1,370 results match your criteria Cyclooxygenase Deficiency


[Vitamin and antioxidant properties of tocopherols: characteristic of the molecular mechanisms of action].

Vopr Pitan 2018 11;87(3):5-11. Epub 2018 May 11.

Federal Research Centre of Nutrition, Biotechnology and Food Safety, Moscow.

The molecular docking method was used to study the structural characteristics determining the competitive transport in the blood, and also the subsequent binding with enzymes of tocopherols and their metabolites to yield a specific biological activity. The target proteins were α-tocopherol-transport protein (α-TTP), tocopherol-associated protein 1 (TAP1), cyclooxygenase-2 (COX-2), protein phosphatase 2A (PP2A) and 3-hydroxy- 3-methylglutaryl-Coenzyme A (HMG-CoA) reductase. RRR-tocopherol (α-, β-, γ- and δ-forms), RRR-13'-carboxychromanol (α-, β-, γ- and δ-forms) and carboxyethyl hydroxychromanol (α-, β-, γ- and δ-forms) were used as ligands in this research. Read More

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http://dx.doi.org/10.24411/0042-8833-2018-10025DOI Listing

Endothelial prostacyclin protects the kidney from ischemia-reperfusion injury.

Pflugers Arch 2018 Nov 9. Epub 2018 Nov 9.

Division of Nephrology, Huashan Hospital, Fudan University, 12 Wulumuqi Road (middle), Shanghai, 200040, China.

Prostacyclin, or PGI, is a product of PGI synthase (PGIS), down-stream of cyclooxygenase pathway. PGI has been demonstrated to play an important role in maintaining renal blood flow. Non-steroidal anti-inflammatory drugs (NSAIDs) that inhibit cyclooxygenase are reported to increase the susceptibility of patients to acute kidney injury (AKI). Read More

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http://link.springer.com/10.1007/s00424-018-2229-6
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http://dx.doi.org/10.1007/s00424-018-2229-6DOI Listing
November 2018
6 Reads

Vitamin D stimulates multiple microRNAs to inhibit CRH and other pro-labor genes in human placenta.

Endocr Connect 2018 Nov 1. Epub 2018 Nov 1.

T Rosen, New Brunswick, United States.

Maternal vitamin D-deficiency is linked to adverse pregnancy outcomes including spontaneous preterm birth (SPB). Placental corticotropin-releasing hormone (CRH) has been proposed to be part of a clock that governs the length of gestation in humans, with elevated maternal serum levels predicting early delivery. In this study we test the hypothesis that vitamin D could contribute to the prevention of preterm labor by inhibiting CRH and other pro-labor mediators. Read More

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https://ec.bioscientifica.com/view/journals/ec/aop/ec-18-034
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http://dx.doi.org/10.1530/EC-18-0345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280586PMC
November 2018
19 Reads

The effect of CA1 administration of orexin-A on hippocampal expression of COX-2 and BDNF in a rat model of orofacial pain.

Arq Neuropsiquiatr 2018 Sep;76(9):603-608

Kerman University of Medical Sciences, Institute of Neuropharmacology, Neuroscience Research Center, Laboratory of Molecular Neuroscience, Kerman, Iran.

Objective: The neuropeptide orexin-A and its receptors are widely distributed in both hippocampal circuitry and pain transmission pathways. Involvement of the CA1 orexin 1 receptor (OX1R) on the modulation of orofacial pain and pain-induced changes in hippocampal expression of cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) was investigated.

Methods: Orofacial pain was induced by an intra-lip injection of capsaicin (100 μg). Read More

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http://www.scielo.br/scielo.php?script=sci_arttext&pid=S
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http://dx.doi.org/10.1590/0004-282X20180099DOI Listing
September 2018
5 Reads

Genetic variant in the 3'-untranslated region of the COX2 gene is associated with type 2 diabetes: A hospital-based case-control study.

Prostaglandins Leukot Essent Fatty Acids 2018 Oct 26;137:39-42. Epub 2018 Jul 26.

Department of Medical Biology, Medical Faculty, Eskisehir Osmangazi University, Eskisehir, Turkey. Electronic address:

Type 2 diabetes (T2DM) is caused by the decreased β-cell mass and insulin deficiency, and disease is characterized by hypoglycemia. The insulin resistance also plays an important role in T2DM pathogenesis. Insulin resistance is the reduced biological response to insulin at the normal concentration in the circulation and develops with the influence of environmental factors with genetic abnormalities. Read More

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http://dx.doi.org/10.1016/j.plefa.2018.07.012DOI Listing
October 2018
2 Reads

The Dynamic Changes of Gut Microbiota in Deficient Mice.

Int J Mol Sci 2018 Sep 18;19(9). Epub 2018 Sep 18.

College of Basic Medicine, Xinxiang Medical University, Xinxiang 453003, Henan, China.

Gut dysbiosis is associated with colitis-associated colorectal carcinogenesis, and the genetic deficiency of the gene causes spontaneous development of colitis and colorectal cancer. Whether there are changes of gut microbiota and a linkage between the changes of microbiota and intestinal pathology in mice are unclear. and mice were generated by backcrossing from mice, and the fecal samples were collected at different dates (48th, 98th, 118th, 138th, and 178th day). Read More

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http://dx.doi.org/10.3390/ijms19092809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164417PMC
September 2018

Analysis of gene expression and functional changes of adrenal gland in a rat model of kidney yang deficiency syndrome treated with decoction.

Exp Ther Med 2018 Oct 25;16(4):3107-3115. Epub 2018 Jul 25.

Department of Hepatology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi 530023, P.R. China.

decoction (SND), a well-known traditional Chinese medicine, has been used to treat kidney deficiency for ~1,800 years. The present study aimed to evaluate the effects of SND treatment on hypothalamic-pituitary-adrenal axis hormones in a rat model of deficiency and to explore the molecular mechanisms using microarray analysis of adrenal glands and adrenocortical cell culture systems. The results indicated that SND treatment recovered circulating serum cortisol, adrenocortical hormone (ACTH) and testosterone levels in a y deficiency model. Read More

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http://dx.doi.org/10.3892/etm.2018.6521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125868PMC
October 2018

Endothelial SIRT1 prevents age-induced impairment of vasodilator responses by enhancing the expression and activity of soluble guanylyl cyclase in smooth muscle cells.

Cardiovasc Res 2018 Aug 27. Epub 2018 Aug 27.

State Key Laboratory of Pharmaceutical Biotechnology and Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, China.

Rationale: Aged arteries are characterized by attenuated vasodilator and enhanced vasoconstrictor responses, which contribute to the development of diseases such as arterial hypertension, atherosclerosis and heart failure. SIRT1 is a longevity regulator exerting protective functions against vascular ageing, although the underlying mechanisms remain largely unknown.

Objective: The present study was designed to elucidate the signaling pathways involved in endothelial SIRT1-mediated vasodilator responses in the arteries of young and old mice. Read More

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https://academic.oup.com/cardiovascres/advance-article/doi/1
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http://dx.doi.org/10.1093/cvr/cvy212DOI Listing
August 2018
9 Reads
5.940 Impact Factor

[Expression of COX-1 and COX-2 in the Platelet of Iron Deficiency Anemia Women at Childbearing Age and Its Clinical Significance].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2018 Aug;26(4):1162-1166

Department of Laboratorial Examination,Wujin people's hospital, Changzhou, 213017 Jiangsu Province, China. E-mail:

Objective: To detect the expression level of cyclooxygenase-1(COX-1) and cyclooxygenase-2(COX-2) in the platelet of iron deficiency anemia(IDA)women at childbearing age and to explore its correlation with the different indexes of anemia and platelets.

Methods: Forty female IDA patients at childbearing age and 35 healthy controls were enrolled in this study. The Flow cytometry was used to detect the expression of platelet COX-1 and COX-2,the platelet aggregation function as examined by turbidimetric method,and the levels of serum ferritin were analyzed by electrochemical luminescence method,the leval of serum iron was determined by ELISA,and the correlation of different indexes was analyzed. Read More

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http://dx.doi.org/10.7534/j.issn.1009-2137.2018.04.036DOI Listing
August 2018
2 Reads

The pro-oxidant adaptor p66SHC promotes B cell mitophagy by disrupting mitochondrial integrity and recruiting LC3-II.

Autophagy 2018 6;14(12):2117-2138. Epub 2018 Sep 6.

a Department of Life Sciences , University of Siena , Siena , Italy.

Macroautophagy/autophagy has emerged as a central process in lymphocyte homeostasis, activation and differentiation. Based on our finding that the p66 isoform of SHC1 (p66SHC) pro-apoptotic ROS-elevating SHC family adaptor inhibits MTOR signaling in these cells, here we investigated the role of p66SHC in B-cell autophagy. We show that p66SHC disrupts mitochondrial function through its CYCS (cytochrome c, somatic) binding domain, thereby impairing ATP production, which results in AMPK activation and enhanced autophagic flux. Read More

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http://dx.doi.org/10.1080/15548627.2018.1505153DOI Listing
September 2018
2 Reads

Effects of low-magnitude high-frequency vibration on osteoblasts are dependent on estrogen receptor α signaling and cytoskeletal remodeling.

Biochem Biophys Res Commun 2018 09 7;503(4):2678-2684. Epub 2018 Aug 7.

Institute of Orthopaedic Research and Biomechanics, Ulm University, Germany.

Clinical and experimental studies demonstrate the potential of low-magnitude high-frequency vibration (LMHFV) to enhance bone formation in the intact skeleton and during fracture healing. Moreover, it was shown that the effects of vibration therapy during fracture healing are highly dependent on the estrogen status of the vibrated individual and that estrogen receptor (ER) α signaling plays a major role in mechanotransduction of LMHFV. Because it is known that LMHFV can directly act on osteogenic cells, we hypothesize that the differential effects of LMHFV in the presence and absence of estrogen are mediated by ERα signaling in osteoblasts. Read More

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http://dx.doi.org/10.1016/j.bbrc.2018.08.023DOI Listing
September 2018

Colonic epithelial mTORC1 promotes ulcerative colitis through COX-2-mediated Th17 responses.

Mucosal Immunol 2018 11 6;11(6):1663-1673. Epub 2018 Aug 6.

Department of Cell Biology, School of Basic Medical Science, Southern Medical University, 510515, Guangzhou, China.

The functional role of colonic epithelium in the pathogenesis of ulcerative colitis (UC) remains unclear. Here, we reveal a novel mechanism by which colonic epithelia recruit T helper-17 (Th17) cells during the onset of UC. mTOR complex 1 (mTORC1) was hyper-activated in colonic epithelia of UC mice. Read More

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http://dx.doi.org/10.1038/s41385-018-0018-3DOI Listing
November 2018
9 Reads
7.374 Impact Factor

Cold-Induced Browning of Inguinal White Adipose Tissue Is Independent of Adipose Tissue Cyclooxygenase-2.

Cell Rep 2018 Jul;24(4):809-814

Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-5127, USA. Electronic address:

Previous studies using genetic mouse models have implicated COX-2 in the browning of white adipose tissues (WATs) in mice during cold exposure. However, COX-2 is important during development, and conventional knockouts (KOs) exhibit many defects, conditioned by genetic background. Similarly, the physiological relevance of transgenic overexpression of COX-2 is questionable. Read More

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http://dx.doi.org/10.1016/j.celrep.2018.06.082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6118132PMC
July 2018
2 Reads

Impaired post-irradiation survival of cyclooxygenase-2-deficient mice.

Physiol Res 2018 Nov 25;67(5):809-812. Epub 2018 Jul 25.

Department of Cell Biology and Radiobiology, Institute of Biophysics of the Czech Academy of Sciences, Brno, Czech Republic.

We investigated and evaluated post-irradiation survival in cyclooxygenase-2-deficient (COX-2 KO) mice. Thirty-day survival following exposure of COX-2 KO mice to a lethal dose of 8.5 Gy of gamma-rays was observed to be statistically significantly lower in both males and females, as well as when the sexes were merged, in comparisons with their wild-type counterparts. Read More

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November 2018

HDAC9 promotes brain ischemic injury by provoking IκBα/NF-κB and MAPKs signaling pathways.

Biochem Biophys Res Commun 2018 Sep 18;503(3):1322-1329. Epub 2018 Jul 18.

Department of Anesthesiology, China Japan Union Hospital of Jilin University, Jilin, 130033, China. Electronic address:

Ischemic stroke is an acute cerebrovascular disease due to poor blood flow to the brain. Nevertheless, there is still no effective therapy for it and the pathology contributing to ischemic stroke is not fully understood. Histone Deacetylase 9 (HDAC9) is a class IIa chromatin-modifying enzyme. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S0006291X183153
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http://dx.doi.org/10.1016/j.bbrc.2018.07.043DOI Listing
September 2018
2 Reads

JNK2 silencing and caspase-9 activation by hyperosmotic polymer inhibits tumor progression.

Int J Biol Macromol 2018 Dec 10;120(Pt B):2215-2224. Epub 2018 Jul 10.

Department of Biosystems & Biomaterials Science and Engineering, Seoul National University, Seoul 151-921, Republic of Korea; Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea. Electronic address:

c-Jun N-terminal kinase 2 (JNK2) is primarily responsible for the oncogenic transformation of the transcription factor c-Jun. Expression of the proto-oncogene c-Jun progresses the cell cycle from G1 to S phase, but when its expression becomes awry it leads to uncontrolled proliferation and angiogenesis. Delivering a JNK2 siRNA (siJNK2) in tumor tissue was anticipated to reverse the condition with subsequent onset of apoptosis which predominantly requires an efficient delivering system capable of penetrating through the compact tumor mass. Read More

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http://dx.doi.org/10.1016/j.ijbiomac.2018.07.019DOI Listing
December 2018
10 Reads

Therapeutic potential of dinitrobenzene sulfonic acid (DNBS)-induced colitis in mice by targeting IL-1β and IL-18.

Biochem Pharmacol 2018 Sep 28;155:150-161. Epub 2018 Jun 28.

Department of Chemical Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres 31, 98166 Messina, Italy; Manchester Biomedical Research Centre, Manchester Royal Infirmary, School of Medicine, University of Manchester, Manchester, United Kingdom. Electronic address:

Interleukin (IL)-1 and IL-18 belong to the IL-1 family of ligands, and their receptors are members of the IL-1 receptor family. Both cytokines drive an extensive range of pro-inflammatory networks in many cell types using common signal transduction cascades. Anyway, differences in signaling pathways exist. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00062952183025
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http://dx.doi.org/10.1016/j.bcp.2018.06.029DOI Listing
September 2018
15 Reads

Dimethylthiourea ameliorates carbon tetrachloride-induced acute liver injury in ovariectomized mice.

Biomed Pharmacother 2018 Aug 25;104:427-436. Epub 2018 May 25.

Lab. Forensic Toxicol., Fac. Pharmacy, Takasaki Univ. Health and Welfare, 60 Nakaorui-machi, Takasaki 370-0033, Japan.

Aims: In order to clarify hepato-protective actions of estrogen, we examined the progress of carbon tetrachloride (CCl)-induced acute liver injury (ALI) in sham and ovariectomized (ovx) mice and the effects of dimethylthiourea (DMTU), a hydroxyl radical scavenger, and meloxicam (Melo), a selective cox-2 inhibitor, on the development of CCl-induced ALI.

Main Methods: Female C57BL/6 J mice weighing 15-20 g were performed sham or ovx operation at 8 weeks of age. Blood and liver samples were collected 15 and 24 h after CCl administration. Read More

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http://dx.doi.org/10.1016/j.biopha.2018.05.065DOI Listing
August 2018
1 Read

Ambient particulate matter activates the aryl hydrocarbon receptor in dendritic cells and enhances Th17 polarization.

Toxicol Lett 2018 Aug 22;292:85-96. Epub 2018 Apr 22.

Center for Health and the Environment, University of California, Davis, 95616, USA; Department of Environmental Toxicology, University of California, Davis, 95616, USA. Electronic address:

The objective of this study was to explore the role of the aryl hydrocarbon receptor (AhR) in ambient particulate matter (PM)-mediated activation of dendritic cells (DCs) and Th17-immune responses in vitro. To assess the potential role of the AhR in PM-mediated activation of DCs, co-stimulation, and cytokine expression, bone marrow (BM)-derived macrophages and DCs from C57BL/6 wildtype or AhR knockout (AhR) mice were treated with PM. Th17 differentiation was assessed via co-cultures of wildtype or AhR BMDCs with autologous naive T cells. Read More

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http://dx.doi.org/10.1016/j.toxlet.2018.04.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5971007PMC
August 2018
4 Reads

Hypothermic preconditioning but not ketamine reduces oxygen and glucose deprivation induced neuronal injury correlated with downregulation of COX-2 expression in mouse hippocampal slices.

J Pharmacol Sci 2018 May 7;137(1):30-37. Epub 2018 Apr 7.

Department of Anesthesiology, The First People's Hospital of Lianyungang, Lianyungang, China. Electronic address:

Hypothermic preconditioning is an effective treatment for limiting ischemic injury, but the mechanism is poorly understood. This study was aimed to explore the effect of hypothermic and ketamine preconditioning on oxygen and glucose deprivation (OGD) induced neuronal injury in mouse hippocampal slices, and to investigate its possible mechanism. The population spike (PS) was recorded in the CA1 region of mouse hippocampal slices using extracellular recordings, Na/K ATPase activity in slices was determined by spectrophotometer and the expression of Cyclooxygenase-2 (COX-2) was measured by Western blot. Read More

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http://dx.doi.org/10.1016/j.jphs.2018.04.001DOI Listing

Neuronal SphK1 acetylates COX2 and contributes to pathogenesis in a model of Alzheimer's Disease.

Nat Commun 2018 04 16;9(1):1479. Epub 2018 Apr 16.

Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, 41566, South Korea.

Although many reports have revealed the importance of defective microglia-mediated amyloid β phagocytosis in Alzheimer's disease (AD), the underlying mechanism remains to be explored. Here we demonstrate that neurons in the brains of patients with AD and AD mice show reduction of sphingosine kinase1 (SphK1), leading to defective microglial phagocytosis and dysfunction of inflammation resolution due to decreased secretion of specialized proresolving mediators (SPMs). Elevation of SphK1 increased SPMs secretion, especially 15-R-Lipoxin A4, by promoting acetylation of serine residue 565 (S565) of cyclooxygenase2 (COX2) using acetyl-CoA, resulting in improvement of AD-like pathology in APP/PS1 mice. Read More

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http://dx.doi.org/10.1038/s41467-018-03674-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902554PMC
April 2018
21 Reads
2 Citations
10.742 Impact Factor

Cyclooxygenase-2 deficiency causes delayed ossification of lumbar vertebral endplates.

Am J Transl Res 2018 15;10(3):718-730. Epub 2018 Mar 15.

Department of Biochemistry, Rush University Medical CenterChicago, USA.

Based on previous findings that cyclooxygenase-2 (COX-2) is a critical molecule in chondrocyte differentiation and skeletal repair, we hypothesized that COX-2 deficiency or inhibition affects the ossification of vertebral endplates (VEP) and degeneration of intervertebral discs (IVD) and thus is involved in the pathogenesis of low back pain (LBP). We aimed to delineate the COX-2 working mechanism and its interacting molecules, and to explore the effect of NSAIDs and selective COX-2 inhibitor on degenerative spinal diseases. Here, lumbar spinal samples harvested from Cox-2 mutant () and wild type (WT) mice were used for histological examinations. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5883113PMC

Knockdown delta-5-desaturase in breast cancer cells that overexpress COX-2 results in inhibition of growth, migration and invasion via a dihomo-γ-linolenic acid peroxidation dependent mechanism.

BMC Cancer 2018 03 27;18(1):330. Epub 2018 Mar 27.

Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, 58108, USA.

Background: Cyclooxygenase-2 (COX-2), the inducible COX form, is a bi-functional membrane-bound enzyme that typically metabolizes arachidonic acid (downstream ω-6 fatty acid) to form 2-series of prostaglandins known to be involved in cancer development. Overexpression of COX-2 has been found in a majority of breast carcinomas, and has also been associated with increased severity and the development of the metastasis. Our lab recently demonstrated that COX-2 can also metabolize dihomo-γ-linolenic acid (DGLA, a precursor of ω-6 arachidonic acid) to produce an anti-cancer byproduct, 8-hydroxyoctanoic acid (8-HOA) that can inhibit growth and migration of colon and pancreatic cancer cells. Read More

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http://dx.doi.org/10.1186/s12885-018-4250-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870477PMC
March 2018
30 Reads
1 Citation
3.360 Impact Factor

Ablation of the leptin receptor in myeloid cells impairs pulmonary clearance of Streptococcus pneumoniae and alveolar macrophage bactericidal function.

Am J Physiol Lung Cell Mol Physiol 2018 Jul 22;315(1):L78-L86. Epub 2018 Mar 22.

Department of Integrative and Molecular Physiology, University of Michigan , Ann Arbor, Michigan.

Leptin is a pleiotropic hormone produced by white adipose tissue that regulates appetite and many physiological functions, including the immune response to infection. Genetic leptin deficiency in humans and mice impairs host defenses against respiratory tract infections. Since leptin deficiency is associated with obesity and other metabolic abnormalities, we generated mice that lack the leptin receptor (LepRb) in cells of the myeloid linage (LysM-LepRb-KO) to evaluate its impact in lean metabolically normal mice in a murine model of pneumococcal pneumonia. Read More

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http://dx.doi.org/10.1152/ajplung.00447.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087898PMC
July 2018
6 Reads

Dominant Role for Regulatory T Cells in Protecting Females Against Pulmonary Hypertension.

Circ Res 2018 Jun 15;122(12):1689-1702. Epub 2018 Mar 15.

From the Stanford University School of Medicine, Department of Medicine, CA (R.T., P.M., T.S., J.Q., M.S., L.P.N., A.L., M.R., A.H., L.A., M.R.N.)

Rationale: Pulmonary arterial hypertension (PH) is a life-threatening condition associated with immune dysregulation and abnormal regulatory T cell (Treg) activity, but it is currently unknown whether and how abnormal Treg function differentially affects males and females.

Objective: To evaluate whether and how Treg deficiency differentially affects male and female rats in experimental PH.

Methods And Results: Male and female athymic rats, lacking Tregs, were treated with the VEGFR2 (vascular endothelial growth factor receptor 2) inhibitor SU5416 or chronic hypoxia and evaluated for PH; some animals underwent Treg immune reconstitution before SU5416 administration. Read More

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http://dx.doi.org/10.1161/CIRCRESAHA.117.312058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993601PMC
June 2018
4 Reads

Celecoxib Ameliorates Seizure Susceptibility in Autosomal Dominant Lateral Temporal Epilepsy.

J Neurosci 2018 Mar 28;38(13):3346-3357. Epub 2018 Feb 28.

Department of Neurobiology, Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China,

Autosomal dominant lateral temporal epilepsy (ADLTE) is an inherited syndrome caused by mutations in the leucine-rich glioma inactivated 1 (LGI1) gene. It is known that glutamatergic transmission is altered in LGI1 mutant mice, and seizures can be reduced by restoring LGI1 function. Yet, the mechanism underlying ADLTE is unclear. Read More

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http://dx.doi.org/10.1523/JNEUROSCI.3245-17.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884462PMC
March 2018
34 Reads
1 Citation
6.340 Impact Factor

Teriparatide (human PTH) compensates for impaired fracture healing in COX-2 deficient mice.

Bone 2018 05 3;110:150-159. Epub 2018 Feb 3.

Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, USA. Electronic address:

Genetic ablation of cyclooxygenase-2 (COX-2) in mice is known to impair fracture healing. To determine if teriparatide (human PTH) can promote healing of Cox-2-deficient fractures, we performed detailed in vivo analyses using a murine stabilized tibia fracture model. Periosteal progenitor cell proliferation as well as bony callus formation was markedly reduced in Cox-2 mice at day 10 post-fracture. Read More

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http://dx.doi.org/10.1016/j.bone.2018.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878736PMC
May 2018
3 Reads

Functional loss of p53 cooperates with the in vivo microenvironment to promote malignant progression of gastric cancers.

Sci Rep 2018 02 2;8(1):2291. Epub 2018 Feb 2.

Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan.

p53 mutations are frequently detected in malignant gastric cancers. However, the molecular mechanisms by which loss of p53 function promotes gastric cancer are not clear. We utilized Gan mice (K19-Wnt1/C2mE), which have functional p53 and develop intestinal-type gastric tumors, to investigate the role of p53 in gastric cancer progression by knocking out p53. Read More

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http://dx.doi.org/10.1038/s41598-018-20572-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797237PMC
February 2018

Epigenetic modification of Nrf2 by sulforaphane increases the antioxidative and anti-inflammatory capacity in a cellular model of Alzheimer's disease.

Eur J Pharmacol 2018 Apr 31;824:1-10. Epub 2018 Jan 31.

Department of Neurology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan, China. Electronic address:

Sulforaphane was reported to exert neuroprotective effects via upregulating expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and has received increasing attention as an alternative candidate for treatment of Alzheimer's disease (AD). However, the mechanism to account for Nrf2 upregulation by sulforaphane in AD remains unknown. Herein, we found that sulforaphane upregulated Nrf2 expression and promoted Nrf2 nuclear translocation via decreasing DNA methylation levels of the Nrf2 promoter in mouse neuroblastoma N2a cells stably expressing human Swedish mutant amyloid precursor protein (N2a/APPswe cells), a cellular model of AD. Read More

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http://dx.doi.org/10.1016/j.ejphar.2018.01.046DOI Listing
April 2018
1 Read

Regulator of calcineurin 1 modulates vascular contractility and stiffness through the upregulation of COX-2-derived prostanoids.

Pharmacol Res 2018 Jul 5;133:236-249. Epub 2018 Jan 5.

Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, Spain; CIBER de Enfermedades Cardiovasculares, Spain. Electronic address:

Cyclooxygenase-2 (COX-2) derived-prostanoids participate in the altered vascular function and mechanical properties in cardiovascular diseases. We investigated whether regulator of calcineurin 1 (Rcan1) participates in vascular contractility and stiffness through the regulation of COX-2. For this, wild type (Rcan1) and Rcan1-deficient (Rcan1) mice untreated or treated with the COX-2 inhibitor rofecoxib were used. Read More

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http://dx.doi.org/10.1016/j.phrs.2018.01.001DOI Listing
July 2018
5 Reads

Mechanism of Protein Carbonylation in Glutathione-Depleted Rat Brain Slices.

Neurochem Res 2018 Mar 20;43(3):609-618. Epub 2017 Dec 20.

Department of Cell Biology and Physiology, University of New Mexico - Health Sciences Center, MSC08 4750 1 University of New Mexico, Albuquerque, NM, 87131-0001, USA.

This study was conducted to further our understanding about the link between lipid peroxidation and protein carbonylation in rat brain slices incubated with the glutathione (GSH)-depletor diethyl maleate. Using this in vitro system of oxidative stress, we found that there is a significant lag between the appearance of carbonylated proteins and GSH depletion, which seems to be due to the removal of oxidized species early on in the incubation by the mitochondrial Lon protease. Upon acute GSH depletion, protein carbonyls accumulated mostly in mitochondria and to a lesser degree in other subcellular fractions that also contain high levels of polyunsaturated lipids. Read More

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http://dx.doi.org/10.1007/s11064-017-2456-9DOI Listing

Proteomic Analysis Shows Constitutive Secretion of MIF and p53-associated Activity of COX-2 Lung Fibroblasts.

Genomics Proteomics Bioinformatics 2017 12 13;15(6):339-351. Epub 2017 Dec 13.

Department of Rheumatology, New York University Hospital for Joint Diseases, New York, NY 10003, USA; Departments of Pathology, New York University School of Medicine, New York, NY 10003, USA; Department of Bio-Medical Engineering, Virginia Tech, Blacksburg, VA 24060, USA; RheuMatric Inc., Blacksburg, VA 24061, USA. Electronic address:

The differential expression of two closelyassociated cyclooxygenase isozymes, COX-1 and COX-2, exhibited functions beyond eicosanoid metabolism. We hypothesized that COX-1 or COX-2 knockout lung fibroblasts may display altered protein profiles which may allow us to further differentiate the functional roles of these isozymes at the molecular level. Proteomic analysis shows constitutive production of macrophage migration inhibitory factor (MIF) in lung fibroblasts derived from COX-2 but not wild-type (WT) or COX-1 mice. Read More

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http://dx.doi.org/10.1016/j.gpb.2017.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828655PMC
December 2017
21 Reads

Sildenafil (Viagra®) Prevents Cox-1/ TXA2 Pathway-Mediated Vascular Hypercontractility in ApoE-/- Mice.

Cell Physiol Biochem 2017 7;44(5):1796-1809. Epub 2017 Dec 7.

Laboratory of Translational Physiology, Federal University of Espirito Santo, Vitoria, Brazil.

Background/aims: The atherosclerotic apolipoprotein E-deficient (apoE-/-) mouse exhibits impaired vasodilation and enhanced vasoconstriction responsiveness. The objectives of this study were: a) to determine the relative contribution of cyclooxygenases (Cox-1 and Cox-2), thromboxane A2 (TXA2) and endothelin-1 (ET-1) to enhancing vascular hyperresponsiveness in this model of atherosclerosis and b) to investigate the beneficial effects of the phosphodiesterase 5 inhibitor sildenafil on this endothelial dysfunction.

Methods: Adult male apoE-/- mice were treated with sildenafil (40 mg/kg/day, for 3 weeks) and compared with non-treated ApoE-/- and wild-type mice. Read More

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http://dx.doi.org/10.1159/000485817DOI Listing
March 2018
9 Reads

Effects of shinbuto and ninjinto on prostaglandin E production in lipopolysaccharide-treated human gingival fibroblasts.

PeerJ 2017 1;5:e4120. Epub 2017 Dec 1.

Department of Pharmacology, Matsumoto Dental University, Shiojiri, Nagano, Japan.

Previously, we revealed that several kampo medicines used for patients with excess and/or medium patterns (kakkonto (TJ-1), shosaikoto (TJ-9), hangeshashinto (TJ-14), and orento (TJ-120)) reduced prostaglandin (PG)E levels using LPS-treated human gingival fibroblasts (HGFs). Recently, we examined other kampo medicines used for patients with the deficiency pattern [bakumondoto (TJ-29), shinbuto (TJ-30), ninjinto (TJ-32), and hochuekkito (TJ-41)] and the herbs comprising shinbuto and ninjinto using the same experimental model. Shinbuto and ninjinto concentration-dependently reduced LPS-induced PGE production by HGFs, whereas hochuekkito weakly reduced and bakumondoto did not reduce PGE production. Read More

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http://dx.doi.org/10.7717/peerj.4120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713626PMC
December 2017
1 Read

Bioassay-guided Isolation of Neuroprotective Fatty Acids from against 1-methyl-4-phenylpyridinium-induced Neurotoxicity.

Pharmacogn Mag 2017 Oct-Dec;13(52):627-633. Epub 2017 Nov 13.

Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Objective: Parkinson's disease, a slowly progressive neurological disease, is associated with degeneration of the basal ganglia of the brain and a deficiency of the neurotransmitter dopamine. The main aspects of researches are the protection of normal neurons against degeneration. Fatty acids (FAs), the key structural elements of dietary lipids, are carboxylic straight chains and notable parameters in nutritional and industrial usefulness of a plant. Read More

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http://dx.doi.org/10.4103/pm.pm_470_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701402PMC
November 2017
1 Read

Inhibition of monoacylglycerol lipase terminates diazepam-resistant status epilepticus in mice and its effects are potentiated by a ketogenic diet.

Epilepsia 2018 01 24;59(1):79-91. Epub 2017 Nov 24.

Department of Neuroscience, IRCCS-Mario Negri Institute for Pharmacological Research, Milano, Italy.

Objective: Status epilepticus (SE) is a life-threatening and commonly drug-refractory condition. Novel therapies are needed to rapidly terminate seizures to prevent mortality and morbidity. Monoacylglycerol lipase (MAGL) is the key enzyme responsible for the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG) and a major contributor to the brain pool of arachidonic acid (AA). Read More

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http://dx.doi.org/10.1111/epi.13950DOI Listing
January 2018
15 Reads

Lack of TNF-α signaling through p55 makes the mice more susceptible to acute infection but does not alter state of latency and reactivation of HSV-1.

Virus Res 2018 01 4;244:1-5. Epub 2017 Nov 4.

Institute of Science, Nirma University, Ahmedabad, Gujarat, India; Medical Virology Section, Laboratory of Clinical Investigation, NIAID, NIH, Bethesda, MD, USA. Electronic address:

TNF-α has been shown to play an important role in pathogenesis and latency of HSV-1 infections. TNF-α signals through TNFR1 (p55) and TNFR2 (p75), and signaling through p55 generally results in gene activation leading to induction of inflammatory responses. Here, we studied the role of TNF-α signaling in latent virus reactivation in p55-knock out (KO) mouse model of ocular HSV-1 infection. Read More

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http://dx.doi.org/10.1016/j.virusres.2017.11.004DOI Listing
January 2018
5 Reads

Host-based lipid inflammation drives pathogenesis in infection.

Proc Natl Acad Sci U S A 2017 11 6;114(47):12596-12601. Epub 2017 Nov 6.

Department of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, MD 21201;

Mass spectrometry imaging (MSI) was used to elucidate host lipids involved in the inflammatory signaling pathway generated at the host-pathogen interface during a septic bacterial infection. Using as a model organism, a bacterial lipid virulence factor (endotoxin) was imaged and identified along with host phospholipids involved in the splenic response in murine tissues. Here, we demonstrate detection and distribution of endotoxin in a lethal murine infection model, in addition to determining the temporally and spatially resolved innate lipid inflammatory response in both 2D and 3D renderings using MSI. Read More

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http://dx.doi.org/10.1073/pnas.1712887114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703311PMC
November 2017
4 Reads

Coexpression of NOS2 and COX2 accelerates tumor growth and reduces survival in estrogen receptor-negative breast cancer.

Proc Natl Acad Sci U S A 2017 12 27;114(49):13030-13035. Epub 2017 Oct 27.

Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702;

Proinflammatory signaling pathways are commonly up-regulated in breast cancer. In estrogen receptor-negative (ER) and triple-negative breast cancer (TNBC), nitric oxide synthase-2 (NOS2) and cyclooxygenase-2 (COX2) have been described as independent predictors of disease outcome. We further explore these findings by investigating the impact of their coexpression on breast cancer survival. Read More

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http://dx.doi.org/10.1073/pnas.1709119114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5724261PMC
December 2017
16 Reads

Reactive astrocyte COX2-PGE2 production inhibits oligodendrocyte maturation in neonatal white matter injury.

Glia 2017 12 30;65(12):2024-2037. Epub 2017 Aug 30.

Department of Pediatrics and Division of Neonatology.

Inflammation is a major risk factor for neonatal white matter injury (NWMI), which is associated with later development of cerebral palsy. Although recent studies have demonstrated maturation arrest of oligodendrocyte progenitor cells (OPCs) in NWMI, the identity of inflammatory mediators with direct effects on OPCs has been unclear. Here, we investigated downstream effects of pro-inflammatory IL-1β to induce cyclooxygenase-2 (COX2) and prostaglandin E2 (PGE2) production in white matter. Read More

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http://dx.doi.org/10.1002/glia.23212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5753598PMC
December 2017
25 Reads

Selenium Deficiency Augments the Levels of Inflammatory Factors and Heat Shock Proteins via the Redox Regulatory Pathway in the Skeletal Muscles of Mice.

Biol Trace Elem Res 2018 Apr 5;182(2):309-316. Epub 2017 Aug 5.

Department of Osteology, The Daqing Oilfield General Hospital, Daqing, 163319, Heilongjiang, People's Republic of China.

Dietary selenium (Se) deficiency is known to cause myodynia syndrome and Se influences immune responses by changing the expression of inflammatory cytokines and heat shock proteins (Hsps), but the details are not completely elucidated. In the present study, 72 1-day-old mice were divided into two groups; the first group was fed a Se-sufficient diet, while the second group was fed a Se-deficient diet. Skeletal muscles and blood samples were taken from all mice after 42 days of treatment. Read More

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http://dx.doi.org/10.1007/s12011-017-1100-5DOI Listing
April 2018
6 Reads

Compensatory Vasodilator Mechanisms in the Ophthalmic Artery of Endothelial Nitric Oxide Synthase Gene Knockout Mice.

Sci Rep 2017 Aug 2;7(1):7111. Epub 2017 Aug 2.

Department of Ophthalmology, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany.

Nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) plays an important role in the maintenance of ocular vascular homeostasis. Therefore, perturbations in vascular NO synthesis have been implicated in the pathogenesis of several ocular diseases. We recently reported that eNOS contributes significantly to vasodilation of the mouse ophthalmic artery. Read More

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http://dx.doi.org/10.1038/s41598-017-07768-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541003PMC
August 2017
16 Reads

Is Aortic Aneurysm Preventable?

Authors:
Undurti N Das

J Transl Int Med 2017 Jun 30;5(2):72-78. Epub 2017 Jun 30.

UND Life Sciences, 2221, NW 5th St, Battle Ground, WA 98604, USA.

Abdominal aortic aneurysm (AAA) is a chronic inflammatory condition, triggered by the local accumulation of macrophages, oxidative stress and damage to the aortic wall. Pro-inflammatory eicosanoids seem to play a significant role in AAA. The pro-inflammatory events seen in AAA could be due to a deficiency of anti-inflammatory eicosanoids such as lipoxin A4 (LXA4), resolvins, protectins and maresins as a result of reduced tissue concentrations of their precursors: arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Read More

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http://dx.doi.org/10.1515/jtim-2017-0022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506405PMC
June 2017
4 Reads

Tuberin Regulates Prostaglandin Receptor-Mediated Viability, via Rheb, in mTORC1-Hyperactive Cells.

Mol Cancer Res 2017 10 14;15(10):1318-1330. Epub 2017 Jul 14.

Department of Internal Medicine, Pulmonary, Critical Care and Sleep Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.

Tuberous sclerosis complex (TSC) is a tumor-suppressor syndrome affecting multiple organs, including the brain, skin, kidneys, heart, and lungs. TSC is associated with mutations in or resulting in hyperactivation of mTOR complex 1 (mTORC1). Clinical trials demonstrate that mTORC1 inhibitors decrease tumor volume and stabilize lung function in TSC patients; however, mTOR inhibitors are cytostatic not cytocidal, and long-term benefits and toxicities are uncertain. Read More

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http://dx.doi.org/10.1158/1541-7786.MCR-17-0077DOI Listing
October 2017
18 Reads

MDR1A deficiency restrains tumor growth in murine colitis-associated carcinogenesis.

PLoS One 2017 7;12(7):e0180834. Epub 2017 Jul 7.

Experimental Gastroenterology, Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany.

Patients with Ulcerative Colitis (UC) have an increased risk to develop colitis-associated colorectal cancer (CAC). Here, we found that protein expression of ABCB1 (ATP Binding Cassette Subfamily B Member 1) / MDR1 (multidrug resistance 1) was diminished in the intestinal mucosa of patients with active UC with or without CAC, but not in non-UC patients with sporadic colon cancer. We investigated the consequences of ABCB1/MDR1 loss-of-function in a common murine model for CAC (AOM/DSS). Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0180834PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501609PMC
September 2017
14 Reads

Autotaxin-lysophosphatidic acid-LPA signaling at the embryo-epithelial boundary controls decidualization pathways.

EMBO J 2017 07 6;36(14):2146-2160. Epub 2017 Jun 6.

Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan

During pregnancy, up-regulation of heparin-binding (HB-) EGF and cyclooxygenase-2 (COX-2) in the uterine epithelium contributes to decidualization, a series of uterine morphological changes required for placental formation and fetal development. Here, we report a key role for the lipid mediator lysophosphatidic acid (LPA) in decidualization, acting through its G-protein-coupled receptor LPA in the uterine epithelium. Knockout of or inhibition of the LPA-producing enzyme autotaxin (ATX) in pregnant mice leads to HB-EGF and COX-2 down-regulation near embryos and attenuates decidual reactions. Read More

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http://emboj.embopress.org/lookup/doi/10.15252/embj.20169629
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http://dx.doi.org/10.15252/embj.201696290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509998PMC
July 2017
47 Reads

Prostaglandin-endoperoxide synthase-2 deletion affects the natural trafficking of Annexin A2 in monocytes and favours venous thrombosis in mice.

Thromb Haemost 2017 07 24;117(8):1486-1497. Epub 2017 May 24.

Silvia S. Barbieri, PhD, Centro Cardiologico Monzino, IRCCS, Via Parea 4, 20138 Milano, Italy, Tel.: +39 02 50318357, Fax: +39 02 50318250, E-mail:

Deep-vein thrombosis (DVT) is a common condition that often leads to pulmonary thromboembolism (VTE) and death. The role of prostaglandin-endoperoxide synthase (PTGS)2 in arterial thrombosis has been well established, whereas its impact in venous thrombosis remains unclear. Here, we showed that PTGS2 deletion predisposes to venous thrombosis as suggested by greater clot firmness and clot elasticity, by higher plasma levels of functional fibrinogen, factor VIII and PAI-1 activity, and proved by bigger thrombi detected after inferior vena cava ligation (IVCL) compared to WT mice. Read More

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http://dx.doi.org/10.1160/TH16-12-0968DOI Listing
July 2017
7 Reads

Lipoprotein MPT83 Induces Apoptosis of Infected Macrophages by Activating the TLR2/p38/COX-2 Signaling Pathway.

J Immunol 2017 06 15;198(12):4772-4780. Epub 2017 May 15.

Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China;

Tuberculosis caused by continues to pose a serious global health threat. The attenuated bacillus Calmette-Guérin, as the only licensed vaccine, has limited protective efficacy against TB. The development of more effective antituberculosis vaccines is urgent and demands for further identification and understanding of Ags. Read More

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http://dx.doi.org/10.4049/jimmunol.1700030DOI Listing
June 2017
16 Reads

Role of prostacyclin synthase in carcinogenesis.

Prostaglandins Other Lipid Mediat 2017 Nov 12;133:49-52. Epub 2017 May 12.

Division of Health Chemistry, Department of Healthcare and Regulatory Sciences, School of Pharmacy, Showa University, Tokyo, Japan. Electronic address:

Prostacyclin (PGI) synthase (PGIS) and microsomal prostaglandin (PG) E synthase-1 (PGES-1) functionally couple with inducible cyclooxygenase-2 (COX-2) as their upstream enzymes to produce PGI and PGE, respectively. Non-steroidal anti-inflammatory drugs exert their pharmacological effects including antitumor effects by the inhibition of COX-2 and thereby suppress this PG biosynthesis. PGIS is abundantly expressed in vascular endothelial and smooth muscle cells and was shown to be critical for the regulation of platelet aggregation and vascular tone. Read More

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http://dx.doi.org/10.1016/j.prostaglandins.2017.05.001DOI Listing
November 2017
14 Reads

Honokiol inhibits ultraviolet radiation-induced immunosuppression through inhibition of ultraviolet-induced inflammation and DNA hypermethylation in mouse skin.

Sci Rep 2017 05 10;7(1):1657. Epub 2017 May 10.

Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA.

Ultraviolet (UV) radiation exposure induces immunosuppression, which contributes to the development of cutaneous malignancies. We investigated the effects of honokiol, a phytochemical found in plants of the genus Magnolia, on UVB-induced immunosuppression using contact hypersensitivity (CHS) as a model in C3H/HeN mice. Topical application of honokiol (0. Read More

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http://dx.doi.org/10.1038/s41598-017-01774-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431968PMC
May 2017
22 Reads