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    1291 results match your criteria Cyclooxygenase Deficiency

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

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

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

    Salt supplementation ameliorates developmental kidney defects in COX-2-/- mice.
    Am J Physiol Renal Physiol 2017 Mar 8:ajprenal.00565.2016. Epub 2017 Mar 8.
    Goethe-University
    Deficiency of cyclooxygenase-2 (COX-2) activity in the early postnatal time course causes impairment of kidney development leading to kidney insufficiency. We hypothesize that impaired NaCl reabsorption during the first days of life is a substantial cause for nephrogenic defects observed in COX-2-/- mice and that salt supplementation corrects these defects. Daily injections of 0. Read More

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    Deficiency in either COX-1 or COX-2 genes does not affect amyloid beta protein burden in amyloid precursor protein transgenic mice.
    Biochem Biophys Res Commun 2016 Sep 15;478(1):286-92. Epub 2016 Jul 15.
    Department of Neurosciences, University of California, San Diego, CA 92037, USA; Departments of Medicine and Physiology, National University of Singapore, Yong Loo Lin School of Medicine, Singapore, 117597, Singapore. Electronic address:
    Epidemiologic studies indicate that chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a lower risk for developing Alzheimer's disease (AD). Because the primary mode of action of NSAIDs is to inhibit cyclooxygenase (COX) activity, it has been proposed that perturbed activity of COX-1 or COX-2 contributes to AD pathogenesis. To test the role of COX-1 or COX-2 in amyloid deposition and amyloid-associated inflammatory changes, we examined amyloid precursor protein (APP) transgenic mice in the context of either COX-1 or COX-2 deficiency. Read More

    Simultaneous quantification of PGI2 and TXA2 metabolites in plasma and urine in NO-deficient mice by a novel UHPLC/MS/MS method.
    J Pharm Biomed Anal 2016 Sep 28;129:148-54. Epub 2016 Jun 28.
    Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, 30-348 Krakow, Poland; Chair of Pharmacology, Jagiellonian University, Medical College, Grzegorzecka 16, 31-531 Krakow, Poland. Electronic address:
    The balance between vascular prostacyclin (PGI2) generated mainly via cyclooxygenase-2 (COX-2) and its physiological antagonist platelet-derived thromboxane A2 (TXA2) formed by cyclooxygenase-1 (COX-1) determines cardiovascular homeostasis. In the present work, a novel bioanalytical method for simultaneous quantification of stable plasma and urinary metabolites of PGI2 (6-keto-PGF1α, 2,3-dinor-6-keto-PGF1α) and TXA2 (TXB2, 2,3-dinor-TXB2) using ultra high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC/MS/MS) was developed. The method was validated using artificial plasma and urine and linearity range, intra- and inter-day precision and accuracy, recovery of analytes, relative and absolute matrix effect and stability of analytes were determined. Read More

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

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

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

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

    Deficiency of cold-inducible ribonucleic acid-binding protein reduces renal injury after ischemia-reperfusion.
    Surgery 2016 Aug 3;160(2):473-83. Epub 2016 Jun 3.
    Department of Surgery, Hofstra Northwell School of Medicine, Manhasset, NY; Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, NY. Electronic address:
    Background: Renal ischemia-reperfusion injury, commonly caused by major operation and shock, leads to acute kidney injury and is associated with high morbidity and mortality. Cold-inducible ribonucleic acid-binding protein, a cold shock protein, has recently been identified as a damage-associated molecular pattern. We hypothesized that cold-inducible ribonucleic acid-binding protein exacerbates severity of injury in renal ischemia-reperfusion. Read More

    The Effect of PSD-93 Deficiency on the Expression of Early Inflammatory Cytokines Induced by Ischemic Brain Injury.
    Cell Biochem Biophys 2015 Dec;73(3):695-700
    Department of Neurology, Drum Tower Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
    The aim of the study was to explore the effect of PSD-93 deficiency on the expression of early inflammatory cytokines induced by cerebral ischemia/reperfusion injury. Ten- to twelve-week-old male PSD-93 knockout (PSD-93 KO) mice (C57BL/6 genetic background) and wild-type (WT) littermates were randomly divided into sham and ischemia/reperfusion (I/R) group. The focal cerebral I/R model was established by middle cerebral artery occlusion (MCAO) suture method. Read More

    Anti-proliferation effects of Cistanches salsa on the progression of benign prostatic hyperplasia.
    Can J Physiol Pharmacol 2016 Jan 18;94(1):104-11. Epub 2015 Jul 18.
    Cistanche salsa has been used in traditional medicine for the treatment of kidney deficiency, neurasthenia, sexual dysfunction diseases, and benign prostatic hyperplasia (BPH). The aim of this study was to investigate the mechanism by which C. salsa extract (CSE) elicits an anti-proliferative effect on the prostate tissue of BPH-induced rats. Read More

    Diminished COX-2/PGE2-Mediated Antiviral Response Due to Impaired NOX/MAPK Signaling in G6PD-Knockdown Lung Epithelial Cells.
    PLoS One 2016 20;11(4):e0153462. Epub 2016 Apr 20.
    Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.
    Glucose-6-phosphate dehydrogenase (G6PD) provides the reducing agent NADPH to meet the cellular needs for reductive biosynthesis and the maintenance of redox homeostasis. G6PD-deficient cells experience a high level of oxidative stress and an increased susceptibility to viral infections. Cyclooxygenase-2 (COX-2) is a key mediator in the regulation of viral replication and inflammatory response. Read More

    mTORC1-mediated downregulation of COX2 restrains tumor growth caused by TSC2 deficiency.
    Oncotarget 2016 May;7(19):28435-47
    Department of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical University, Hefei, China.
    Tuberous sclerosis complex (TSC), caused by loss-of-function mutations in the TSC1 or TSC2 gene, is characterized by benign tumor formation in multiple organs. Hyperactivation of mammalian target of rapamycin complex 1 (mTORC1) is the primary alteration underlying TSC tumors. By analyzing Tsc2-null mouse embryonic fibroblasts (MEFs) and rat uterine leiomyoma-derived Tsc2-null ELT3 cells, we detected evidence for the involvement of cyclooxygenase 2 (COX2) as a downstream target of mTORC1 in the development of TSC tumors. Read More

    Effects of BM-573 on Endothelial Dependent Relaxation and Increased Blood Pressure at Early Stages of Atherosclerosis.
    PLoS One 2016 28;11(3):e0152579. Epub 2016 Mar 28.
    Pole of Pharmacology and Therapeutics (FATH), Institute of Experimental & Clinical Research (IREC), Université Catholique de Louvain (UCL) Medical School, Brussels, Belgium.
    Endothelial dysfunction is considered to be an early event in atherosclerosis and plays a pivotal role in the development, progression and clinical complications of atherosclerosis. Previous studies have shown the beneficial effects of combined inhibition of thromboxane synthase and antagonism of thromboxane receptors by BM-573 on atherosclerosis; however our knowledge about the beneficial effects of BM-573 on endothelial function and increased blood pressure related to early stage of atherosclerosis is limited. In the present study, we investigated the effects of short-term (3 μM, 1 hour) and chronic (10 mg/L, 8 weeks) treatments with BM-573 on vasodilatory function, nitric oxide (NO) bioavailability, oxidative stress and systolic blood pressure in 15 weeks old apolipoprotein E-deficient (ApoE-KO) mice. Read More

    Thromboxane Governs the Differentiation of Adipose-Derived Stromal Cells Toward Endothelial Cells In Vitro and In Vivo.
    Circ Res 2016 Apr 8;118(8):1194-207. Epub 2016 Mar 8.
    From the Key Laboratory of Food Safety Research, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (Y.S., S.Z., Y.W., S.Y., D.C., B.X., J.Z., Y.G., M.S., J.T., D.K., L.L., Y.Y., B.Z., S.-Z.D., Y.Y.); Department of Nutrition, The NO.2 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China (Y.S., H.S.); Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie, AREA Science Park, Trieste, Italy (C.S.); Dipartimento di Scienze e Tecnologie Biomediche, Università di Udine, Udine, Italy (C.S.); and Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada (C.D.F.).
    Rationale: Autologous adipose-derived stromal cells (ASCs) offer great promise as angiogenic cell therapy for ischemic diseases. Because of their limited self-renewal capacity and pluripotentiality, the therapeutic efficacy of ASCs is still relatively low. Thromboxane has been shown to play an important role in the maintenance of vascular homeostasis. Read More

    [Efficacy Observation of Ultrasonic Conductometric Acupoint Penetration of Wenhua Zhitong Recipe for Adenomyosis Patients].
    Zhongguo Zhong Xi Yi Jie He Za Zhi 2016 Jan;36(1):54-8
    Objective: To observe the efficacy of ultrasonic conductometric acupoint penetration of Wenhua Zhitong Recipe (WZR) in treating adenomyosis.

    Methods: Totally 40 adenomyosis patients with Shen-deficiency blood stasis syndrome were randomly assigned to the treatment group and the control group, 20 in each group. Patients in the treatment group received ultrasonic conductometric acupoint penetration of WZR from the 2nd day before menstruation to the end of menstruation, while those in the control group took WZR. Read More

    Functional Role of FcγRIIB in the Regulation of Mesenchymal Stem Cell Function.
    Int J Med Sci 2016 5;13(2):154-60. Epub 2016 Feb 5.
    1. Department of Respiratory, Changhai Hospital, Second Military Medical University, Shanghai 200433, China;
    Mesenchymal stem cells (MSCs) derived from bone marrow are plural-potent stem cells with immune regulatory functions. We aimed to evaluate role of FcγRIIB in the regulation of bone marrow-derived MSC function. MSCs were prepared from mouse bone marrow derived from wild-type (WT) or FcγRIIB-deficient (FcγRIIB-/-) mice. Read More

    Selenium Deficiency-Induced Inflammation and Increased Expression of Regulating Inflammatory Cytokines in the Chicken Gastrointestinal Tract.
    Biol Trace Elem Res 2016 Sep 22;173(1):210-8. Epub 2016 Feb 22.
    College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Harbin, Hei Longjiang, 150030, People's Republic of China.
    Selenium (Se), a nutritionally essential trace element, plays an important role in various aspects of health for a wide range of species, including birds. Se deficiency inhibits the growth of immune organs and decreases immune function, leading to many inflammatory diseases. The present study determined the effects and mechanism of dietary Se deficiency on gastrointestinal tract tissue inflammation. Read More

    Is the cardiovascular toxicity of NSAIDS and COX-2 selective inhibitors underestimated in patients with haemophilia?
    Crit Rev Oncol Hematol 2016 Apr 12;100:25-31. Epub 2016 Feb 12.
    Haemostasis and Thrombosis Unit, Division of Haematology, Haemophilia Clinic, Saint-Luc University Hospital, Brussels, Belgium. Electronic address:
    Joint pain secondary to chronic arthropathy represents one of the most common and debilitating complications of haemophilia, often requiring analgesic care. When compared with nonselective non-steroidal anti-inflammatory drugs (ns-NSAIDs), selective COX-2 inhibitors (coxibs) offer the major advantage of not increasing the bleeding risk, thus being a better choice of analgesics for haemophilia patients. However, several studies have highlighted the cardiovascular risks posed by coxibs and NSAIDs. Read More

    Role of COX-2-derived PGE2 on vascular stiffness and function in hypertension.
    Br J Pharmacol 2016 May 21;173(9):1541-55. Epub 2016 Mar 21.
    Dept. Farmacología, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, Spain.
    Background And Purpose: Prostanoids derived from COX-2 and EP receptors are involved in vascular remodelling in different cardiovascular pathologies. This study evaluates the contribution of COX-2 and EP1 receptors to vascular remodelling and function in hypertension.

    Experimental Approach: Spontaneously hypertensive rats (SHR) and angiotensin II (AngII)-infused (1. Read More

    Prostaglandins from Cytosolic Phospholipase A2α/Cyclooxygenase-1 Pathway and Mitogen-activated Protein Kinases Regulate Gene Expression in Candida albicans-infected Macrophages.
    J Biol Chem 2016 Mar 3;291(13):7070-86. Epub 2016 Feb 3.
    From the Department of Pediatrics, National Jewish Health, Denver, Colorado 80206 and the Departments of Pharmacology and Pathology, University of Colorado Denver, Aurora, Colorado 80045
    In Candida albicans-infected resident peritoneal macrophages, activation of group IVA cytosolic phospholipase A2(cPLA2α) by calcium- and mitogen-activated protein kinases triggers the rapid production of prostaglandins I2 and E2 through cyclooxygenase (COX)-1 and regulates gene expression by increasing cAMP. InC. albicans-infected cPLA2α(-/-)or COX-1(-/-)macrophages, expression ofI l10,Nr4a2, and Ptgs2 was lower, and expression ofTnfα was higher, than in wild type macrophages. Read More

    TNFα up-regulates COX-2 in chronic progressive nephropathy through nuclear accumulation of RelB and NF-κB2.
    Arch Physiol Biochem 2016 24;122(2):88-93. Epub 2016 Feb 24.
    a Department of Nephrology , Nanjing Medical University Affiliated Wuxi Second Hospital , Wuxi , Jiangsu , China.
    Objective: The pathogenesis of progressive nephropathies involves inflammatory factors. The inhibition of cyclooxygenase-2 (COX-2) can limit renal damage and inflammation. However, the mechanism of up-regulation of COX-2 in nephropathy is poorly defined. Read More

    Vitamin D mitigates the adverse effects of obesity on breast cancer in mice.
    Endocr Relat Cancer 2016 Apr 27;23(4):251-64. Epub 2016 Jan 27.
    Department of Medicine-EndocrinologyStanford University School of Medicine, Stanford, CA, USA Stanford Cancer InstituteStanford University School of Medicine, Stanford, CA, USA
    Obesity is an established risk factor for postmenopausal breast cancer (BCa), insulin resistance, and vitamin D deficiency, and all contribute to increased synthesis of mammary estrogens, the drivers of estrogen receptor-positive (ER+) BCa growth. As both dietary vitamin D and calcitriol treatments inhibit breast estrogen synthesis and signaling, we hypothesized that vitamin D would be especially beneficial in mitigating the adverse effects of obesity on ER+BCa. To assess whether obesity exerted adverse effects on BCa growth and whether vitamin D compounds could reduce these unfavorable effects, we employed a diet-induced obesity (DIO) model in ovariectomized C57BL/6 mice. Read More

    Alterations in oxidative, inflammatory and apoptotic events in short-lived and long-lived mice testes.
    Aging (Albany NY) 2016 Jan;8(1):95-110
    Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2 Ciudad de Buenos Aires, Argentina.
    Aged testes undergo profound histological and morphological alterations leading to a reduced functionality. Here, we investigated whether variations in longevity affect the development of local inflammatory processes, the oxidative state and the occurrence of apoptotic events in the testis. To this aim, well-established mouse models with delayed (growth hormone releasing hormone-knockout and Ames dwarf mice) or accelerated (growth hormone-transgenic mice) aging were used. Read More

    Loss of Fatty Acid Binding Protein 4/aP2 Reduces Macrophage Inflammation Through Activation of SIRT3.
    Mol Endocrinol 2016 Mar 20;30(3):325-34. Epub 2016 Jan 20.
    Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455.
    Activation of proinflammatory macrophages plays an important role in the pathogenesis of insulin resistance, type 2 diabetes, and atherosclerosis. Previous work using high fat-fed mice has shown that ablation of the adipocyte fatty acid binding protein (FABP4/aP2) in macrophages leads to an antiinflammatory state both in situ and in vivo, and the mechanism is linked, in part, to increased intracellular monounsaturated fatty acids and the up-regulation of uncoupling protein 2. Here, we show that loss of FABP4/aP2 in macrophages additionally induces sirtuin 3 (SIRT3) expression and that monounsaturated fatty acids (C16:1, C18:1) lead to increased SIRT3 protein expression. Read More

    Epigenetic regulation of cyclooxygenase-2 by methylation of c8orf4 in pulmonary fibrosis.
    Clin Sci (Lond) 2016 Apr 7;130(8):575-86. Epub 2016 Jan 7.
    UCL Respiratory Centre for Inflammation and Tissue Repair, Rayne Building, University College London, London, WC1E 6JF, U.K.
    Fibroblasts derived from the lungs of patients with idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc) produce low levels of prostaglandin (PG) E2, due to a limited capacity to up-regulate cyclooxygenase-2 (COX-2). This deficiency contributes functionally to the fibroproliferative state, however the mechanisms responsible are incompletely understood. In the present study, we examined whether the reduced level of COX-2 mRNA expression observed in fibrotic lung fibroblasts is regulated epigenetically. Read More

    The Role of Indoleamine 2,3-Dioxygenase in Diethylnitrosamine-Induced Liver Carcinogenesis.
    PLoS One 2016 4;11(1):e0146279. Epub 2016 Jan 4.
    First Departments of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
    Indoleamine 2,3-dioxygenase (IDO), a tryptophan-catabolizing intracellular enzyme of the L-kynurenine pathway, causes preneoplastic cells and tumor cells to escape the immune system by inducing immune tolerance; this mechanism might be associated with the development and progression of human malignancies. In the present study, we investigated the role of IDO in diethylnitrosamine (DEN)-induced hepatocarcinogenesis by using IDO-knockout (KO) mice. To induce hepatocellular carcinoma (HCC), hepatic adenoma, and preneoplastic hepatocellular lesions termed foci of cellular alteration (FCA), male IDO-wild-type (WT) and IDO-KO mice with a C57BL/6J background received a single intraperitoneal injection of DEN at 2 weeks of age. Read More

    Effects of rosmarinic acid on cognitive and biochemical alterations in ovariectomized rats treated with D-galactose.
    Folia Histochem Cytobiol 2015 30;53(4):283-93. Epub 2015 Dec 30.
    Department of Biophysics, Akdeniz University, Faculty of Medicine, Arapsuyu, Antalya.
    Introduction: Animal models designed to mimic certain features of Alzheimer's disease (AD) can help us to increase our understanding of the underlying mechanisms of disease. Previous studies have revealed that long-term D-galactose injection combined with ovariectomy results in pathophysiologic alterations associated with AD. Thus, the aim of the present study was to investigate the effects of rosmarinic acid (RA) administration on pathological changes associated with ovariectomy and D-galactose injection, which serve as a two-insult model for AD. Read More

    The exome sequencing identified the mutation in YARS2 encoding the mitochondrial tyrosyl-tRNA synthetase as a nuclear modifier for the phenotypic manifestation of Leber's hereditary optic neuropathy-associated mitochondrial DNA mutation.
    Hum Mol Genet 2016 Feb 8;25(3):584-96. Epub 2015 Dec 8.
    Institute of Genetics, Zhejiang University, School of Medicine, Hangzhou, Zhejiang, China, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China,
    Leber's hereditary optic neuropathy (LHON) is the most common mitochondrial disorder. Nuclear modifier genes are proposed to modify the phenotypic expression of LHON-associated mitochondrial DNA (mtDNA) mutations. By using an exome sequencing approach, we identified a LHON susceptibility allele (c. Read More

    Leucine-rich repeat kinase 2 positively regulates inflammation and down-regulates NF-κB p50 signaling in cultured microglia cells.
    J Neuroinflammation 2015 Dec 9;12:230. Epub 2015 Dec 9.
    Department of Biology, University of Padova, via Ugo Bassi 58/B, 35131, Padova, Italy.
    Background: Over-activated microglia and chronic neuroinflammation contribute to dopaminergic neuron degeneration and progression of Parkinson's disease (PD). Leucine-rich repeat kinase 2 (LRRK2), a kinase mutated in autosomal dominantly inherited and sporadic PD cases, is highly expressed in immune cells, in which it regulates inflammation through a yet unclear mechanism.

    Methods: Here, using pharmacological inhibition and cultured Lrrk2 (-/-) primary microglia cells, we validated LRRK2 as a positive modulator of inflammation and we investigated its specific function in microglia cells. Read More

    Gx-50 reduces β-amyloid-induced TNF-α, IL-1β, NO, and PGE2 expression and inhibits NF-κB signaling in a mouse model of Alzheimer's disease.
    Eur J Immunol 2016 Mar 21;46(3):665-76. Epub 2016 Jan 21.
    School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
    Chronic inflammation, which is regulated by overactivated microglia in the brain, accelerates the occurrence and development of Alzheimer's disease (AD). Gx-50 has been investigated as a novel drug for the treatment of AD in our previous studies. Here, we investigated whether gx-50 possesses anti-inflammatory effects in primary rat microglia and a mouse model of AD, amyloid precursor protein (APP) Tg mice. Read More

    Mulberry fruit prevents LPS-induced NF-κB/pERK/MAPK signals in macrophages and suppresses acute colitis and colorectal tumorigenesis in mice.
    Sci Rep 2015 Nov 30;5:17348. Epub 2015 Nov 30.
    Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.
    Here, we investigated the impact of mulberry fruit (MBF) extracts on lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages, and the therapeutic efficacy of MBF diet in mice with dextran sulfate sodium (DSS)-induced acute colitis and MUC2(-/-) mice with colorectal cancer. In vitro, LPS-induced nitric oxide (NO) production was significantly inhibited by MBF extracts via suppressing the expression of proinflammatory molecules, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-β) and IL-6. Read More

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