1,518 results match your criteria Cyclooxygenase Deficiency

Gut dysbacteriosis attenuates resistance to infection by decreasing Cyclooxygenase 2 to inhibit endoplasmic reticulum stress.

Emerg Microbes Infect 2022 Jun 29:1-31. Epub 2022 Jun 29.

College of Veterinary Medicine, China Agricultural University, Beijing, China.

The role of gut microbiota has been described as an important influencer of the immune system. Gut-lung axis is critical in the prevention of mycobacterium infection, but the specific mechanism by which dysbiosis affects tuberculosis have not been reported. In this study, we attempted to provide more information on how the gut-lung axis contributes to Mycobacterium bovis () infection. Read More

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Exploring and Verifying the Mechanism and Targets of Shenqi Pill in the Treatment of Nonalcoholic Steatohepatitis via Network Pharmacology and Experiments.

J Immunol Res 2022 12;2022:6588144. Epub 2022 Jun 12.

The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China.

Shenqi pill (SQP), a famous traditional Chinese medicine (TCM) herbal formula derived from Jinguiyaolue (Synopsis of Prescriptions of the Golden Chamber), has long been used to treat kidney yang deficiency syndrome. According to the TCM treatment principle that the liver and kidney are homologies, the clinical use of SQP in the treatment of nonalcoholic steatohepatitis (NASH) has achieved a good effect. However, the active targeted genes and underlying mechanism remain unclear. Read More

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COX-2 Deficiency Promotes White Adipogenesis via PGE2-Mediated Paracrine Mechanism and Exacerbates Diet-Induced Obesity.

Cells 2022 06 2;11(11). Epub 2022 Jun 2.

Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.

Cyclooxygenase-2 (COX-2) plays a critical role in regulating innate immunity and metabolism by producing prostaglandins (PGs) and other lipid mediators. However, the implication of adipose COX-2 in obesity remains largely unknown. Using adipocyte-specific COX-2 knockout (KO) mice, we showed that depleting COX-2 in adipocytes promoted white adipose tissue development accompanied with increased size and number of adipocytes and predisposed diet-induced adiposity, obesity, and insulin resistance. Read More

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Interleukin 17A deficiency alleviates neuroinflammation and cognitive impairment in an experimental model of diabetic encephalopathy.

Neural Regen Res 2022 Dec;17(12):2771-2777

Department of Physiology, School of Medicine, and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China.

Interleukin 17A (IL-17A) was previously shown to be a key pro-inflammatory factor in diabetes mellitus and associated complications. However, the role of IL-17A in diabetic encephalopathy remains poorly understood. In this study, we established a mouse model of diabetic encephalopathy that was deficient in IL-17A by crossing Il17a mice with spontaneously diabetic Ins2 (Akita) mice. Read More

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December 2022

Lipocalin 2 Deficiency Alters Prostaglandin Biosynthesis and mTOR Signaling Regulation of Thermogenesis and Lipid Metabolism in Adipocytes.

Cells 2022 05 3;11(9). Epub 2022 May 3.

Department of Food Science and Nutrition, University of Minnesota, Twin Cities, MN 55455, USA.

Apart from a well-known role in the innate immune system, lipocalin 2 (Lcn2) has been recently characterized as a critical regulator of thermogenesis and lipid metabolism. However, the physiological mechanism through which Lcn2 regulates cellular metabolism and thermogenesis in adipocytes remains unknown. We found that Lcn2 expression and secretion are significantly upregulated by arachidonic acid (AA) and mTORC1 inhibition in differentiated inguinal adipocytes. Read More

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OLFM4 deficiency delays the progression of colitis to colorectal cancer by abrogating PMN-MDSCs recruitment.

Oncogene 2022 05 29;41(22):3131-3150. Epub 2022 Apr 29.

Department of Neurosurgery, Affiliated Dongguan Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, China.

Chronic inflammatory bowel disease (IBD) is strongly associated with the development of colitis-associated tumorigenesis (CAT). Despite recent advances in the understanding of polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) responses in cancer, the mechanisms of these cells during this process remain largely uncharacterized. Here, we discovered a glycoprotein, olfactomedin-4 (OLFM4), was highly expressed in PMN-MDSCs from colitis to colorectal cancer (CRC), and its expression level and PMN-MDSC population positively correlated with the progression of IBD to CRC. Read More

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Genetic BACH1 deficiency alters mitochondrial function and increases NLRP3 inflammasome activation in mouse macrophages.

Redox Biol 2022 05 10;51:102265. Epub 2022 Feb 10.

Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany. Electronic address:

BTB-and-CNC homologue 1 (BACH1), a heme-regulated transcription factor, mediates innate immune responses via its functional role in macrophages. BACH1 has recently been shown to modulate mitochondrial metabolism in cancer cells. In the current study, we utilized a proteomics approach and demonstrate that genetic deletion of BACH1 in mouse macrophages is associated with decreased levels of various mitochondrial proteins, particularly mitochondrial complex I. Read More

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Promotion of the inflammatory response in mid colon of complement component 3 knockout mice.

Sci Rep 2022 02 1;12(1):1700. Epub 2022 Feb 1.

Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, 50463, Korea.

To determine whether complement component 3 (C3) deficiency affects its receptor downstream-mediated inflammatory response, the current study was undertaken to measure alterations in the inducible nitric oxide synthase (iNOS)‑mediated cyclooxygenase‑2 (COX‑2) induction pathway, inflammasome pathway, nuclear factor-κB (NF-κB) activation, and inflammatory cytokine expressions in the mid colon of C3 knockout (KO) mice. Significant enhancement was observed in expressions of key components of the iNOS‑mediated COX‑2 induction pathway, and in the phosphorylation of mitogen‑activated protein (MAP) kinase members. A similar pattern of increase was also observed in the expression levels of inflammasome proteins in C3 KO mice. Read More

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February 2022

Current and Emerging Approaches for Pain Management in Hemophilic Arthropathy.

Pain Ther 2022 Mar 12;11(1):1-15. Epub 2022 Jan 12.

Università degli Studi di Milano, Dipartimento di Fisiopatologia e Medicina dei Trapianti, Via Pace, 9, 20122, Milan, Italy.

Introduction: Hemophilia is an inherited bleeding hematological disorder characterized by the partial or complete deficiency of clotting factor VIII or IX. Hemophilic arthropathy is the consequence of repeated joint bleeding (hemarthrosis) and its management is based on the prevention of acute bleeding through the administration of the deficient clotting factor concentrate or non-factor therapies. In addition, the management of acute and chronic pain is pivotal in hemophilic arthropathy in order to restore function and allow rehabilitation of the joint. Read More

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Cyclooxygenase-2 deficiency attenuates lipopolysaccharide-induced inflammation, apoptosis, and acute lung injury in adult mice.

Am J Physiol Regul Integr Comp Physiol 2022 02 5;322(2):R126-R135. Epub 2022 Jan 5.

Department of Pediatrics, Vanderbilt University, Nashville, Tennessee.

Many lung diseases are caused by an excessive inflammatory response, and inflammatory lung diseases are often modeled using lipopolysaccharide (LPS) in mice. Cyclooxygenase-2 (COX-2) encoded by the gene is induced in response to inflammatory stimuli including LPS. The objective of this study was to test the hypothesis that mice deficient in COX-2 () will be protected from LPS-induced lung injury. Read More

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February 2022

Facilitation of colonic T cell immune responses is associated with an exacerbation of dextran sodium sulfate-induced colitis in mice lacking microsomal prostaglandin E synthase-1.

Inflamm Regen 2022 Jan 4;42(1). Epub 2022 Jan 4.

Department of Regulation Biochemistry, Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Sagamihara, 252-0373, Japan.

Background: Microsomal prostaglandin E synthase-1 (mPGES-1) is a key enzyme that acts downstream of cyclooxygenase and plays a major role in inflammation by converting prostaglandin (PG) H to PGE. The present study investigated the effect of genetic deletion of mPGES-1 on the development of immunologic responses to experimental colitis induced by dextran sodium sulfate (DSS), a well-established model of inflammatory bowel disease (IBD).

Methods: Colitis was induced in mice lacking mPGES-1 (mPGES-1 mice) and wild-type (WT) mice by administering DSS for 7 days. Read More

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January 2022

Ca-independent phospholipase Aβ-derived PGE contributes to osteogenesis.

Prostaglandins Other Lipid Mediat 2022 02 16;158:106605. Epub 2021 Dec 16.

Department of Cell, Developmental, and Integrative Biology, USA; Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address:

Bone modeling can be modulated by lipid signals such as arachidonic acid (AA) and its cyclooxygenase 2 (COX2) metabolite, prostaglandin E (PGE), which are recognized mediators of optimal bone formation. Hydrolysis of AA from membrane glycerophospholipids is catalyzed by phospholipases A (PLAs). We reported that mice deficient in the Ca- independent PLAbeta (iPLAβ), encoded by Pla2g6, exhibit a low bone phenotype, but the cause for this remains to be identified. Read More

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February 2022

Inhibition of the Interaction of TREM-1 and eCIRP Attenuates Inflammation and Improves Survival in Hepatic Ischemia/Reperfusion.

Shock 2022 02;57(2):246-255

Department of Surgery, Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York.

Introduction: Triggering receptor expressed on myeloid cells-1 (TREM-1) has important implications in sepsis and inflammation and is a novel receptor for extracellular cold-inducible RNA-binding protein (eCIRP). We hypothesize that the inhibition of TREM-1 via its interaction with eCIRP by novel peptide inhibitor M3 or knockout gene will attenuate the inflammation and injury associated with severe hepatic ischemia/reperfusion (I/R).

Methods: Wild-type (WT) C57BL/6 and TREM-1-/- mice underwent 60 min of 70% hepatic ischemia, with 24 h of reperfusion. Read More

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February 2022

Effects of dietary zinc deficiency on esophageal squamous cell proliferation and the mechanisms involved.

World J Gastrointest Oncol 2021 Nov;13(11):1755-1765

Department of Gastroenterology, Beijing Shijitan Hospital Affiliated to Capital Medical University, Beijing 100038, China.

Background: Dietary zinc deficiency has been shown to be associated with the development of esophageal cancer in humans, but the exact mechanism of action is not known.

Aim: To observe the effects of dietary zinc deficiency on esophageal squamous cell proliferation.

Methods: Thirty C57BL/6 mice were randomly divided into three groups: A zinc-sufficient (ZS) group, zinc-deficient (ZD) group, and zinc-replenished (ZR) group. Read More

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November 2021

Systems Approach to Integrating Preclinical Apolipoprotein E-Knockout Investigations Reveals Novel Etiologic Pathways and Master Atherosclerosis Network in Humans.

Arterioscler Thromb Vasc Biol 2022 01 11;42(1):35-48. Epub 2021 Nov 11.

Molecular Cardiology Research Institute (R.R.X., M.E.M., B.V.C., Y.W., N.C., A.S., I.Z.J.), Tufts Medical Center, Boston, MA.

Objective: Animal models of atherosclerosis are used extensively to interrogate molecular mechanisms in serial fashion. We tested whether a novel systems biology approach to integration of preclinical data identifies novel pathways and regulators in human disease. Approach and Results: Of 716 articles published in from 1995 to 2019 using the apolipoprotein E knockout mouse to study atherosclerosis, data were extracted from 360 unique studies in which a gene was experimentally perturbed to impact plaque size or composition and analyzed using Ingenuity Pathway Analysis software. Read More

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January 2022

Mixed lineage kinase domain-like pseudokinase-mediated necroptosis aggravates periodontitis progression.

J Mol Med (Berl) 2022 01 13;100(1):77-86. Epub 2021 Oct 13.

Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Department of Periodontics, School of Stomatology, Tongji University, Shanghai, China.

Necroptosis is a form of cell death that is reportedly involved in the pathogenesis of periodontitis. The role of Mlkl-involved necroptosis remains unclear. Herein, this project aimed to explore the role of MLKL-mediated necroptosis in periodontitis in vitro and in vivo. Read More

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January 2022

Influence of Vitamin D on the Vasoactive Effect of Estradiol in a Rat Model of Polycystic Ovary Syndrome.

Int J Mol Sci 2021 Aug 30;22(17). Epub 2021 Aug 30.

Department of Obstetrics and Gynecology, Semmelweis University, Üllői Street 78/a, 1082 Budapest, Hungary.

We examined the vasoactive effect of estradiol in a rat model of early PCOS and the influence of vitamin D deficiency (VDD). We created a model of chronic hyperandrogenism and VDD in adolescent female Wistar rats (N = 46) with four experimental groups: vitamin D supplemented (T-D+), VDD (T-D-), hyperandrogenic and vitamin D supplemented (T+D+), and hyperandrogenic and VDD (T+D-). T+ groups received an 8-week-long transdermal Androgel treatment, D-animals were on vitamin D-reduced diet and D+ rats were supplemented orally with vitamin D3. Read More

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Selenium Deficiency Aggravates Heat Stress Pneumonia in Chickens by Disrupting the M1/M2 Balance.

Biol Trace Elem Res 2022 Jul 4;200(7):3315-3325. Epub 2021 Sep 4.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China.

Selenium (Se) is an essential trace element found in the body. Se deficiency and M1/M2 imbalance are closely related to inflammation. Heat stress can decrease immune function and cause inflammation. Read More

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Mitofusin 2 Deficiency Causes Pro-Inflammatory Effects in Human Primary Macrophages.

Front Immunol 2021 12;12:723683. Epub 2021 Aug 12.

Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany.

Mitofusin 2 (MFN2) is a mitochondrial outer membrane GTPase, which modulates mitochondrial fusion and affects the interaction between endoplasmic reticulum and mitochondria. Here, we explored how MFN2 influences mitochondrial functions and inflammatory responses towards zymosan in primary human macrophages. A knockdown of MFN2 by small interfering RNA decreased mitochondrial respiration without attenuating mitochondrial membrane potential and reduced interactions between endoplasmic reticulum and mitochondria. Read More

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December 2021

Toll-like receptor-4 null mutation causes fetal loss and fetal growth restriction associated with impaired maternal immune tolerance in mice.

Sci Rep 2021 08 16;11(1):16569. Epub 2021 Aug 16.

Robinson Research Institute and Adelaide Medical School, University of Adelaide, Adelaide, SA, 5005, Australia.

Maternal immune adaptation to accommodate pregnancy depends on sufficient availability of regulatory T (Treg) cells to enable embryo implantation. Toll-like receptor 4 is implicated as a key upstream driver of a controlled inflammatory response, elicited by signals in male partner seminal fluid, to initiate expansion of the maternal Treg cell pool after mating. Here, we report that mice with null mutation in Tlr4 (Tlr4) exhibit impaired reproductive outcomes after allogeneic mating, with reduced pregnancy rate, elevated mid-gestation fetal loss, and fetal growth restriction, compared to Tlr4 wild-type controls. Read More

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The Enhanced Inhibitory Effect of Estrogen on PD-L1 Expression Following Nrf2 Deficiency in the AOM/DSS Model of Colitis-Associated Cancer.

Front Oncol 2021 8;11:679324. Epub 2021 Jul 8.

Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea.

Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a dual role in carcinogenesis. We previously reported that Nrf2 deficiency enhances the anti-tumorigenic effect of 17β-estradiol (E2) in an azoxymethane (AOM)/dextran sodium sulfate (DSS) model of colitis-associated cancer (CAC). Herein, we aimed to determine a possible explanation for our recent work and investigated the immune microenvironment represented by programmed death-ligand 1 (PD-L1) expression. Read More

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Isoginkgetin treatment attenuated lipopolysaccharide-induced monoamine neurotransmitter deficiency and depression-like behaviors through downregulating p38/NF-κB signaling pathway and suppressing microglia-induced apoptosis.

J Psychopharmacol 2021 Oct 19;35(10):1285-1299. Epub 2021 Jul 19.

Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, Guangdong, China.

Background: Microglia activation-induced neuroinflammation may contribute to the etiology of depression. containing high concentration of isoginkgetin could effectively treat mental diseases in ancient times. However, the therapeutic role, peculiarly in the brain-immune modulation in depression is still unclear. Read More

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October 2021

A positive COX-2/IL-1β loop promotes decidualization by upregulating CD82.

Reproduction 2021 08 11;162(3):227-236. Epub 2021 Aug 11.

Laboratory for Reproductive Immunology, NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, People's Republic of China.

A successful pregnancy requires sufficient decidualization of endometrial stromal cells (ESCs). CD82, a metastasis suppressor, is a critical regulator for trophoblast invasion but the effect in decidualization was largely unknown. Here we reported that there was a high level of CD82 in DSC by the immunohistochemistry staining and flow cytometer analysis. Read More

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CD147 receptor is essential for TFF3-mediated signaling regulating colorectal cancer progression.

Signal Transduct Target Ther 2021 07 14;6(1):268. Epub 2021 Jul 14.

National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.

Major gaps in understanding the molecular mechanisms of colorectal cancer (CRC) progression and intestinal mucosal repair have hampered therapeutic development for gastrointestinal disorders. Trefoil factor 3 (TFF3) has been reported to be involved in CRC progression and intestinal mucosal repair; however, how TFF3 drives tumors to become more aggressive or metastatic and how TFF3 promotes intestinal mucosal repair are still poorly understood. Here, we found that the upregulated TFF3 in CRC predicted a worse overall survival rate. Read More

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Coordinated pyruvate kinase activity is crucial for metabolic adaptation and cell survival during mitochondrial dysfunction.

Hum Mol Genet 2021 10;30(21):2012-2026

Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm 141 86, Sweden.

Deoxyguanosine kinase (DGUOK) deficiency causes mtDNA depletion and mitochondrial dysfunction. We reported long survival of DGUOK knockout (Dguok-/-) mice despite low (<5%) mtDNA content in liver tissue. However, the molecular mechanisms enabling the extended survival remain unknown. Read More

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October 2021

Metabolipidomic profiling reveals an age-related deficiency of skeletal muscle pro-resolving mediators that contributes to maladaptive tissue remodeling.

Aging Cell 2021 06 2;20(6):e13393. Epub 2021 Jun 2.

Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.

Specialized pro-resolving mediators actively limit inflammation and support tissue regeneration, but their role in age-related muscle dysfunction has not been explored. We profiled the mediator lipidome of aging muscle via liquid chromatography-tandem mass spectrometry and tested whether treatment with the pro-resolving mediator resolvin D1 (RvD1) could rejuvenate the regenerative ability of aged muscle. Aged mice displayed chronic muscle inflammation and this was associated with a basal deficiency of pro-resolving mediators 8-oxo-RvD1, resolvin E3, and maresin 1, as well as many anti-inflammatory cytochrome P450-derived lipid epoxides. Read More

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Ablation of TRPV1 Abolishes Salicylate-Induced Sympathetic Activity Suppression and Exacerbates Salicylate-Induced Renal Dysfunction in Diet-Induced Obesity.

Cells 2021 05 18;10(5). Epub 2021 May 18.

Division of Nanomedicine and Molecular Intervention, Department of Medicine, Michigan State University, East Lansing, MI 48824, USA.

Sodium salicylate (SA), a cyclooxygenase inhibitor, has been shown to increase insulin sensitivity and to suppress inflammation in obese patients and animal models. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel expressed in afferent nerve fibers. Cyclooxygenase-derived prostaglandins are involved in the activation and sensitization of TRPV1. Read More

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Vitamin D stimulates miR-26b-5p to inhibit placental COX-2 expression in preeclampsia.

Sci Rep 2021 05 27;11(1):11168. Epub 2021 May 27.

Department of Physiology, Harbin Medical University, Harbin, 150081, China.

Vitamin D insufficiency or deficiency during pregnancy has been associated with an increased risk of preeclampsia. Increased placental cyclooxygenase-2 (COX-2) activity was proposed to contribute to the inflammatory response in preeclampsia. This study was to investigate if vitamin D can benefit preeclampsia by inhibiting placental COX-2 expression. Read More

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Astrocytes propel neurovascular dysfunction during cerebral cavernous malformation lesion formation.

J Clin Invest 2021 07;131(13)

Department of Medicine, and.

Cerebral cavernous malformations (CCMs) are common neurovascular lesions caused by loss-of-function mutations in 1 of 3 genes, including KRIT1 (CCM1), CCM2, and PDCD10 (CCM3), and generally regarded as an endothelial cell-autonomous disease. Here we reported that proliferative astrocytes played a critical role in CCM pathogenesis by serving as a major source of VEGF during CCM lesion formation. An increase in astrocyte VEGF synthesis is driven by endothelial nitric oxide (NO) generated as a consequence of KLF2- and KLF4-dependent elevation of eNOS in CCM endothelium. Read More

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[Effect of Dendrobium officinale superfine powder on stomach Yin deficiency model mice induced by "spicy overeating"].

Zhongguo Zhong Yao Za Zhi 2021 Apr;46(7):1651-1657

Zhejiang Chinese Medical University Hangzhou 310053, China.

Dendrobium officinale is a traditional Chinese medicine for nourishing Yin and benefiting stomach. Its superfine powder has many advantages, such as good dissolution, high utilization rate, strong integrity and easy to use. However, the researches on effect of D. Read More

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