostaglandin intermediate PGH 2 , which, in turn, is converted into other PG species such as PGE 2 by the action of specific PG synthases, for example, PGE 2 synthase. (
  • NO, a highly reactive small molecule produced within mammalian cells by the enzyme NO synthase (NOS) including iNOS (inducible NOS), eNOS (endothelial NOS) and nNOS (neuronal NOS), was initially reported by Needleman's group that can activate cyclooxygenase. (
  • BACKGROUND: Prostaglandin endoperoxide synthase/cyclooxygenase (COX) is the key enzyme in gastric mucosal protection and repair but its cellular localisation in the human stomach is still unclear. (
  • We have prepared polyclonal antiserum against sheep seminal vesicle prostaglandin H synthase (also termed cyclooxygenase) which cross-reacted with human cyclooxygenase, thereby enabling us to directly determine the synthetic rate of cyclooxygenase protein and its modulation by the monokine interleukin-1 (IL-1). (
  • We hypothesize that the expression of the major PGE2 synthesis enzymes cyclooxygenases 1 and 2 (COX-1, COX-2 ) and membrane -associated PGE2 synthase (mPGES) is altered in the kidneys of rats with NDI and CDI . (
  • They are cyclooxygenase 1 (COX-1), cyclooxygenase 2 ( COX-2 ) and prostaglandin E synthase (PGES). (
  • determine the expression of cyclo-oxygenase 1 (COX-1), cyclo-oxygenase 2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) in penile and preputial normal tissue, papilloma and SCC in horses, and whether expression of these enzymes is influenced by degree of inflammation and differentiation grade. (
  • Dey says the results will establish the foundation for further studies and clinical trials using this new approach of targeting COX-1 for the prevention and treatment of ovarian cancer and suggests further studies should be conducted to determine whether aspirin and other non-steroidal anti-inflammatory drugs, which block both COX enzymes, might improve treatment of ovarian cancer. (
  • Cyclooxygenases are key enzymes in the conversion of free arachidonic acid to prostaglandins. (
  • We have recently reported that cyclooxygenase (COX)-2-deficiency affects brain upstream and downstream enzymes in the arachidonic acid (AA) metabolic pathway to prostaglandin E 2 (PGE 2 ), as well as enzyme activity, protein and mRNA levels of the reciprocal isozyme, COX-1. (
  • There was a compensatory up-regulation of COX-2, accompanied by the activation of the NF-κB pathway, and also an increase in the upstream cPLA 2 and sPLA 2 enzymes. (
  • Additionally, COX-1 deficiency can affect the expression of reciprocal and coupled enzymes, COX-2, Ca 2+ -dependent PLA 2 , and terminal mPGES-2, to overcome defects in brain AA cascade. (
  • These observations suggest that COX-enzymes, most likely COX-1, are involved in cancer-elicited anorexia and weight loss, but that these phenomena occur independently of host mPGES-1, PGE 2 and neuronal EP 4 signaling. (
  • Cyclooxygenases (Cox) are rate-limiting enzymes that initiate the conversion of arachidonic acid to prostanoids. (
  • PG endoperoxidase H synthases (PGHSs), also called cyclooxygenases (Cox), are the rate-limiting enzymes that initiate conversion of arachidonic acid to all PGs, prostacyclins, and thromboxanes ( 2 ). (
  • The S -nitrosylation detection and subsequent kinetic investigations into the arachidonic acid (AA) oxidation of COX enzymes indicate that NO S -nitrosylates both COX-1 and COX-2 in an oxygen-dependent manner, but enhances only the dioxygenase activity of COX-2. (
  • COX enzymes are important drug targets for the non-steroidal anti-inflammatory drugs. (
  • Cyclooxygenase (COX)-1 and -2 are prostanoid-synthesizing enzymes that play important roles in the regulation of neuroinflammation and in the development of neurodegenerative disorders. (
  • Licofelone is a novel anti-inflammatory drug that inhibits 5-lipoxygenase (5-LOX), as well as cyclooxygenase (COX)-1 and COX-2 enzymes, which play important roles in inducing inflammation after injuries. (
  • COX-2 inhibitors and, in part, COX-1 inhibitor blocked ET-1-induced PGE 2 and vascular endothelial growth factor release, indicating that both enzymes participate in PGE 2 production to a different extent. (
  • Indomethacin is a potent, time-dependent, nonselective inhibitor of the cyclooxygenase enzymes (COX-1 and COX-2). (
  • He added that further studies were to be conducted to determine whether aspirin and other non-steroidal anti-inflammatory drugs, which block both COX enzymes, might improve treatment of epithelial ovarian cancer. (
  • This is the human cyclooxygenase-1 protein (Cox-1). (
  • RNA binding studies, performed to identify ARE-binding regulatory factors, demonstrated binding of the translational repressor protein TIA-1 to COX-2 mRNA. (
  • The significance of TIA-1-mediated regulation of COX-2 expression was observed in TIA-1 null fibroblasts that produced significantly more COX-2 protein than wild-type fibroblasts. (
  • We previously identified an AU-rich element (ARE) within the 3′ untranslated region (3′UTR) of COX-2 mRNA that confers posttranscriptional regulation by controlling both mRNA decay and protein translation ( 4 , 5 ). (
  • The ability of this cis-acting mRNA element to regulate COX-2 protein levels and associated prostaglandin synthesis was observed in cells maintaining low to undetectable COX-2 levels ( 4 ). (
  • In contrast, AUF1/hnRNP D protein binding of the COX-2 ARE is proposed to regulate rapid mRNA decay similar to other ARE-containing transcripts ( 7 ). (
  • Thus, the relative abundance of these functionally distinct ARE-binding proteins can determine the fate of COX-2 transcript levels and impact COX-2 protein levels. (
  • We have identified the apoptosis-associated protein TIA-1 as a regulator of COX-2 expression at the posttranscriptional level. (
  • Through its ability to bind the COX-2 ARE, this RNA-binding protein acts as a translational silencer of COX-2 expression but does not affect mRNA stability. (
  • More importantly, deficiencies in TIA-1 mRNA binding are observed in colon cancer cells overexpressing COX-2 protein through increased polysome association with COX-2 mRNA. (
  • These findings suggest that misregulated association of the TIA-1 RNA-binding protein with COX-2 mRNA contributes to enhanced expression and perhaps the overall neoplastic potential of cancer cells. (
  • The present study did not confirm a direct relationship between the expressions of COX‑2 and MUC1, or between the expression of either protein and the clinicopathological features of patients, including survival. (
  • Cyclooxygenase 1 is a 71 kDa membrane bound protein predominantly present in endoplasmic reticulum. (
  • The mechanism of NF-κB activation in the COX-1 -/- mice involved the up-regulation of protein expression of the p50 and p65 subunits of NF-κB, as well as the increased protein levels of phosphorylated IκBα and of phosphorylated IKKα/β. (
  • Expression of Wnt-1 in these cells caused transcriptional up-regulation of the cyclooxygenase-2 gene, resulting in increased levels of cyclooxygenase-2 mRNA and protein. (
  • An agent simultaneously targeting the COX-2, PI3K/Akt, and mitogen-activated protein kinase (MAPK) signaling pathways that are deregulated in up to 70% of sporadic melanomas might be an effective treatment, but no agent of this type exists. (
  • In this study, we demonstrate that interferon (IFN)-γ alone or in synergy with lipopolysaccharide (LPS) or interleukin 1α induces Cox-2 expression in mouse peritoneal macrophages, which is paralleled by changes in Cox-2 protein levels and prostaglandin E 2 (PGE 2 ) release. (
  • Conversely, the absence of IRF-2 in macrophages resulted in a significant increase in both basal and inducible Cox-2 gene and protein expression as well as IFN-γ-stimulated PGE 2 release, identifying IRF-2 as negative regulator of this promoter. (
  • Cyclooxygenase-2 (COX-2), heme oxygenase (HO-1), nuclear transcription factor kappa-B (NF-κB), and mitogen-activated protein kinase (MAPK) were measured by immunoblotting. (
  • 2005. TNF-related activation-induced cytokine enhances leukocyte adhesiveness: Induction of ICAM-1 and VCAM-1 via TNF receptor-associated factor and protein kinase C-dependent NF-B activation in endothelial cells. (
  • The solution viscosity, deuterium kinetic isotope effect (KIE), and oxygen-18 KIE experiments further demonstrate that NO activates COX-2 by altering the protein conformation to stimulate substrate association/product release and by accelerating the rate of hydrogen abstraction from AA by catalytic tyrosine radicals. (
  • Transient transfections utilizing COX-2 promoter deletion constructs and COX-2 promoter constructs, in which specific enhancer elements were mutagenized, revealed that the nuclear factor-κB (NF-κB), CCAAT/enhancer binding protein (C/EBP) and activator protein-1 (AP-1), were the predominant contributors to the effects of piperine. (
  • RESULTS: COX-2 mRNA and protein were detected in gastric ulcer tissues but not in intact gastric mucosa. (
  • COX-1 mRNA and protein were detected in the intact mucosa. (
  • CONCLUSIONS: Our results showed that COX-2 protein was induced in macrophages and fibroblasts in gastric ulcers and H pylori related gastritis, suggesting its involvement in the tissue repair process. (
  • Cox-2 mRNA and protein were strongly expressed in the pyloric adenomas of the TFF1 −/− mice as detected by in situ hybridization and immunohistochemistry. (
  • Collapsin response mediator protein-1 (CRMP-1) controls neural development and axonal growth but also acts as a cancer invasion suppressor. (
  • Overexpression of Sp1 decreased CRMP-1 promoter activity and protein expression, whereas overexpression of C/EBPα produced the opposite effect. (
  • Overexpression of cyclooxygenase-2 (COX-2) decreased CRMP-1 mRNA and protein expression. (
  • We have previously identified collapsin response mediator protein-1 (CRMP-1) as a novel invasion suppressor, showing that reduced CRMP-1 expression is associated with early metastasis and poor survival in lung cancer patients ( 8 - 10 ). (
  • 2004). The COX enzyme system is composed of two isoenzymes: COX-1, the constitutive isoform, and COX-2, the inducible protein (Davies et al. (
  • Herein, we compared the effects of mPGES-1 inhibitor Compound III (CIII) with the cyclooxygenase (COX)-2 inhibitor NS-398 on protein and lipid profiles in interleukin (IL)-1β-induced A549 lung cancer cells using mass spectrometry. (
  • Furthermore, specific protein kinase A (PKA) inhibitors blocked IL-1β and PGE 2 -induced MUC5AC production. (
  • Methods Following exposure of SKGT-4 cells to DCA, protein levels of COX-2, MAPK and PARP were examined by immunoblotting. (
  • Induction of the anti-apoptotic protein COX-2 by DCA, via MAPK/AP-1 pathway appeared to balance the DCA mediated activation of pro-apoptotic markers such as PARP cleavage and DNA fragmentation. (
  • The modification of the nonselective nonsteroidal anti-inflammatory drug, indomethacin, by amidation presents a promising strategy for designing novel cyclooxygenase (COX)-2-selective inhibitors. (
  • Treatment of mice with the nonspecific COX inhibitor indomethacin impaired the generation of cell-mediated immunity. (
  • Cox-2 expression in the brain was not influenced by IL-6 deficiency, whereas indomethacin, an inhibitor of cyclooxygenases, completely inhibited induction of IL-6. (
  • For indomethacin, it is about 10 times less than that of 1,8‑cineole. (
  • The results were compared with the effects of indomethacin, an analgesic in the NSAID group that acts as a nonselective inhibitor of cyclooxygenase [ 9 ] (COX?1 and COX?2), and with the effects of celecoxib. (
  • Plots of MetaSite predictions for sites of metabolism for indomethacin and 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1 H -indol-3-yl)- N -phenethyl-acetamide ( 1 ). (
  • LC-MS/MS analysis of an incubation mixture containing indomethacin- N -phenethyl amide ( 1 ) (20 μM) and NADPH-supplemented human liver microsomes. (
  • The model compound for these studies was the phenethyl amide (1) derivative of the nonsteroidal anti-inflammatory drug (NSAID) indomethacin. (
  • For this endeavor, we chose a series of selective cyclooxygenase (COX)-2 inhibitors comprising neutral amide derivatives of the nonsteroidal anti-inflammatory drug (NSAID) indomethacin as target compounds for optimization ( Fig. 1 ) (Kalgutkar et al. (
  • Both Wnt-1 expression and APC mutation activate a common signaling pathway involving transcriptional activation mediated by β-catenin/Tcf complexes, but few targets relevant to carcinogenesis have yet been identified. (
  • Thus, both APC mutation and ectopic Wnt-1 expression can cause tumorigenesis, and this may be, at least in part, via a common signaling pathway involving β-catenin/Tcf complexes. (
  • OBJECTIVES: We evaluated cyclooxygenase-2 (COX-2) expression and the signaling pathway leading to this induction due to Cr(VI) exposure in cultured cells. (
  • We used dominant negative mutant, genetic knockout, gene knockdown, and chromatin immunoprecipitation approaches to elucidate the signaling pathway leading to COX-2 induction. (
  • We also observed that tumor necrosis factor (TNF)-α, platelet activating factor (PAF), and lipopolysaccharide (LPS) induced COX-2 and increased MUC5AC production that was blocked by celecoxib, suggesting a common signaling pathway of inflammatory mediator-induced MUC5AC production in NHTBE cells. (
  • To understand the mechanisms regulating COX-2 expression, we examined its posttranscriptional regulation mediated through the AU-rich element (ARE) within the COX-2 mRNA 3′-untranslated region (3′UTR). (
  • These findings implicate that TIA-1 functions as a translational silencer of COX-2 expression and support the hypothesis that dysregulated RNA-binding of TIA-1 promotes COX-2 expression in neoplasia. (
  • However, tight molecular regulation allows for rapid COX-2 expression and increased prostaglandin synthesis when necessary. (
  • Several lines of evidence demonstrate that unregulated COX-2 expression occurs at multiple stages in colon carcinogenesis and is important in the promotion of tumorigenesis ( 1 , 2 ). (
  • COX-2 expression is regulated through both transcriptional and posttranscriptional mechanisms ( 3 ). (
  • In contrast, stabilization of COX-2 mRNA occurs in cancer cells, implicating that loss of ARE-function promotes heightened COX-2 expression in neoplasia ( 3 , 6 ). (
  • The renal COX-2 and mPGES-1 mRNAs and their respective proteins expression, together with the renal PGE 2 amounts, were induced by the cisplatin treatment, but their initiation was reduced by OA-NO 2 . (
  • In colorectal cancer (CRC), pathological factors that correlate with negative prognosis include, among others, overexpression of cyclooxygenase‑2 (COX‑2) and abundant expression of mucin 1 (MUC1). (
  • The aim of the present study was to investigate the possible correlation between COX‑2 and MUC1 expression and to assess the correlation between their individual expression and the clinicopathological features of patients, paying particular attention to survival. (
  • The authors concluded that the intracellular tail of MUC1 participates in the activation of proapoptotic genes and indirectly upregulates COX-2 expression ( 11 ). (
  • Perhaps this could be easily observed as altered COX-2 and MUC1 expression. (
  • In CRC, where abundant expression of COX-2 occurs frequently, such a discovery might be a substantial finding from the perspective of future targeted therapy. (
  • Here, we have investigated the effect of Wnt-1 on cyclooxygenase-2 expression. (
  • Wnt-1 expression in the mouse mammary epithelial cell lines RAC311 and C57MG induces stabilization of cytosolic β-catenin and morphological transformation. (
  • Cyclooxygenase-2 thus appears to be a common downstream target for APC mutation and Wnt-1 expression. (
  • Evidence from genetic and pharmacologic studies also supports a role for the constitutively expressed COX-1 in inflammation-induced activation of the HPA axis, although histochemical evidence to support relevant localization(s) and regulation of COX-1 expression is lacking. (
  • Interestingly, COX-1 expression is enhanced in ECs of brain PVC-depleted rats, supporting an anti-inflammatory role of the latter cell type. (
  • COX-2 induction is readily demonstrable in ECs and/or PVCs after such challenges, and its expression correlates with several acute phase endpoints across a range of experimental conditions. (
  • In the male reproductive tract, the expression of mPGES-1 increased from the testis to the cauda epididymis and was highest in the vas deferens when examined by Northern blotting, RT-PCR, and Western blotting. (
  • In addition, the caput and cauda regions of the epididymis and the vas deferens in this order showed a progressive increase in the expression of COX-1 mRNA and immunoreactivity, whereas COX-2 was dominantly expressed in the vas deferens. (
  • Cyclooxygenase (Cox)-2 expression in the brain was strongly induced 1.5 h after injection of IL-1alpha, whereas IL-6 expression was observed 3 h after the injection. (
  • In this report, we show that IFN-γ works as a pivotal regulator of the Cox-2 gene, activating its expression or coactivating LPS- and IL-1α-dependent Cox-2 expression in primary murine macrophages. (
  • This regulation is dependent on the expression of IRF-1, and requires the presence of two novel ISREs that are localized in the promoter of the murine Cox-2 gene and are conserved in the human Cox-2 gene. (
  • AIMS To investigate COX expression by human gastric endothelial (HuGE) cells during angiogenesis in vitro. (
  • METHODS COX-1 and COX-2 expression by HuGE cells was investigated by western blot analysis, indirect immunofluorescence, reverse transcriptase polymerase chain reaction, and measurement of prostaglandin E 2 synthesis. (
  • COX-2 expression was induced in HuGE cells in both angiogenesis models. (
  • CONCLUSION Angiogenesis by HuGE cells in vitro was associated with induction of functional COX-2 expression. (
  • 4 Current dogma is that COX-1 is responsible for PG synthesis in normal gastric mucosa in order to maintain mucosal homoeostasis 5 and that COX-2 is expressed by normal gastric mucosa at low levels, 6 with induction of expression during ulcer healing 7 8 or following endotoxin exposure. (
  • This study evaluated its effects on the expression of intercellular adhesion molecule 1 (ICAM-1) and inflammation-related mediators in IL-1β-stimulated human lung epithelial A549 cells. (
  • The mRNA expression levels of ICAM-1 and MUC5AC were determined by real-time polymerase chain reaction. (
  • Spilanthol decreased the expression of PGE 2 , COX-2, TNF-α, and MCP-1. (
  • It also decreased ICAM-1 expression and suppressed monocyte adhesion to IL-1β-stimulated A549 cells. (
  • These results suggest that spilanthol exerts anti-inflammatory effects by inhibiting the expression of the pro-inflammatory cytokines, COX-2, and ICAM-1 by inhibiting the NF-κB and MAPK signaling pathways. (
  • 2000. Molecular mechanisms of lipopolysaccharide induced ICAM-1 expression in A549 cells. (
  • AP-1 transcription factors have been described to orchestrate inflammatory responses in macrophages, in particular by the expression of inflammatory mediators ( 5 ). (
  • Piperine inhibits PMA-induced cyclooxygenase-2 expression through downregulating NF-κB, C/EBP and AP-1 signaling pathways in murine macrophages. (
  • In the present study, we investigated the inhibitory effects of piperine on phorbol 12-myristate 13-acetate (PMA)-induced cyclooxygenase-2 (COX-2) gene expression and analyzed the molecular mechanism of its activity in murine RAW 264.7 macrophages. (
  • Piperine dose-dependently decreased PMA-induced COX-2 expression and PGE(2) production, as well as COX-2 promoter-driven luciferase activity. (
  • COX expression was detected by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and light and electron microscopic immunohistochemistry. (
  • Expression of cyclooxygenase-2 (Cox-2) is elevated in gastric adenocarcinomas and precursor lesions leading to this disease. (
  • In this study, we investigated the transcriptional regulation of CRMP-1 expression. (
  • Chromatin immunoprecipitation assays confirmed that Sp1 and C/EBPα compete for binding at the overlapping C/EBPα and Sp1 sites and reciprocally regulate CRMP-1 expression. (
  • Conversely, the COX-2 inhibitor, celecoxib, induced a dose-dependent increase in CRMP-1 expression. (
  • COX-2 inhibitors increase CRMP-1 expression by inhibiting Sp1-DNA complex formation and enhancing DNA binding of C/EBPα at the promoter. (
  • Deciphering the transcriptional regulation of endogenous CRMP-1 expression will provide insights into the complex mechanisms of cancer metastasis and assist in the design of new strategies for cancer treatment. (
  • COX-2 expression can promote lung cancer cell proliferation, invasion, and angiogenesis. (
  • In this study, we investigated the transcriptional regulation of endogenous CRMP-1 expression and explored the potential of COX-2 inhibitors to regulate the expression of the invasion suppressor gene, CRMP-1 . (
  • In both rat models, cell-type specificity of COX isoform expression during neuroinflammation was identified immunohistochemically. (
  • In addition, immunohistochemical analysis revealed that the population of activated microglia and macrophages was elevated at the early phase with COX-1 expression but not COX-2. (
  • We have identified 11 C-ketoprofen methyl ester as a COX-1-selective PET probe, and using this, we have also demonstrated a time-dependent expression of COX-1 in activated microglia and macrophages during the neuroinflammatory process in the living brain. (
  • Hexavalent chromium Cr(VI) up-regulates COX-2 expression through an NF[kappa]B/c-Jun/AP-1-dependent pathway. (
  • RESULTS: We found that Cr(VI) exposure induced COX-2 expression in both normal human bronchial epithelial cells and mouse embryonic fibroblasts in a concentration-and time-dependent manner. (
  • CONCLUSION: We demonstrate for the first time that Cr(VI) is able to induce COX-2 expression via an NF[kappa]B/c-Jun/AP-1-dependent pathway. (
  • 6 This could be a result of differences in expression of the COX-1 or it could be that the increase in COX-1 expression in the younger animals occurs to a similar extent, but does not produce hypersensitivity after incision. (
  • ET-1 significantly increases the expression of COX-1 and COX-2, COX-2 promoter activity, and PGE 2 production. (
  • The tyrosine kinase inhibitors (genistein and tyrphostin AG126) and phosphatidylcholine-phospholipase C inhibitor (D-609) prevented IL-1β-induced prostaglandin E 2 (PGE 2 ) release and COX-2 expression, whereas U-73122 (a phosphatidylinositol-phospholipase C inhibitor) and propranolol (a phosphatidate phosphohydrolase inhibitor) had no effect. (
  • The PKC inhibitors (Go 6976 and Ro 31-8220) and NF-κB inhibitor, pyrrolidine dithiocarbamate, also attenuated IL-1β-induced PGE 2 release and COX-2 expression. (
  • These results indicate that in human pulmonary epithelial cells, IL-1β might activate phosphatidylcholine-phospholipase C through an upstream tyrosine phosphorylation to elicit PKC activation, which in turn initiates NF-κB activation, and finally induces COX-2 expression and PGE 2 release. (
  • We found that IL-1β increased cyclooxygenase-2 (COX-2) mRNA expression and prostaglandin (PG) E 2 production and that the COX-2 inhibitor celecoxib suppressed IL-1β-induced MUC5AC production. (
  • Expression and localization of COX-1, COX-2 , and mPGES in IM, inner stripe of outer medulla ( ISOM ), and cortex were determined by immunoblotting and immunohistochemistry . (
  • In lithium-induced NDI , expression of COX-1, COX-2 , and mPGES was markedly decreased in IM. (
  • In ISOM and cortex , COX-1 expression was marginally reduced and mPGES expression was unaltered. (
  • COX-2 expression was undetected in ISOM and marginally increased in cortex . (
  • Dehydration of NDI rats resulted in a marked increase in COX-2 immunolabeling in IM interstitial cells , and there was no significant change in COX-1 and mPGES expression in any kidney zone . (
  • Treatment of DDAVP in BB rats for 6 days resulted in a markedly increased expression of COX-1, COX-2 , and mPGES in IM. (
  • In the cortex , there were no changes in the expression of COX-1 and mPGES, whereas COX-2 expression was decreased. (
  • These results identify markedly reduced expression of COX-1, COX-2 , and mPGES in IM in lithium-induced NDI . (
  • Furthermore, there were major changes in the expression of COX-1, COX-2 , and mPGES in rats with CDI . (
  • Because aspirin is a rather selective inhibitor of COX-1, the ability of aspirin to reduce the risk of ovarian cancer may be dependent on the level of COX-1 expression in those cells. (
  • Gene silencing and gene expression techniques were employed to knockdown or to express COX-1, respectively. (
  • Furthermore, we developed a COX-1 expressing cell line (SKCOX-1) by stably transfecting COX-1 expression vector into COX-1 negative SKOV-3 cells. (
  • Moringa leaves and extract treatments altered the COX-1 gene expression levels to near normal values. (
  • In the present study we presented the evidence of constitutive (COX-1) and inducible (COX-2) cyclooxygenase expression in healthy human sperm as well as their expression pattern associated with varicocele and DM. (
  • They show that EBF1 in the mesangial cells directs glomerular capillary branching through NFAT activation, and consequently COX-2 expression. (
  • Mice with Ebf1 deficiency in Foxd1 lineage cells shared characteristics with Ptgs2 /COX-2-insufficient models, and mechanistic investigation revealed impaired calcineurin/NFATc1 activation and decreased COX-2 expression. (
  • Conclusions The results suggest that EBF1 regulates metanephric development at the last stages of glomerular maturation through its actions in the stromal progenitor (Foxd1 + ) lineage where it mediates proper regulation of calcineurin/NFAT signaling and COX-2 expression. (
  • It has been found that expression of 15-lipoxygenase-1 (15-LOX-1) and its main product, 13- S -hydroxyoctadecadienoic acid (13- S -HODE), are decreased in human colorectal and esophageal cancers and that non-steroidal anti-inflammatory drugs (NSAIDs) can therapeutically induce 15-LOX-1 expression to trigger apoptosis in those cancer cells. (
  • These findings in CR mice correlated with reductions in Ki-67-positive cells, vascular luminal size, vascular endothelial growth factor expression, and phosphorylation and total expression of downstream mediators of the IGF-1 pathway. (
  • COX-1 and -2 were expressed primarily in PA endothelium where COX-1 expression was dense and uniform, whereas COX-2 expression was sparse and nonuniform. (
  • In this study, we describe the distribution and expression of COX-1, COX-2, and iNOS in human ocular melanoma. (
  • METHODS: Tumour differentiation grade, degree of inflammation and COX-1, COX-2 and mPGES-1 expression in 75 formalin-fixed paraffin embedded samples of penile and preputial papilloma and SCC of 68 horses were investigated by histopathology and immunohistochemistry. (
  • No correlation between expression of COX-1 or COX-2 and inflammation was found. (
  • Expression of mPGES-1 was weakly correlated with inflammation. (
  • Expression of COX-1, COX-2 and mPGES-1 was found in 42.6%, 50.7% and 96.0% of lesions respectively, but less than 1% of cells were immunopositive for COX-1 and COX-2 in 59.4% and 84.2% of cases respectively. (
  • Expression of COX-1 was moderately negatively correlated with differentiation grade, COX-2 was not correlated and mPGES-1 was poorly negatively correlated. (
  • CONCLUSIONS: Expression of COX-1 and COX-2 in penile and preputial SCC in the horse is poor and COX inhibitors may thus be of little value for prevention or treatment. (
  • Most of these, however, used antibodies to detect COX-2 expression. (
  • The aim of this study was to evaluate expression of COX-1 in renal cell carcinoma (RCC) and its prognosticvalue. (
  • Expression of COX-1 was also evaluated in 196 RCC sections and91 adjacent normal tissues with immunohistochemistry. (
  • MetaSite correctly predicted the metabolic shift from oxidation on the amide substituent to O -demethylation for these compounds, whereas rat and human microsomal stability studies and pharmacokinetic assessments in the rat confirmed that the design tactics for improving pharmacokinetic attributes of 1 had worked in our favor. (
  • Microsomal PGES-1 is more prominently expressed in well-differentiated tissue compared with poorly differentiated tissue. (
  • Cyclooxygenase-2, Asymmetric Dimethylarginine, and the Cardiovascular Hazard From Nonsteroidal Anti-Inflammatory Drugs. (
  • The role for PGs in regulation of DA tone was initially determined from the observation that nonsteroidal anti-inflammatory drugs (NSAIDs), which act by inhibiting COX ( 4 ), modulate DA tone in utero and following birth ( 1 ). (
  • Cyclooxygenase 1 mediates prostaglandin synthesis and is modulated by anti inflammatory nonsteroidal drugs. (
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) activity and are commonly used for pain relief and fever reduction. (
  • Cyclooxygenase-1 (Cox-1) is constitutively expressed in most tissues and is thought to serve in general "housekeeping" functions, and is a target for nonsteroidal therapeutic anti-inflammatory drugs (NSAIDs). (
  • We collected from the literature a structurally diverse set of 45 nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2-selective inhibitors (coxibs) with a wide range of binding affinities for COX-1. (
  • While previous studies have demonstrated that nonsteroidal anti-inflammatory drugs and selective inhibitors of COX-2 (coxibs) may prevent the proper healing of muscles and tendons, studies about bone and cartilage have demonstrated that drugs that inhibit 5-LOX concurrently with COX-1 and COX-2 may enhance tissue regeneration. (
  • Tanaka A, Araki H, Komoike Y, Hase S, Takeuchi K (2001) Inhibi-tion of both COX-1 and COX-2 is required for development of gastric damage in response to nonsteroidal antiinflamma-tory drugs. (
  • Acetylation of Cox-1 (or Cox-2) irreversibly inactivates the enzyme. (
  • Researchers at Vanderbilt University Medical Center in a new report say that blocking the COX-1 enzyme - not COX-2 - might lead to a way to prevent and treat the most common and fatal form of ovarian cancer. (
  • Whereas prostacyclin is the predominant prostaglandin found in mouse ovarian tumours, another prostaglandin, PGE2, seems to be generated in higher quantities in human ovarian cancers and suggests that it is not the particular enzyme - COX-1 or COX-2 - but downstream factors, including prostaglandins, that initiate tumour growth, says Dey. (
  • The cyclooxygenase-2 (COX-2) enzyme catalyzes the rate-limiting step of prostaglandin formation in inflammatory states, and COX-2 overexpression plays a key role in carcinogenesis. (
  • Cyclooxygenase-2 (COX-2) is an enzyme that catalyses the formation of prostaglandins and therefore participates in the regulation of the consecutive stages of inflammatory processes. (
  • Cyclooxygenase (COX) is a bifunctional enzyme exhibiting coupled peroxidase and dioxygenase activities. (
  • Though a body of evidence indicated that NO elicits up-regulation of COX activity, 13-16 a large number of reports support the idea that NO inactivates COX 17-19 or has little effect on enzyme activity under certain conditions. (
  • 20 It was suggested that the complex chemistry of NO species (NOx) and the crude enzyme preparations result in dichotomous effects with respect to COX activation by NO. 21 Nevertheless, the mechanism of NO activation has not been understood yet and more in-depth kinetic investigations into the interaction between NO and COX are urgently needed. (
  • 22 Recently, we found that the first irreversible hydrogen transfer step in COX-2 catalysis altered along with oxygen variations, 23 suggesting that the oxygen concentration has a huge impact on enzyme activity. (
  • Cyclooxygenase (COX) is the rate-limiting enzyme in the synthesis of PGs (Rao et al. (
  • Both competitive as well as non-competitive interaction at the cyclooxygenase-1 (COX-1) enzyme have been proposed. (
  • We have developed an enzyme kinetic model of the aspirin/NSAID interaction at COX-1 using mathematical modelling and have varied enzyme kinetic parameters to predict the occurrence and the extent of HAPR. (
  • Both enzyme kinetic modelling and experimental results suggest competitive antagonism of NSAID and aspirin at COX-1 as a cause for HAPR, possibly resulting in cardiovascular events. (
  • The aim of this study is to determine the extent to which 1,8?cineole influences the activity of cyclooxygenase (COX), COX?1 and COX?2 enzyme systems. (
  • These results suggest that shortly after IL-1β administration, COX1 is the major enzyme involved in the reduction of milk intake, whereas at later times COX2 is more important, paralleling its induction. (
  • The COX enzyme class has not had the most favourable coverage recently, with the FDA questioning the safety of COX-2 arthritis drugs, such as Celebrex, Vioxx and Bextra. (
  • Whilst previous studies have linked high levels of the COX-2 enzyme to colorectal and other cancers, this latest news clearly shows the class of enzyme is not entirely accountable and may even provide a target for which an effective therapy can be based upon. (
  • This suggests that it's not the particular enzyme - COX-1 or COX-2 - but downstream factors, including prostaglandins that initiate tumour growth, Dey said. (
  • Cyclooxygenase (COX) metabolizes the polyunsaturated fatty acid arachidonic acid (AA) to PGG2, a cyclic endoperoxide that also contains a hydroperoxide, which is subsequently reduced to an alcohol in the enzyme to yield PGH2. (
  • The tyrosyl radical that abstracts the 13 pro(s) hydrogen from AA to initiate the COX catalytic cycle is generated by iron-oxo derivatives in the enzyme that result from lipid hydroperoxide interaction with heme iron. (
  • The inducible isoform of cyclooxygenase, COX-2, is an immediate-early response gene not expressed constitutively in most cells. (
  • BACKGROUND Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) and cause gastric ulceration. (
  • Extrapolation of these data to human gastric ulcer angiogenesis in vivo suggests that selective COX-2 inhibitors could delay gastric ulcer healing to the same extent as traditional NSAIDs which are non-selective COX inhibitors. (
  • Targeting mPGES-1 is envisioned as a safer alternative to traditional non-steroidal anti-inflammatory drugs (NSAIDs). (
  • In contrast, the absence of only the COX-1 isoform does not affect closure of the DA. (
  • The disruption of the genes encoding COX-1 ( Ptgs1 ) ( 12 ) and COX-2 ( Ptgs2 ) ( 13 , 14 ) has also been accomplished, and these mice have provided genetic models to study the functions of each COX isoform. (
  • Although no prenatal or postnatal phenotype involving the DA was originally reported in either COX-deficient line, functional compensation of one isoform for the other may have obscured a neonatal DA phenotype. (
  • Long-term administration of aspirin leads to reduced distant metastases in murine models and clinical trials, but the COX isoform, downstream prostanoid, and cell compartment responsible for this effect are yet to be determined. (
  • Cox-2 is the inducible isoform that is upregulated by proinflammatory agents, initiating many prostanoid-mediated pathological aspects of inflammation. (
  • 6,8,9 Crystal structure studies 10,11 reveal that COX-2 has a larger substrate binding pocket than COX-1 (Fig. S1 † ), providing the structural basis for developing new isoform-specific inhibitors (COXibs). (
  • To identify the COX isoform responsible for 11 C-ketoprofen methyl ester in the brain, we examined the ex vivo autoradiography of 11 C-ketoprofen methyl ester using COX-deficient mice. (
  • you will see arachidonic acid (gray structure surrounded with dots made of mostly carbon and hydrogen) that is bound inside the active site of Cox-1. (
  • COX-1 catalyzes the conversion of arachidonic acid to prostaglandin H 2 (the first step in the biosynthesis of prostaglandins, thromboxanes, and prostacyclins). (
  • Arachidonic acid (AA), formed from membrane phospholipids by the action of phospholipase A 2 , is the principal substrate for cyclooxygenases (COXs), which catalyze the rate-limiting conversion of AA to prostaglandin H 2 (PGH 2 ). (
  • 1,2 Human COX-1 and COX-2 are two structurally homologous hemoproteins responsible for the biosynthesis of prostaglandin H 2 from arachidonic acid (AA). (
  • Cox-1, also known as the "constitutive" cyclooxygenase, is detected in almost all tissues. (
  • COX-1 mediates IL-33-induced extracellular signal-regulated kinase activation in mast cells: Implications for aspirin sensitivity. (
  • To investigate the impact of blood type, functional polymorphism (T-1676C) of the COX-1 gene promoter, and clinical factors on the development of peptic ulcer during cardiovascular prophylaxis with low-dose aspirin. (
  • In a case-control study including 111 low-dose aspirin users with peptic ulcers and 109 controls (asymptomatic aspirin users), the polymorphism (T-1676C) of the COX-1 gene promoter was genotyped, and blood type, H pylori status, and clinical factors were assessed. (
  • The C-1676T polymorphism in the COX-1 gene promoter is not a risk factor for ulcer formation during treatment with low-dose aspirin. (
  • Here we investigated if aspirin attenuates EGFR-activated ovarian cancer cell growth in a COX-1 dependent manner. (
  • On the other hand, aspirin had no effect on cell viability in COX-1 negative ovarian cancer cells. (
  • COX-1 silencing in COX-1 positive cells attenuated the inhibitory effect of aspirin on EGF-stimulated cell viability. (
  • SKCOX-1 cells were more responsive to aspirin when compared to cells transfected with empty vector, and decreased EGF-activated Akt and Erk as well as cell viability. (
  • Both of these markers were increased upon COX-2 suppression by aspirin pretreatment prior to DCA exposure. (
  • These results reveal 15(S)-HETE as a major platelet cyclooxygenase-1 product with strong proangiogenic effects. (
  • Thus, platelet-derived TXA2 orchestrates the generation of a favorable intravascular metastatic niche that promotes tumor cell seeding and identifies COX-1/TXA2 signaling as a target for the prevention of metastasis. (
  • Conclusions: Clinically relevant concentrations of DMSO impair platelet activation by a thromboxane A2-dependent, COX-1-mediated effect. (
  • Both COX-1 and COX-2 catalyze the synthesis of PGH 2 , a product required for the formation of the various biologically active PGs ( 3 ). (
  • COX-2 inhibitors can suppress cancer development by inducing apoptosis or by inhibiting prostaglandin synthesis, cell cycle progression, angiogenesis, or metastasis ( 20 - 22 ). (
  • TY - JOUR T1 - Synthesis and structure-activity relationship studies of 1,3-diarylprop-2-yn-1-ones: dual inhibitors of cyclooxygenases and lipoxygenases. (
  • Regulation of fibroblast cyclooxygenase synthesis by interleukin-1. (
  • These findings support an involvement of COX-1 in bidirectional interplay between ECs and PVCs in initiating vascular PGE 2 and downstream HPA response to proinflammatory challenges. (
  • 1 cable Modem, 32 downstream x 8 upstream DOCSIS channels, 2 downstream x 2 upstream OFDM channels. (
  • These results indicate that impairing COX-1 and COX-2 and their downstream effect by targeting ET A R can be therapeutically advantageous in ovarian carcinoma treatment. (
  • 7 ] has shown that 1,8?cineole inhibits the activity of cyclooxygenase. (
  • COX‑2 overexpression may therefore be associated with MUC1 overexpression. (
  • In CRCs overexpression of COX-2 has been shown to correlate with poor survival and metastasis ( 6 ). (
  • The overexpression of COX-2 and the overexpression of MUC1 might be related and this relationship has already been studied in pancreatic cancer ( 11 ). (
  • In addition, MUC1 has been proposed as an alternative target for blocking COX-2 overexpression ( 11 ). (
  • reported robust COX-2 overexpression in cutaneous malignant melanoma. (
  • 2013). 'Overexpression of Cyclooxygenase-1 Correlates with Poor Prognosis in Renal Cell Carcinoma', Asian Pacific Journal of Cancer Prevention , 14(6), pp. 3729-3734. (
  • Thisis the first study to reveal overexpression of COX-1 in RRC and point to use as a prognostic marker in affectedpatients. (
  • The Vanderbilt researchers used Orsulic's model to test whether celecoxib (Celebrex), a selective COX-2 inhibitor, and SC-560, an experimental drug that selectively blocks COX-1, slowed tumour growth when these cells were transplanted into mice and they found that while Celebrex had little effect, the COX-1 blocker dramatically reduced tumour growth. (
  • Celecoxib is a selective COX?2 inhibitor that is used in the treatment of degenerative joint disease, chronic polyarthritis, and ankylosing spondylitis. (
  • The COX2-selective inhibitor, celecoxib, failed to alter the response to IL-1β 30 min after administration, but low doses antagonized the effects of IL-1β at 90 to 120 min. (
  • Celecoxib also attenuated the milk intake response observed 2 h after lipopolysaccharide (LPS), and the reductions of food pellet intake and body weight induced by IL-1β and LPS in the subsequent 24 h, suggesting that the role of COX2 may be more significant biologically than that of COX1. (
  • 1 Wi-Fi modem that earned a CEC 2018 Innovation award in the smart home category. (
  • I'm Living the Life I Paint' By Sara Gilbert Frederick Featured in 2018 November/December Issue Tim Cox has gone fishing twice already this year. (
  • However, 35% of COX-2(−/−) mice die with a patent DA within 48 h of birth. (
  • We found that brain PGE 2 concentration was significantly increased, whereas thromboxane B2 (TXB 2 ) concentration was decreased in COX-1 -/- mice. (
  • We found that a normal febrile response was induced even in IL-1alpha/beta-deficient mice, indicating that production of IL-1 in the brain is not necessarily required for the response. (
  • Induction of Cox-2 was abrogated in macrophages that lack IFN regulatory factor (IRF)-1, consistent with an attenuated hepatic mRNA response in IRF-1 −/ − mice injected with LPS. (
  • Mice deficient for trefoil factor 1 (TFF1) develop a pyloric adenoma with full penetrance. (
  • Nonneoplastic gastrointestinal tissues of wild-type or TFF1 −/− mice expressed low or nondetectable levels of Cox-2. (
  • Ex vivo autoradiographic analysis of COX-deficient mice revealed a significant reduction of 11 C-ketoprofen methyl ester accumulation only in COX-1-deficient mice, not COX-2-deficient mice. (
  • Earlier studies with COX knockout (COXko) mice suggested that COX2 was more important for hypophagia than COX1. (
  • When milk intake was measured 30 to 40 min after IL-1β, COX1ko mice showed an attenuated response, whereas COX2ko mice responded more like wild-type animals. (
  • By contrast, 90 to 120 min after IL-1β COX1ko mice responded normally, whereas COX2ko mice showed only small responses. (
  • Addition of exogenous PGE 2 to NHTBE cultures also increased MUC5AC production and IL-1β-induced Muc5ac hypersecretion in tracheas from wild-type but not from COX-2-/- mice. (
  • Background We recently showed the transcription factor Early B cell factor 1 (EBF1) is essential for the last stages of metanephric development, and that mice globally deficient in EBF1 display impaired maturation of peripheral glomeruli. (
  • Deletion of COX-2 from the interstitial/mesangial lineage displayed a less severe phenotype than EBF1 deficiency in mice. (
  • Overexpressing COX-2 in the EBF1-deficient mice, however, partially restored glomerular development. (
  • Administration of a 30% CR diet for 14 weeks decreased serum IGF-1 and hindered pancreatic ductal lesion formation and dysplastic severity, relative to a higher calorie control diet, in transgenic mice overexpressing cyclooxygenase (COX)-2 (BK5.COX-2). (
  • Cell lines derived from BK5.COX-2 ductal lesions (JC101cells) formed pancreatic tumors in wild-type FVB mice that were significantly reduced in size by a 14-week CR regimen, relative to the control diet. (
  • To further understand the impact of circulating levels of IGF-1 on tumor growth in this model, we orthotopically injected JC101 cells into liver-specific IGF-1-deficient (LID) mice. (
  • The ~65% reduction of serum IGF-1 in LID mice resulted in significantly decreased burden of JC101 tumors, despite modestly elevated levels of circulating insulin and leptin. (
  • OBJECTIVE- Studies in animal models suggest that cyclooxygenase-2 (COX2) plays a role in the regulation of the renal microcirculation in diabetes. (
  • Accordingly, we examined the role of COX2 in the control of renal hemodynamic function and in the renal response to hyperglycemia in humans with uncomplicated type 1 diabetes. (
  • CONCLUSIONS- In summary, our results support the hypothesis that COX2 is an important determinant of renal hemodynamic function in subjects with type 1 diabetes. (
  • Immunofluorescent analysis of (4% PFA) fixed mouse lung tissue using COX2/ Cyclooxygenase 2/ PTGS2 antibody (66351-1-Ig, Clone: 3G2B9 ) at dilution of 1:400 and CoraLite®488-Conjugated AffiniPure Goat Anti-Mouse IgG(H+L). (
  • Untreated and LPS-treated Hela cells were subjected to SDS PAGE followed by western blot with 66351-1-Ig (COX2/ Cyclooxygenase 2 Antibody) at dilution of 1:1000 incubated at room temperature for 1.5 hours. (
  • Immunohistochemical analysis of paraffin-embedded human lung cancer tissue slide using 66351-1-Ig (COX2/ Cyclooxygenase 2 Antibody) at dilution of 1:200 (under 10x lens). (
  • Immunohistochemical analysis of paraffin-embedded human lung cancer tissue slide using 66351-1-Ig (COX2/ Cyclooxygenase 2 Antibody) at dilution of 1:200 (under 40x lens). (
  • Posttranscriptional regulation mediated by the COX-2 ARE is facilitated through trans-acting ARE-binding factors. (
  • In view of the critical role of cyclooxygenase-2 in intestinal tumorigenesis, cyclooxygenase-2 up-regulation in response to Wnt signaling may contribute to Wnt -induced mammary carcinogenesis. (
  • 2004. Role and regulation of interleukin-1 molecules in pro-asthmatic sensitised airway smooth muscle. (
  • Consistent with this, the density of COX-2 - expressing cells in macula densa was significantly increased, indicating differential regulation of COX-2 in IM and cortex . (
  • In the present study, we tested whether SC-236 induced apoptosis through up-regulation of 15-LOX-1 in gastric cancer. (
  • These findings demonstrated that SC-236 induced apoptosis in gastric cancer cells via up-regulation of 15-LOX-1, and 13- S -HODE. (
  • Their polarization and activation are controlled by transcription factors such as NF-κB and the AP-1 transcription factor member c-Fos. (
  • Surprisingly, little is known about the role of the AP-1 transcription factor c-Jun in macrophage activation. (
  • Thus, c-Jun regulates the activation state of macrophages and promotes arthritis via differentially regulating cyclooxygenase-2 and arginase-1 levels. (
  • In macrophages, AP-1 proteins can regulate inflammatory processes through activation of cytokine production. (
  • For instance, the activation of IL and TLR leads to the initiation of an MAPK signaling cascade through MyD88, resulting in the activation of AP-1 in macrophages ( 2 , 3 ). (
  • Our results show that p65 and c-Jun are two major components involved in NF[kappa]B and AP-1 activation, respectively. (
  • Activation of the endothelin A receptor (ET A R) by endothelin (ET)-1 is biologically relevant in several malignancies, including ovarian carcinoma. (
  • We conclude that the induction of MUC5AC by IL-1β, TNF-α, PAF, and LPS involves COX-2- generated PGE 2 , activation of EP2 and/or EP4 receptor(s), and cAMP-PKA-mediated signaling. (
  • Results DCA induced persistent activation of the AP-1 transcription factor with Fra-1 and JunB identified as the predominant components of the DCA-induced AP-1 complex. (
  • Their polarisation and activation are controlled by transcription factors, such as NF-κB and the AP-1 transcription factor members JunB or JunD. (
  • However, the role of the third JUN/AP-1 member, c-Jun, is still ill defined during macrophage activation in RA. (
  • Interleukin-1 (IL-1) induces hypophagia, which can be reduced by cyclooxygenase (COX) inhibitors. (
  • Cox-2, the "inducible" cyclooxygenase, is not generally expressed basally, but is rapidly and strongly activated in many cells upon induction with a variety of proinflammatory agents, cytokines, hormones, and tumor promoters ( 2 ). (
  • 13 It is established that human umbilical vein endothelial cells (HUVECs) express COX-1 constitutively and COX-2 following induction by factors such as interleukin 1 and phorbol ester in vitro. (
  • METHODS: We used the luciferase reporter assay and Western blotting to determine COX-2 induction by Cr(VI). (
  • Moreover, our studies suggest crosstalk between NF[kappa]B and c-Jun/AP-1 pathways in cellular response to Cr(VI) exposure for COX-2 induction. (
  • 2002). COX-2 can undergo rapid induction in response to many factors, such as growth factors and cytokines (Kirschenbaum et al. (
  • 2002). Thus, identification of the potential involvement of COX-2 and molecular mechanisms responsible for COX-2 induction due to Cr(VI) exposure will provide significant insight into understanding Cr(VI) lung inflammatory and carcinogenic effects. (
  • Pharmacological blockade of the ET A R is an attractive strategy to control COX-2 induction, which has been associated with ovarian carcinoma progression and chemoresistance. (
  • 2 Misoprostol (a PGE 1 analogue) prevents NSAID associated peptic ulceration and its complications in humans. (
  • Unlike the parent NSAID, 1 is a potent and selective cyclooxygenase-2 (COX-2) inhibitor and nonulcerogenic anti-inflammatory agent in the rat. (
  • Thus, this study details the development of selenocoxib-1-GSH, which is a nontoxic agent that targets the COX-2 and PI3K/Akt signaling pathways in melanomas to inhibit tumor development. (
  • Cox-1 Inhibitors offered by Santa Cruz inhibit Cox-1 and, in some cases, other prostaglandin and inflammation related proteins. (
  • The production of prostaglandins is dependent on two cyclooxygenases (COX-1 and COX-2), which are encoded by separate genes. (
  • The drug also blocked production by COX-1 of prostacyclin, a member of a family of potent, hormone-like substances called prostaglandins that play a role in a wide variety of physiological functions including pain, inflammation and, possibly cancer. (
  • Prostanoids are a large family of bioactive lipids derived from the activity of cyclooxygenase-1 (COX-1) and COX-2. (
  • Cyclooxygenase-1 and -2 Play Contrasting Roles in Listeria-Stimulated Immunity. (
  • Together, these data establish roles for COX-1, and especially for COX-2, in the transition of the cardiopulmonary circulation at birth. (
  • 1-3 They have been found to play great roles in certain diseases, including cancer, 4 and nervous system 5 and apoptosis-related diseases. (
  • Recent reports strongly imply COX-2 may play distinct roles during oncogenesis, including transformation, tumor proliferation, angiogenesis, metastasis, and immune surveillance. (
  • Likewise, because P450 3A4 and P450 2D6 are involved in the metabolism of 1 , we chose the software's ability to predict contributions from these two P450 isozymes. (
  • Based on the available P450 phenotyping information for 1 , we chose the software's ability to predict metabolism by P450 3A4 and P450 2D6 for compounds 2 and 3 and by P450 3A4, 2D6, and 2C9 for compound 4 . (
  • 2004 ) in an independent metabolism study on 1 . (
  • This pharmacological benefit is offset by the finding that 1 is very unstable in rat and human microsomes because of extensive P4503 A4/2D6-mediated metabolism on the phenethyl group, experimental observations that were accurately predicted by MetaSite. (
  • The information was used to design analogs with polar (glycinyl) and/or electron-deficient (fluorophenyl, fluoropyridinyl) amide substituents to reduce metabolism in 1. (
  • The initial research objectives were to determine by GC-MS the effect of lipid hydroperoxides contained in AA preparations on COX-dependent metabolism of AA after TPP treatment and isolation of AA by TLC, and the effect of TTP treatment on the products formed during COX metabolism of AA. (
  • COX activity assay is a colorimetrical assay of the peroxidase component of cyclooxygenases. (
  • we also investigated the activity of the COX-2 promoter by luciferase assay and the release of prostaglandin (PG) E 2 by ELISA. (
  • AP-1 activity was assessed by mobility shift assay. (
  • In contrast, IRF-2 is constitutively expressed and acts mostly as a repressor by competing with IRF-1 for the same cis-element (the ISRE has also been called IRF-1/IRF-2 binding sequence motif, or IRF-E), and possibly by repressing activators positioned nearby in the promoter ( 6 )( 7 )( 8 ). (
  • COX-1 is believed to be constitutively expressed in the body, i.e., produced constantly regardless of physiological conditions or demand. (
  • COX-1 appears to be constitutively expressed in many normal ocular structures, including ciliary epithelium, retina, optic nerve glial cells, and established vasculature. (
  • Epithelial Cells Induce a Cyclo-Oxygenase-1-Dependent Endogenous Reduction in Airway Smooth Muscle Contractile Phenotype. (
  • Colon cancer cells demonstrated to overexpress COX-2 through increased polysome association with COX-2 mRNA also showed defective TIA-1 binding both in vitro and in vivo. (
  • Two cell types of the cerebral vasculature, endothelial cells (ECs) and perivascular cells (PVCs) (a subset of brain resident macrophages) have been implicated in the transduction of circulating immune signals presented by IL-1β or LPS ( Schiltz and Sawchenko, 2002 ). (
  • By immunohistochemistry, mPGES-1 was detected in Leydig cells of the testis and in epithelial cells of the epididymis, vas deferens, and seminal vesicles. (
  • COX-1 was localized in epithelial cells of the caput, corpus and cauda epididymis and of the vas deferens, and COX-2 was evident in epithelial cells of the distal cauda epididymis and vas deferens. (
  • RESULTS Under normal culture conditions (30% serum), HuGE cells expressed COX-1 and low levels of COX-2. (
  • Prostaglandin E 2 production and tubular structure formation by HuGE cells on basement membrane matrix was significantly inhibited by a selective COX-2 inhibitor (NS-398). (
  • 9 Iseki has reported the localisation of COX-1 and COX-2 to mucous cells of normal rat gastric mucosa 10 but these data have not been confirmed by others who have been unable to detect COX-2 immunoreactivity in normal rat stomach. (
  • Capillary endothelial cells are a major site of PGE 2 production in canine fundic mucosa 12 and COX-1 has been localised to endothelium of submucosal blood vessels in rat gastric mucosa. (
  • Human lung epithelial A549 cells were pretreated with various concentrations of spilanthol (3-100 μM) followed by treatment with IL-1β to induce inflammation. (
  • The percentage of COX-2 expressing cells was significantly higher in open than in closed ulcers, and in gastritis than in gastric mucosa without H pylori infection. (
  • COX-1 immunoreactivity localised in lamina propria mesenchymal cells was similar in various stages of ulcer disease and in intact gastric mucosa. (
  • Cyclooxygenase-2 (COX-2) is overexpressed in lung cancer cells and is a prognostic marker for lung cancer ( 18 , 19 ). (
  • Ovarian cancer cells usually express high levels of cyclooxygenase-1 (COX)-1. (
  • Cyclooxygenases are important in spermatogenesis, but their ultrastructural localization in sperm cells and their role in male infertility have not yet established in humans. (
  • 1 Migrating endothelial cells and differentiating podocytes next lay down extracellular matrices that fuse to become the glomerular basement membrane (GBM). (
  • We found that a specific cyclooxygenase-2 (COX-2) inhibitor SC-236 similarly induced apoptosis in gastric cancer cells. (
  • COX-2 is sporadically and focally expressed in epithelioid areas of tumors, infiltrating cells, and vasculature adjacent to and within tumorous lesions. (
  • The aim of this study was to investigate DCA-stimulated COX-2 signaling pathways and their possible contribution to deregulated cell survival and apoptosis in esophageal adenocarcinoma cells. (
  • Conclusion DCA regulates both apoptosis and COX-2-regulated cell survival in esophageal cells suggesting that the balance between these two opposing signals may determine the transformation potential of DCA as a component of the refluxate. (
  • PGs are involved in homeostatic, developmental, and inflammatory processes ( 1 ). (
  • 2015. Anti-inflammatory deficiencies in neutrophilic asthma: Reduced galectin-3 and IL-1RA/IL-1β. (
  • Over the past decades, COX-2 inhibitors have widely been used as anti-inflammatory medicine, although they usually elicit potential cardiotoxic side effects. (
  • These findings demonstrate that piperine effectively attenuates COX-2 production, and provide further insight into the signal transduction pathways involved in the anti-inflammatory effects of piperine. (
  • The anti-inflammatory effects of 1,8‑cineole (eucalyptol) in the treatment of acute bronchitis and treatment of chronic airway diseases like asthma as well as hay fever have been observed in clinical practice for some time. (
  • In vitro studies have revealed secretomotor, expectorant, antispasmodic [ 2 , 3 ], local hyperaemic and anti-inflammatory properties [ 4 ] for naturally isolated 1,8-cineole (synonym: eucalyptol). (
  • Due to its efficacy and excellent tolerability, 1,8-cineole has been successfully used for decades for topical treatment of rheumatic disorders, as well as for oral application to treat inflammatory diseases of the respiratory tract, sinusitis , acute and chronic bronchitis and as a concomitant therapy in COPD and steroid-dependent asthma [ 5 , 6 ]. (
  • COX/5-LO-IN-1 (Atreleuton analog) is an inhibitor of cylooxygenase and 5-lipoxygenase (5-LO), used for the research of inflammatory and allergic disease states. (
  • Metabolites of arachadonic acid participate in normal and aberrant growth responses, including chronic inflammation and carcinogenesis ( 1 ). (
  • IL-1 is an endogenous pyrogen produced upon inflammation or infection. (
  • 8. The method of claim 1, further comprising the step of reducing inflammation. (
  • In the present study, we examined the impact of CR on a model of inflammation-associated pancreatitis and pancreatic dysplasia, with a focus on the mechanistic contribution of systemic IGF-1. (
  • Furthermore, Cox-2 appears critical for tumor formation resulting from APC mutation. (
  • Treatment with a non-selective COX inhibitor attenuated the anorexia, and also tumor growth. (
  • When given at manifest anorexia, non-selective COX-inhibitors restored appetite and prevented body weight loss without affecting tumor size. (
  • In this tumor, the ET-1/ET A R autocrine pathway promotes mitogenesis, apoptosis protection, invasion, and neoangiogenesis. (
  • Selective COX-2 inhibitors suppress tumor incidence, growth, and metastasis in models of human cancer. (
  • The most intense and diffuse COX-2 staining was observed in a highly aggressive tumor (≷20 mitotic figures per HPF), and in general, appears to be concentrated in proliferating margins of the tumors. (
  • The present experiments fill this void in showing that COX-1 immunoreactivity (IR) and mRNA are detectable in identified PVCs and parenchymal microglia under basal conditions and is robustly expressed in these and ECs 1-3 h after intravenous injection of LPS (2 μg/kg). (
  • Standard paraffin sections were prepared, blocked for endogenous peroxidase and avidin/biotin, placed in citrate buffer, and stained for COX-1 (#160110, Cayman Chemical), COX-2 (#PG-27, Oxford Biologicals) or iNOS (Pharmacia Corp.). Immunoreactivity was detected using the standard ABC or Envision (Dako) methods, and visualized with the purple substrate VIP (Vector Labs). (
  • COX-2 immunoreactivity was not detected in normal ocular structures. (
  • Calorie restriction (CR) prevents obesity, suppresses carcinogenesis in many models, and reduces serum levels of insulin-like growth factor (IGF)-1. (
  • Further research on the role of mPGES-1 in carcinogenesis is needed to assess its potential use as a treatment target. (
  • 8 9 11 There are no published studies of COX localisation in human gastric mucosa. (
  • Localisation of cyclooxygenase 1 and cyclooxygenase 2 in Helicobacter pylori related gastritis and gastric ulcer tissues in humans. (
  • Three dimensional quantitative structural activity relationship studies have been performed on a series of 17 compounds of 1,3,4 triaryl-3-pyrrolin-2-ones, for their cyclooxygenase-2 inhibitory activities by using the logico-structural based pharmacophore mapping approach employing APEX 3D software program. (
  • COX-2 immunostaining was exclusively localised in macrophages and fibroblasts between necrotic and granulation tissues of the ulcer bed. (
  • Electron microscopic immunohistochemistry revealed both COX-1 and COX-2 on the luminal surfaces of the endoplasmic reticulum and nuclear envelope of macrophages and fibroblasts. (
  • A significant increase in 11 C-ketoprofen methyl ester accumulation was also observed at day 1 after intrastriatal injection of quinolinic acid, with increased COX-1-expressing activated microglia and macrophages. (
  • Mucin 1 (MUC1) is a structural membrane-bound mucin that is normally present only on the apical borders of the secretory epithelium. (
  • A cell-permeable potent and selective inhibitor of COX-2 from human monocytes (IC 50 = 650 nM) and in whole blood (IC 50 = 4.3 µM). (
  • These regulatory proteins form stable complexes with the COX-2 3′UTR and regulate both COX-2 mRNA stability and translation ( 4 , 7 ). (
  • The transcription factor family AP-1 is composed of homo- and heterodimeric complexes, which consist of Jun, Fos, activating transcription factor, and musculoaponeurotic fibrosarcoma proteins. (
  • AIMS: To investigate immunohistochemically the cellular distribution of COX-1 and COX-2 proteins in the human stomach with or without gastritis or ulceration. (
  • Some metastasis-suppressing proteins, such as NM23, BRMS1, KiSS-1, and KAI1, have been identified, but their mechanisms of action have not been established ( 4 - 7 ). (
  • The Vanderbilt researchers used multiple techniques, and in 2003 reported that COX-1 was over-expressed and promoted the growth of blood vessels in human epithelial ovarian tumours. (
  • Two IFN stimulation response elements were identified in the mouse Cox-2 promoter that were highly conserved in the human Cox-2 gene. (
  • Herein, recombinant human COX-1 and COX-2 were prepared and treated with NO donors individually under anaerobic and aerobic conditions. (
  • The binding of this data set to a homology model of human COX-1 was analyzed with different combinations of molecular docking algorithms, scoring functions, and the linear interaction energy (LIE) method for estimating binding affinities. (
  • Functional involvement of COX-1 is indicated by the observation that central, but not systemic, pretreatment with the selective COX-1 inhibitor SC-560 attenuated the early phase of LPS-induced increases in adrenocorticotropin and corticosterone secretion. (
  • 12 Since then, numerous studies have shown that there is crosstalk between the NOS and COX pathways. (
  • The goal of the present study was to elucidate the signaling pathways involved in IL-1β-induced MUC5AC production. (