1,441 results match your criteria Cyclooxygenase Deficiency


Toll-like receptor-9 (TLR-9) deficiency alleviates optic nerve injury (ONI) by inhibiting inflammatory response in vivo and in vitro.

Authors:
Lu Zhang Xueying Li

Exp Cell Res 2020 Jul 8:112159. Epub 2020 Jul 8.

Department of Ophthalmology, Shaanxi Provincial People's Hospital, Xi'an, 710068, China. Electronic address:

Traumatic optic neuropathy is a common clinical problem. Damage to the optic nerve leads to shear stress and triggers secondary swelling within the optic canal. The study aims to explore the role of the inflammatory response following optic nerve injury (ONI) in toll-like receptor-9 knockout mice (TLR-9) compared to wild-type mice (WT). Read More

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http://dx.doi.org/10.1016/j.yexcr.2020.112159DOI Listing

A novel pyrazolo [3,4-d] pyrimidine, KKC080106, activates the Nrf2 pathway and protects nigral dopaminergic neurons.

Exp Neurol 2020 Jun 21;332:113387. Epub 2020 Jun 21.

Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address:

The transcription factor nuclear factor-erythroid 2-related factor-2 (Nrf2) is known to induce neuroprotective and anti-inflammatory effects and is considered to be an excellent molecular target for drugs related to neurodegenerative disease therapy. Nrf2 activators previously tested in clinical trials were electrophilic, causing adverse effects due to non-selective and covalent modification of cellular thiols. In order to circumvent this issue, we constructed and screened a chemical library consisting of 241 pyrazolo [3,4-d] pyrimidine derivatives and discovered a novel, non-electrophilic compound: 1-benzyl-6-(methylthio)-N-(1-phenylethyl)-1H-pyrazolo[3,4-d]pyrimidine-4-amine (KKC080106). Read More

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http://dx.doi.org/10.1016/j.expneurol.2020.113387DOI Listing

Effects of thromboxane prostanoid receptor deficiency on diabetic nephropathy induced by high fat diet and streptozotocin in mice.

Eur J Pharmacol 2020 Jun 15;882:173254. Epub 2020 Jun 15.

Cardiovascular Research Center, Shantou University Medical College, Shantou, China. Electronic address:

Diabetic nephropathy (DN), one of the main causes of end-stage renal disease, still remains as a challenge of clinical management. This study aimed to determine whether deficiency of the thromboxane (TX) prostanoid receptor (TP), which mediates the contractile activities of all prostanoids, alleviates the development of DN and if so, to examine the underlying mechanism(s). Diabetes was induced by high fat diet and streptozotocin injection in wild-type (WT) mice and those with TP deficiency (TP). Read More

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http://dx.doi.org/10.1016/j.ejphar.2020.173254DOI Listing

Hyaluronic acid promotes Lgr5 stem cell proliferation and crypt fission through TLR4 and PGE transactivation of EGFR.

Am J Physiol Gastrointest Liver Physiol 2020 Jul 15;319(1):G63-G73. Epub 2020 Jun 15.

Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri.

Hyaluronic acid (HA), a glycosaminoglycan in the extracellular matrix, binds to CD44 and Toll-like receptor 4 (TLR4). We previously demonstrated that both CD44 and TLR4, but predominately TLR4, mediated HA stimulation of Lgr5 stem cell proliferation, crypt fission, and intestinal growth in postnatal mice. Here we address the questions of which cell type expresses the relevant TLR4 in driving intestinal growth and what are the downstream events from TLR4 activation. Read More

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http://dx.doi.org/10.1152/ajpgi.00242.2019DOI Listing

Synthesis, Characterization, Molecular docking, and Biological Activities of Some Natural and Synthetic Urolithin Analogues.

Chem Biodivers 2020 Jun 4. Epub 2020 Jun 4.

Dogu Akdeniz Universitesi, Chemistry, Famagusta TRNC, via Mersin 10, TURKEY.

Urolithins (i.e., hydroxyl substituted benzo[c]chromen-6-one derivatives) are formed within the gastrointestinal tract following to the exposure to various ellagitannin rich diet, particularly involving pomegranate, nuts, and berries. Read More

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http://dx.doi.org/10.1002/cbdv.202000197DOI Listing

PE_PGRS31-S100A9 Interaction Promotes Mycobacterial Survival in Macrophages Through the Regulation of NF-κB-TNF-α Signaling and Arachidonic Acid Metabolism.

Front Microbiol 2020 8;11:845. Epub 2020 May 8.

Hubei Province Key Laboratory of Allergy and Immunology, Department of Immunology, Wuhan University School of Basic Medical Sciences and Department of Allergy, Zhongnan Hospital, Wuhan University, Wuhan, China.

() evades the surveillance of immune responses for survival in macrophages. However, the precise mechanism and toxins/proteins encoded by involved in the bacterial escape remain elusive. The function of Rv1768 protein (also referred to as PE_PGRS31, belonging to the PE_PGRS family) encoded by the region of deletion 14 (RD-14) in the virulent H37Rv strain has not, to the best of our knowledge, been reported previously. Read More

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http://dx.doi.org/10.3389/fmicb.2020.00845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225313PMC
May 2020
3.941 Impact Factor

Selective deficiency in endothelial PTP1B protects from diabetes and endoplasmic reticulum stress-associated endothelial dysfunction via preventing endothelial cell apoptosis.

Biomed Pharmacother 2020 Jul 14;127:110200. Epub 2020 May 14.

Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA, USA; Department of Medicine (Cardiology), Medical College of Georgia, Augusta University, Augusta, GA, USA. Electronic address:

Diabetes notably increases the risk for endothelial dysfunction, a main precursor for microvascular complications. While endoplasmic reticulum stress (ERS) and protein tyrosine phosphatase 1B (PTP1B) have been associated with endothelial dysfunction in resistance vessels, whether these mechanisms also contribute to diabetes-mediated endothelial dysfunction in conduit arteries remains unknown. Herein, we tested the hypothesis that diabetes induces macrovascular endothelial dysfunction via endothelial ERS-induced, PTP1B-mediated apoptosis. Read More

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http://dx.doi.org/10.1016/j.biopha.2020.110200DOI Listing

Environmental aircraft noise aggravates oxidative DNA damage, granulocyte oxidative burst and nitrate resistance in mice.

Free Radic Res 2020 Apr 24;54(4):280-292. Epub 2020 Apr 24.

Center for Cardiology I, Molecular Cardiology, University Medical Center Mainz, Mainz, Germany.

Large epidemiological studies point towards a link between the incidence of arterial hypertension, ischaemic heart disease, metabolic disease and exposure to traffic noise, supporting the role of noise exposure as an independent cardiovascular risk factor. We characterised the underlying molecular mechanisms leading to noise-dependent adverse effects on the vasculature and myocardium in an animal model of aircraft noise exposure and identified oxidative stress and inflammation as central players in mediating vascular and cardiac dysfunction. Here, we studied the impact of noise-induced oxidative DNA damage on vascular function in DNA-repair deficient 8-oxoguanine glycosylase knockout () mice. Read More

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http://dx.doi.org/10.1080/10715762.2020.1754410DOI Listing

Nephron-Specific Disruption of Polycystin-1 Induces Cyclooxygenase-2-Mediated Blood Pressure Reduction Independent of Cystogenesis.

J Am Soc Nephrol 2020 Jun 16;31(6):1243-1254. Epub 2020 Apr 16.

Division of Nephrology, University of Utah Health Center, Salt Lake City, Utah

Background: Hypertension often occurs before renal function deteriorates in autosomal dominant polycystic kidney disease (ADPKD). It is unknown whether the gene product polycystin-1-the predominant causal factor in ADPKD-itself contributes to ADPKD hypertension independent of cystogenesis.

Methods: We induced nephron-specific disruption of the gene in 3-month-old mice and examined them at 4-5 months of age. Read More

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http://dx.doi.org/10.1681/ASN.2019090934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269346PMC

Molecular and Cellular Differences in Cardiac Repair of Male and Female Mice.

J Am Heart Assoc 2020 Apr 16;9(8):e015672. Epub 2020 Apr 16.

Division of Cardiovascular Sciences Department of Medicine University of South Florida Tampa FL.

Background Leukocyte-directed biosynthesis of specialized proresolving mediators (SPMs) orchestrates physiological inflammation after myocardial infarction. Deficiency of SPMs drives pathological and nonresolving inflammation, leading to heart failure (HF). Differences in SPMs and inflammatory responses caused by sex-specific differences are of interest. Read More

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http://dx.doi.org/10.1161/JAHA.119.015672DOI Listing

Genetic Deficiency of the Histamine H-Receptor Reduces Experimental Colorectal Carcinogenesis in Mice.

Cancers (Basel) 2020 Apr 8;12(4). Epub 2020 Apr 8.

Institute of Pharmacology, Hannover Medical School, 30625 Hannover, Germany.

Colorectal cancer (CRC), a severe complication of inflammatory bowel diseases, is a common type of cancer and accounts for high mortality. CRC can be modeled in mice by application of the tumor promoter, azoxymethane (AOM), in combination with dextran sodium sulfate (DSS), which are able to induce colitis-like manifestations. Active colitis correlates with high mucosal concentrations of histamine, which, together with the histamine receptor subtype 4 (HR), provide a pro-inflammatory function in a mouse colitis model. Read More

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http://dx.doi.org/10.3390/cancers12040912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226035PMC

The mechanism of Tyk2 deficiency-induced immunosuppression in mice involves robust IL-10 production in macrophages.

Cytokine 2020 Mar 21;130:155077. Epub 2020 Mar 21.

Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan. Electronic address:

Macrophages are highly plastic in their pro-inflammatory/anti-inflammatory roles. Type I and II interferons (IFNs) are known to modulate macrophage activation. Tyrosine kinase 2 (Tyk2) has an intimate relationship with type I and II IFN signaling. Read More

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http://dx.doi.org/10.1016/j.cyto.2020.155077DOI Listing

Exercise training attenuates cardiac inflammation and fibrosis in hypertensive ovariectomized rats.

J Appl Physiol (1985) 2020 Apr 12;128(4):1033-1043. Epub 2020 Mar 12.

School of Rehabilitation Medicine, Weifang Medical University, Shandong, China.

This study investigated the effects of exercise training on cardiac inflammatory and cardiac fibrotic pathways in female spontaneously hypertensive rats (SHR), which were divided into a sham-operated sedentary hypertensive group (SHR-S), a sedentary hypertensive ovariectomized group (SHR-O), or a hypertensive ovariectomized group with treadmill exercise training (SHR-OT; 60 min/day, 5 days/wk) for 8 wk. Normotensive female Wistar-Kyoto rats (WKY) served as controls. SOD and catalase (CAT) activities were significantly increased in the SHR-OT group, when compared with the SHR-S or SHR-O groups. Read More

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http://dx.doi.org/10.1152/japplphysiol.00844.2019DOI Listing

Fresh Showed a Positive Effect on Mitigating Dextran Sulfate Sodium-Induced Experimental Colitis in Mice.

J Med Food 2020 Apr 28;23(4):459-464. Epub 2020 Feb 28.

Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education, Chongqing, P.R. China.

This study was to compare the anticolitis activity of fresh (FSS) with heated (HSS) with dextran sulfate sodium (DSS)-induced experimental colitis mouse model. Both FSS- and HSS-fed colitis mice exhibited the effects of the increase in the body weight, the alleviation in the colon shortening, and the reduction of the ratio of colon weight to length. However, FSS-fed colitis mice showed a much more significant decrease in DSS-induced tissue damage by mucosal edema and crypt deficiency than did HSS-fed ones. Read More

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http://dx.doi.org/10.1089/jmf.2019.4502DOI Listing

12/15-Lipoxygenase Deficiency Impairs Neutrophil Granulopoiesis and Lung Proinflammatory Responses to .

J Immunol 2020 Apr 26;204(7):1849-1858. Epub 2020 Feb 26.

Department of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, LA 70112

Development of invasive aspergillosis correlates with impairments in innate immunity. We and others have recently shown that arachidonic acid metabolism pathways, specifically the cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) pathways, participate in the induction of protective innate immune responses during invasive aspergillosis. Based on the high degree of cooperation and interconnection within the eicosanoid network, we hypothesized that 12/15-LOX is also active during invasive aspergillosis. Read More

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http://dx.doi.org/10.4049/jimmunol.1900808DOI Listing

Selenium and selenoproteins in prostanoid metabolism and immunity.

Crit Rev Biochem Mol Biol 2019 12 30;54(6):484-516. Epub 2020 Jan 30.

Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, PA, USA.

Selenium (Se) is an essential trace element that functions in the form of the 21st amino acid, selenocysteine (Sec) in a defined set of proteins. Se deficiency is associated with pathological conditions in humans and animals, where incorporation of Sec into selenoproteins is reduced along with their expression and catalytic activity. Supplementation of Se-deficient population with Se has shown health benefits suggesting the importance of Se in physiology. Read More

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http://dx.doi.org/10.1080/10409238.2020.1717430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122104PMC
December 2019

Molecular Classification of Gastric Cancer among Alaska Native People.

Cancers (Basel) 2020 Jan 13;12(1). Epub 2020 Jan 13.

Oncology and Hematology, Alaska Native Medical Center, 4315 Diplomacy Drive, Anchorage, AK 99508, USA.

Gastric cancer is an aggressive and heterogeneous malignancy that often varies in presentation and disease among racial and ethnic groups. The Alaska Native (AN) people have the highest incidence and mortality rates of gastric cancer in North America. This study examines molecular markers in solid tumor samples from eighty-five AN gastric adenocarcinoma patients using next-generation sequencing, immunohistochemistry, and in situ hybridization analysis. Read More

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http://dx.doi.org/10.3390/cancers12010198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016562PMC
January 2020

Resveratrol modulates the blood plasma levels of Cu and Zn, the antioxidant status and the vascular response of thoracic arteries in copper deficient Wistar rats.

Toxicol Appl Pharmacol 2020 Mar 7;390:114877. Epub 2020 Jan 7.

Division of Food Science, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.

Copper (Cu) deficiency plays an important role in the development of cardiovascular disorders. Resveratrol (RSV) possesses pleiotropic cardiovascular benefits; however, the mechanism(s) by which RSV exerts protective effects are not completely understood. Male Wistar rats at 6 weeks of age were fed for 8 weeks with a Cu deficient diet (no added Cu, Cu = 0). Read More

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http://dx.doi.org/10.1016/j.taap.2020.114877DOI Listing
March 2020
3.705 Impact Factor

Cyclooxygenase activity in bradykinin-induced dermal extravasation. A study in mice and humans.

Biomed Pharmacother 2020 Mar 23;123:109797. Epub 2019 Dec 23.

Institute of Pharmacology andClinical Pharmacology, University Hospital, Heinrich Heine University, Düsseldorf, Germany. Electronic address:

Background: Non-allergic angioedema is largely driven by increased plasma levels of bradykinin and over-activation of bradykinin receptor type II (B2), but the specific downstream signalling pathways remain unclear. The aim of this study was to identify signal transduction events involved in bradykinin-induced dermal extravasation.

Methods: Quantification of dermal extravasation was accomplished following intradermal (i. Read More

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http://dx.doi.org/10.1016/j.biopha.2019.109797DOI Listing

Growth hormone-releasing hormone (GHRH) deficiency promotes inflammation-associated carcinogenesis.

Pharmacol Res 2020 02 23;152:104614. Epub 2019 Dec 23.

Department of Pharmacy, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy.

The somatotropic axis, in addition to its well-known metabolic and endocrine effects, plays a pivotal role in modulation of inflammation. Moreover, growth hormone (GH)-releasing hormone (GHRH) has been involved in the development of various human tumors. In this work we aimed to investigate the consequences of GHRH deficiency on the development of inflammation-associated colon carcinogenesis in a mouse model of isolated GH deficiency due to generalized ablation of the GHRH gene [GHRH knock out (GHRHKO)]. Read More

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http://dx.doi.org/10.1016/j.phrs.2019.104614DOI Listing
February 2020

PAR2 deficiency enhances myeloid cell-mediated immunosuppression and promotes colitis-associated tumorigenesis.

Cancer Lett 2020 01 14;469:437-446. Epub 2019 Nov 14.

Department of Gastroenterology, Peking University First Hospital, Beijing, China. Electronic address:

Protease-activated receptor 2 (PAR2) is a member of G-protein coupled receptors, which is widely expressed in intestinal epithelium and immune cells and plays critical roles in intestinal homeostasis. Activation of PAR2 has been implicated in inflammatory process and carcinogenesis. However, it remains unclear whether and how endogenous PAR2 affects colorectal tumorigenesis. Read More

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http://dx.doi.org/10.1016/j.canlet.2019.11.015DOI Listing
January 2020

Altered cyclooxygenase-1 and enhanced thromboxane receptor activities underlie attenuated endothelial dilatory capacity of omental arteries in obesity.

Life Sci 2019 Dec 6;239:117039. Epub 2019 Nov 6.

Qatar Analytics and BioResearch Lab, Anti-Doping Lab Qatar, Qatar. Electronic address:

Aims: Obesity is a risk factor for endothelial dysfunction, the severity of which is likely to vary depending on extent and impact of adiposity on the vasculature. This study investigates the roles of cyclooxygenase isoforms and thromboxane receptor activities in the differential endothelial dilatory capacities of arteries derived from omental and subcutaneous adipose tissues in obesity.

Main Methods: Small arteries were isolated from omental and subcutaneous adipose tissues obtained from consented morbidly obese patients (n = 65, BMI 45 ± 6 kg m [Mean ± SD]) undergoing bariatric surgery. Read More

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http://dx.doi.org/10.1016/j.lfs.2019.117039DOI Listing
December 2019
2.702 Impact Factor

Mice lacking DGKε show increased beige adipogenesis in visceral white adipose tissue after long-term high fat diet in a COX-2- dependent manner.

Adv Biol Regul 2020 01 5;75:100659. Epub 2019 Oct 5.

Department of Anatomy and Cell Biology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata City, Yamagata, 9909585, Japan.

Adipose tissue is a central site for energy storage in the form of triglyceride (TG). Under excess energy conditions, TG is synthesized by acylation of diacylglycerol (DG), whereas TG is broken down into DG and free fatty acid, which provide energy for mitochondrial lipid oxidation when needed. In this regard, DG is not merely an intermediate metabolite for TG metabolism; it also serves as a signaling molecule. Read More

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http://dx.doi.org/10.1016/j.jbior.2019.100659DOI Listing
January 2020
1 Read

Cell-Specific Gene Deletion Reveals the Antithrombotic Function of COX1 and Explains the Vascular COX1/Prostacyclin Paradox.

Circ Res 2019 10 12;125(9):847-854. Epub 2019 Sep 12.

From the National Heart and Lung Institute, Imperial College London, United Kingdom (J.A.M., F.S., Y.E., N.S.K.).

Rationale: Endothelial cells (ECs) and platelets, which respectively produce antithrombotic prostacyclin and prothrombotic thromboxane A, both express COX1 (cyclooxygenase1). Consequently, there has been no way to delineate any antithrombotic role for COX1-derived prostacyclin from the prothrombotic effects of platelet COX1. By contrast, an antithrombotic role for COX2, which is absent in platelets, is straightforward to demonstrate. Read More

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http://dx.doi.org/10.1161/CIRCRESAHA.119.314927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791564PMC
October 2019

Pharmaco-Genetic Screen To Uncover Actin Regulators Targeted by Prostaglandins During Oogenesis.

G3 (Bethesda) 2019 11 5;9(11):3555-3565. Epub 2019 Nov 5.

Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242

Prostaglandins (PGs) are lipid signaling molecules with numerous physiologic functions, including pain/inflammation, fertility, and cancer. PGs are produced downstream of cyclooxygenase (COX) enzymes, the targets of non-steroidal anti-inflammatory drugs (NSAIDs). In numerous systems, PGs regulate actin cytoskeletal remodeling, however, their mechanisms of action remain largely unknown. Read More

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http://dx.doi.org/10.1534/g3.119.400704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829128PMC
November 2019
2 Reads

JmjC domain-containing protein 8 (JMJD8) represses Ku70/Ku80 expression via attenuating AKT/NF-κB/COX-2 signaling.

Authors:
Yao Su Jun Wang

Biochim Biophys Acta Mol Cell Res 2019 12 29;1866(12):118541. Epub 2019 Aug 29.

Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Chinese Academy of Sciences, Hefei 230031, China. Electronic address:

Jumonji C (JmjC) domain-containing proteins have been shown to regulate cellular processes by hydroxylating or demethylating histone and non-histone targets. JMJD8 is a Jumonji C domain-containing protein localized in the lumen of the endoplasmic reticulum and was recently shown to be involved in endothelial differentiation and cellular inflammation response. However, other physiological functions of JMJD8 remain to be elucidated. Read More

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http://dx.doi.org/10.1016/j.bbamcr.2019.118541DOI Listing
December 2019
2 Reads

Loss in efficacy measures of tolfenamic acid in a tau knock-out model: Relevance to Alzheimer's disease.

Exp Biol Med (Maywood) 2019 10 26;244(13):1062-1069. Epub 2019 Aug 26.

Interdisciplinary Neuroscience Program, University of Rhode Island, Kingston, RI 02881, USA.

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http://dx.doi.org/10.1177/1535370219871249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775567PMC
October 2019
3 Reads

Combination of schisandrin and nootkatone exerts neuroprotective effect in Alzheimer's disease mice model.

Metab Brain Dis 2019 12 17;34(6):1689-1703. Epub 2019 Aug 17.

School of Functional Food and wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, People's Republic of China.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases which seriously affect the quality of life of the elderly. Schisandrin (SCH) and nootkatone (NKT) are the two marked active components in ASHP. In this study, the effects of Alpinia oxyphylla-Schisandra chinensis herb pair (ASHP) as well as its bioactive components on cognitive deficiency and dementia were revealed via Aβ-induced AD in mouse. Read More

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http://dx.doi.org/10.1007/s11011-019-00475-4DOI Listing
December 2019
3 Reads
2.638 Impact Factor

Influence of iron-deficient diets during gestation and lactation on cerebral fatty acids and eicosanoids in guinea pig offspring-Comparison of studies with different sources of dietary lipids.

Prostaglandins Leukot Essent Fatty Acids 2019 10 9;149:37-45. Epub 2019 Aug 9.

Département de Chimie et Biochimie, Université de Moncton, 18 Antonine-Maillet Avenue, Moncton, NB, E1A 3E9, Canada. Electronic address:

Previous studies showed that mild iron deficiency anaemia (IDA) induced by feeding an iron deficient (ID) diet to female guinea pigs during gestation and lactation to alters the auditory functions of the offspring when corn oil is the only source of dietary lipids. Conversely, feeding an ID diet with a dietary fatty acid composition similar to that of typical human western diets induced minor impairments. Since tissue fatty acid metabolism is affected by dietary iron, the current study measured the impacts of these ID diets (ID-corn and ID-west) compared to the corresponding iron-sufficient control diets (IS-corn and IS-west) on encephalum fatty acid metabolism in the offspring at post-natal day 24. Read More

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http://dx.doi.org/10.1016/j.plefa.2019.08.001DOI Listing
October 2019
3 Reads

Loss of hypothermic and anti-pyretic action of paracetamol in cyclooxygenase-1 knockout mice is indicative of inhibition of cyclooxygenase-1 variant enzymes.

Eur J Pharmacol 2019 Oct 14;861:172609. Epub 2019 Aug 14.

Centre for Biochemical Pharmacology, William Harvey Research Institute, Bart's and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, EC1M 6BQ, London, UK.

Paracetamol (acetaminophen), is a centrally-acting antipyretic analgesic drug, which can also lower body temperature. Despite a century of clinical use, its mechanism of pharmacological action has not been completely elucidated. Previously, we demonstrated significant attenuation in the paracetamol induced hypothermia in parallel with its inhibitory action on the synthesis of brain prostaglandin E (PGE) in cyclooxygenase-1 (COX-1) knockout mice in comparison to wild-type mice. Read More

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http://dx.doi.org/10.1016/j.ejphar.2019.172609DOI Listing
October 2019

Inhibition of osteoclastogenesis by mechanically stimulated osteoblasts is attenuated during estrogen deficiency.

Am J Physiol Cell Physiol 2019 11 14;317(5):C969-C982. Epub 2019 Aug 14.

Mechanobiology and Medical Devices Research Group, Centre for Biomechanics Research, Biomedical Engineering, College of Engineering and Informatics, National University of Ireland, Galway, Ireland.

Osteoporotic bone loss and fracture have long been regarded to arise upon depletion of circulating estrogen, which increases osteoclastogenesis and bone resorption. Osteoblasts from human osteoporotic patients also display deficient osteogenic responses to mechanical loading. However, while osteoblasts play an important role in regulating osteoclast differentiation, how this relationship is affected by estrogen deficiency is unknown. Read More

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http://dx.doi.org/10.1152/ajpcell.00168.2019DOI Listing
November 2019
1 Read

Early B Cell Factor 1 (EBF1) Regulates Glomerular Development by Controlling Mesangial Maturation and Consequently COX-2 Expression.

J Am Soc Nephrol 2019 09 12;30(9):1559-1572. Epub 2019 Aug 12.

Department of Orthopedics and Rehabilitation and

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. EBF1 is present within multiple glomerular cell types, including the glomerular mesangium and podocytes.

Methods: To identify which cell type is driving the glomerular developmental defects in the global EBF1 knockout mice, we deleted EBF1 from the mesangium/pericytes (Foxd1-cre) or podocytes (Podocin-cre) in mice. Read More

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http://dx.doi.org/10.1681/ASN.2018070699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727263PMC
September 2019
1 Read

Regulation of YAP by Mammalian Target of Rapamycin Complex 1 in Endothelial Cells Controls Blood Pressure Through COX-2/mPGES-1/PGE Cascade.

Hypertension 2019 10 5;74(4):936-946. Epub 2019 Aug 5.

From the Tianjin Key Laboratory of Metabolic Diseases, Key Laboratory of Immune Microenvironment and Disease-Ministry of Education, Department of Physiology and Pathophysiology, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin, Medical University, China (L.Y., J.H., B.L., M.Y., H.W., M.L., X.L., H.L., X.Z., Y.Z., D.A.).

Endothelial cells regulate vascular tone by producing both relaxing and contracting factors to control the local blood flow. Hypertension is a common side effect of mTORC1 (mammalian target of rapamycin complex 1) inhibitors. However, the role of endothelial mTORC1 in hypertension remains elusive. Read More

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.12834DOI Listing
October 2019
2 Reads

Increased pain and inflammatory sensitivity in growth hormone-releasing hormone (GHRH) knockout mice.

Prostaglandins Other Lipid Mediat 2019 10 10;144:106362. Epub 2019 Jul 10.

Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.

Growth hormone (GH) and GH-releasing hormone (GHRH), in addition to metabolic and endocrine effects, play a role in the modulation of pain and inflammation. We aimed to elucidate the consequences of GHRH deficiency on acute nociceptive stimulation and on both acute and chronic inflammatory stimuli in a mouse model of GH deficiency. Mice with generalized ablation of the GHRH gene (GHRH knock out, GHRHKO, -/-) were compared to wild type (GHRH +/+) mice. Read More

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http://dx.doi.org/10.1016/j.prostaglandins.2019.106362DOI Listing
October 2019
18 Reads

Abnormal Expression of Leads to Dysregulation of Inflammatory Effectors in Human Synoviocytes.

Mediators Inflamm 2019 28;2019:6768504. Epub 2019 May 28.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi'an, Shaanxi, China.

Dysregulation of multiple microRNAs widely takes place during rheumatoid arthritis (RA) and experimental arthritides. This study is performed to explore the possible mechanism underlying deficiency-mediated inflammation in human synoviocytes SW982. Firstly, RNAi of led to increased COX2, MMP3, and MMP13 protein production, while overexpression could reduce MMP13 expression. Read More

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http://dx.doi.org/10.1155/2019/6768504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558604PMC
January 2020
4 Reads
3.236 Impact Factor

Platelet-Specific Deletion of Cyclooxygenase-1 Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice.

J Pharmacol Exp Ther 2019 09 27;370(3):416-426. Epub 2019 Jun 27.

Department of Neuroscience, Imaging, and Clinical Sciences and Center for Research on Aging and Translational Medicine, "G. d'Annunzio" University School of Medicine, Chieti, Italy (A.Sa., A.B., A.C., M.D., S.T., P.G.-L., T.S., L.D.F., R.F., P.B., S.A., P.P.); Department of Systems Pharmacology and Translational Therapeutics and Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (E.R., G.A.F.); Departments of General Pathology (V.A., A.Sg.) and Pharmacology (C.P.), Catholic University School of Medicine, Rome, Italy; Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China (G.L., Y.G.); and Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China (Y.Y.)

Inflammatory bowel disease (IBD) is associated with an increased risk for thromboembolism, platelet activation, and abnormalities in platelet number and size. In colitis, platelets can extravasate into the colonic interstitium. We generated a mouse with a specific deletion of cyclooxygenase (COX)-1 in megakaryocytes/platelets [(COX-1 conditional knockout (cKO)] to clarify the role of platelet activation in the development of inflammation and fibrosis in dextran sodium sulfate (DSS)-induced colitis. Read More

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http://dx.doi.org/10.1124/jpet.119.259382DOI Listing
September 2019
5 Reads

Activation of a protumorigenic IFNγ/STAT1/IRF-1 signaling pathway in keratinocytes following exposure to solar ultraviolet light.

Mol Carcinog 2019 09 25;58(9):1656-1669. Epub 2019 Jun 25.

Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas.

In this study, we evaluated the role of signal transducer and activator of transcription 1 (STAT1) in response to acute solar ultraviolet (SUV) radiation in mouse epidermis. Analysis of the epidermis from SUV-irradiated mice revealed rapid phosphorylation of STAT1 (pSTAT1) on both tyrosine (tyr701) and serine (ser727) residues and increased levels of IRF-1 while later timepoints showed increased levels of unphosphorylated STAT1 (uSTAT1). STAT1 activation led to upregulation of several proinflammatory chemokine mRNAs in epidermis including Cxcl9, Cxcl10, and Ccl2, as well as, the immune checkpoint inhibitor Pd-l1. Read More

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http://dx.doi.org/10.1002/mc.23073DOI Listing
September 2019
3 Reads

15-Deoxy-Δ12,14-Prostaglandin J Reinforces the Anti-Inflammatory Capacity of Endothelial Cells With a Genetically Determined NO Deficit.

Circ Res 2019 07 19;125(3):282-294. Epub 2019 Jun 19.

From the Department of Cardiovascular Physiology, Heidelberg University (I.U., M.T., S.G., M.R.M., A.H.W., C.R., M.H.).

Rationale: Fluid shear stress (FSS) maintains NOS-3 (endothelial NO synthase) expression. Homozygosity for the C variant of the T-786C single-nucleotide polymorphism of the NOS3 gene, which solely exists in humans, renders the gene less sensitive to FSS, resulting in a reduced endothelial cell (EC) capacity to generate NO. Decreased bioavailability of NO in the arterial vessel wall facilitates atherosclerosis. Read More

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http://dx.doi.org/10.1161/CIRCRESAHA.118.313820DOI Listing
July 2019
8 Reads

Microglial-targeting induced by intranasal linalool during neurological protection postischemia.

Eur J Pharmacol 2019 Aug 25;857:172420. Epub 2019 May 25.

Neuroscience Group of Antioquia, Cellular and Molecular Neurobiology Area. School of Medicine, SIU, University of Antioquia, Calle 70 # 52-21, Medellín, Colombia. Electronic address:

Stroke is the second cause of death and first cause of physical disability around the world; it affects the brain parenchyma through oxygen deficiency and spreads excitotoxicity. The complexity of the disease has made it difficult to find effective therapies. It is necessary to identify new treatments that effectively act within the narrow therapeutic window but also offer long-term protection poststroke. Read More

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http://dx.doi.org/10.1016/j.ejphar.2019.172420DOI Listing
August 2019
5 Reads

Reduced inflammatory state promotes reinnervation of endometriotic-like lesions in TNFRp55 deficient mice.

Mol Hum Reprod 2019 07;25(7):385-396

Laboratorio de Biología de la Reproducción (LABIR), Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis (IMIBIO-SL-CONICET), Ejército de Los Andes 950, CP D5700HHW, San Luis, Argentina.

Endometriosis is a chronic gynecological disease, characterized by growth of endometrial tissue in ectopic sites due to alteration of peritoneal homeostasis and deregulation of apoptosis. Here we have examined whether TNFRp55 deficiency modulates the pro-inflammatory state and the reinnervation of endometriotic-like lesions in mice. Two-month-old female C57BL/6 mice, eight wild type (WT) and eight TNFRp55-/- (KO) were used in the study. Read More

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http://dx.doi.org/10.1093/molehr/gaz026DOI Listing
July 2019
2 Reads

Serotonin synthesis protects the mouse colonic crypt from DNA damage and colorectal tumorigenesis.

J Pathol 2019 09 27;249(1):102-113. Epub 2019 Jun 27.

Department of Toxicology, Bromatology, and Clinical Analysis, University of Sao Paulo, Ribeirao Preto, Brazil.

Serotonin (5-HT) signaling pathways are thought to be involved in colorectal tumorigenesis (CRT), but the role of 5-HT synthesis in the early steps of this process is presently unknown. In this study, we used carcinogen treatment in the tryptophan hydroxylase 1 knockout (Tph1KO) and transgenic (Tph1 Villin ) mouse models defective in 5-HT synthesis to investigate the early mutagenic events associated with CRT. Our observations of the colonic crypt post-treatment followed a timeline designed to understand how disruption of 5-HT synthesis affects the initial steps leading to CRT. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/path.5285
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http://dx.doi.org/10.1002/path.5285DOI Listing
September 2019
32 Reads

Endometriosis.

Endocr Rev 2019 08;40(4):1048-1079

Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

Pelvic endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects primarily pelvic tissues, including the ovaries. It is caused when shed endometrial tissue travels retrograde into the lower abdominal cavity. Endometriosis is the most common cause of chronic pelvic pain in women and is associated with infertility. Read More

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http://dx.doi.org/10.1210/er.2018-00242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693056PMC
August 2019
7 Reads
21.059 Impact Factor

Maternal vitamin D deficiency increases the thromboxane/prostacyclin ratio through alterations in the one-carbon cycle in Wistar rats.

Biofactors 2019 Jul 15;45(4):548-555. Epub 2019 Apr 15.

Department of Nutritional Medicine, Mother and Child Health, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth, Pune Satara Road, Pune, 411043, Maharashtra, India.

This study aims to test the hypothesis that vitamin D deficiency can influence long-chain polyunsaturated fatty acid metabolism through alterations in the one-carbon cycle. Wistar rats (n = 8 per group) were given either a control (1,000 IU D3/kg diet) or a vitamin D deficient (VDD) (0 IU D3/kg diet) diet from pre-pregnancy to delivery. On day 20 of gestation, pregnant female rats were delivered by C-section to collect placenta and blood. Read More

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http://dx.doi.org/10.1002/biof.1510DOI Listing
July 2019
4 Reads

P2X7 receptor deletion suppresses γ-radiation-induced hyposalivation.

Am J Physiol Regul Integr Comp Physiol 2019 05 20;316(5):R687-R696. Epub 2019 Mar 20.

Department of Nutritional Sciences, The University of Arizona , Tucson, Arizona.

Head and neck cancer treatments typically involve a combination of surgery and radiotherapy, often leading to collateral damage to nearby tissues causing unwanted side effects. Radiation damage to salivary glands frequently leads to irreversible dysfunction by poorly understood mechanisms. The P2X7 receptor (P2X7R) is a ligand-gated ion channel activated by extracellular ATP released from damaged cells as "danger signals. Read More

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http://dx.doi.org/10.1152/ajpregu.00192.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589606PMC
May 2019
9 Reads

Loss of NF-κB p50 function synergistically augments microglial priming in the middle-aged brain.

J Neuroinflammation 2019 Mar 12;16(1):60. Epub 2019 Mar 12.

Department of Anatomy and Cell Biology, The Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.

Background: While NF-κB p50 function is impaired in central nervous system disease, aging in non-CNS tissues, and response to reactive oxygen species, the role of NF-κB p50 in aging-associated microglial pro-inflammatory priming is poorly understood.

Methods: Male NF-κB p50 and NF-κB p50 mice at three different ages (1.5-3. Read More

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https://jneuroinflammation.biomedcentral.com/articles/10.118
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http://dx.doi.org/10.1186/s12974-019-1446-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419422PMC
March 2019
8 Reads

Microglia-Derived Adiposomes are Potential Targets for the Treatment of Ischemic Stroke.

Cell Mol Neurobiol 2019 Jul 9;39(5):591-604. Epub 2019 Mar 9.

Department of Life Sciences, National Chung Hsing University, 145, Xingda Road, Taichung, 402, Taiwan, ROC.

It is known that cerebral ischemia can cause brain inflammation and adiposome can serve as a depot of inflammatory mediators. In the study, the pro-inflammatory and pro-death role of adiposome in ischemic microglia and ischemic brain was newly investigated. The contribution of PPARγ to adiposome formation was also evaluated for the first time in ischemic microglia. Read More

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http://dx.doi.org/10.1007/s10571-019-00665-9DOI Listing
July 2019
11 Reads

MicroRNA-30d deficiency during preconception affects endometrial receptivity by decreasing implantation rates and impairing fetal growth.

Am J Obstet Gynecol 2019 07 28;221(1):46.e1-46.e16. Epub 2019 Feb 28.

Igenomix S.L., Valencia, Spain; Department of Pediatrics, Obstetrics and Gynecology, Universidad de Valencia, INCLIVA, Valencia, Spain; Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Stanford, CA.

Background: Maternal-embryonic crosstalk between the endometrium and the preimplantation embryo is required for normal pregnancy. Our previous results demonstrated that maternal microRNAs secreted into the endometrial fluid, specifically miR-30d, act as a transcriptomic regulator of the preimplantation embryo by the maternal intrauterine environment.

Objective: To investigate the reproductive and fetal effects of murine miR-30d deficiency at the maternal-embryonic interface according to the origin of its maternal or embryonic default. Read More

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http://dx.doi.org/10.1016/j.ajog.2019.02.047DOI Listing
July 2019
11 Reads

CCR5 is a required signaling receptor for macrophage expression of inflammatory genes in response to viral double-stranded RNA.

Am J Physiol Regul Integr Comp Physiol 2019 05 27;316(5):R525-R534. Epub 2019 Feb 27.

Department of Biochemistry, Medical College of Wisconsin , Milwaukee, Wisconsin.

Double-stranded (ds) RNA, both synthetic and produced during virus replication, rapidly stimulates MAPK and NF-κB signaling that results in expression of the inflammatory genes inducible nitric oxide synthase, cyclooxygenase 2, and IL-1β by macrophages. Using biochemical and genetic approaches, we have identified the chemokine ligand-binding C-C chemokine receptor type 5 (CCR5) as a cell surface signaling receptor required for macrophage expression of inflammatory genes in response to dsRNA. Activation of macrophages by synthetic dsRNA does not require known dsRNA receptors, as poly(inosinic:cytidylic) acid [poly(I:C)] activates signaling pathways leading to expression of inflammatory genes to similar levels in wild-type and Toll-like receptor 3- or melanoma differentiation antigen 5-deficient macrophages. Read More

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http://dx.doi.org/10.1152/ajpregu.00019.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589596PMC
May 2019
4 Reads

CRISPR/Cas9 Editing of Glia Maturation Factor Regulates Mitochondrial Dynamics by Attenuation of the NRF2/HO-1 Dependent Ferritin Activation in Glial Cells.

J Neuroimmune Pharmacol 2019 12 27;14(4):537-550. Epub 2019 Feb 27.

Harry S. Truman Memorial Veteans Hospital, Columbia, MO, USA.

Microglial cells are brain specific professional phagocytic immune cells that play a crucial role in the inflammation- mediated neurodegeneration especially in Parkinson's disease (PD) and Alzheimer's disease. Glia maturation factor (GMF) is a neuroinflammatory protein abundantly expressed in the brain. We have previously shown that GMF expression is significantly upregulated in the substantia nigra (SN) of PD brains. Read More

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http://dx.doi.org/10.1007/s11481-019-09833-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711834PMC
December 2019
12 Reads

β-arrestin 2 negatively regulates NOD2 signalling pathway through association with TRAF6 in microglia after cerebral ischaemia/reperfusion injury.

J Cell Mol Med 2019 05 22;23(5):3325-3335. Epub 2019 Feb 22.

Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, P.R. China.

We previously reported that nucleotide-binding oligomerization domain-containing protein (NOD) 2 was involved in the inflammatory responses to cerebral ischaemia/reperfusion (I/R) insult. However, the mechanism by which NOD2 participates in brain ischaemic injury and the regulation of NOD2 in the process are still obscure. Increased β-arrestin 2 (ARRB2) expression was observed in microglia following cerebral I/R in wild-type mice besides the up-regulation of NOD2 and TRAF6. Read More

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http://dx.doi.org/10.1111/jcmm.14223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484299PMC
May 2019
9 Reads