50 results match your criteria cytosporone csn-b

Histone Deacetylase Inhibitor Improves the Dysfunction of Hippocampal Gamma Oscillations and Fast Spiking Interneurons in Alzheimer's Disease Model Mice.

Front Mol Neurosci 2021 23;14:782206. Epub 2021 Dec 23.

Pain and Neuroscience, Drug Discovery and Disease Research Laboratory, Shionogi & Co., Ltd., Osaka, Japan.

The hippocampal gamma oscillation is important for cognitive function, and its deficit is related to cognitive impairment in Alzheimer's disease (AD). Recently, it has been recognized that post-translational modification via histone acetylation is a fundamental molecular mechanism for regulating synaptic plasticity and cognitive function. However, little is known regarding the regulation of hippocampal gamma oscillation by histone acetylation. Read More

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December 2021

Cytosporone B (Csn-B), an NR4A1 agonist, attenuates acute cardiac allograft rejection by inducing differential apoptosis of CD4+T cells.

Int Immunopharmacol 2022 Jan 10;104:108521. Epub 2022 Jan 10.

Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

CD4+T cell-mediated acute rejection remains a major factor that affects the early survival of transplanted organs post-transplantation. Here, we reveal that nuclear receptor subfamily 4 Group A member 1 (Nr4A1) was upregulated during cardiac allograft rejection and that the increased Nr4A1 was primarily localized in intragraft-infiltrating CD4+T cells. Nr4A1 acts as a transcription factor with an important role in CD4+T cell apoptosis, differentiation and T cell dysfunction, which indicates that Nr4A1 may play a critical role in transplant rejection. Read More

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January 2022

[Nur77 inhibits the proliferation of prostate cancer cells].

Zhonghua Nan Ke Xue 2021 Jul;27(7):589-594

Department of Urology, Zhongda Hospital Affiliated to Southeast University, Nanjing, Jiangsu 210009, China.

Objective: To study the effects of Nur77 on prostate cancer (PCa) cell growth and its potential value in the treatment of PCa.

Methods: We detected the expression of the NUR77 protein in human PCa tissues and cells by Western blot and determined the effects of Nur77 on the proliferation and apoptosis of the PCa cells by flow cytometry.

Results: Nur77 and AR were expressed in the human PCa tissue and cells, and overexpressed NUR77 inhibited the proliferation and cell cycle progression of the PCa LNCaP cells. Read More

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Inflammatory Monocyte Counts Determine Venous Blood Clot Formation and Resolution.

Arterioscler Thromb Vasc Biol 2021 12 16:ATVBAHA121317176. Epub 2021 Dec 16.

Department of Dermatology, Westfälische Wilhelms-University Münster, Germany

Background: Monocytes are thought to be involved in venous thrombosis but the role of individual monocyte subpopulations on thrombus formation, clot inflammation, and degradation is an important unresolved issue. We investigate the role of inflammatory Ly6C monocytes in deep vein thrombosis and their potential therapeutic impact.

Methods: Frequencies and compositions of blood monocytes were analyzed by flow cytometry in CCR2 (C-C chemokine receptor type 2) and wild-type mice of different ages and after treatment with the NR4A1 (nuclear receptor group 4 family A member 1, Nur77) agonist CnsB (cytosporone B). Read More

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December 2021

Nr4A1 modulates inflammation-associated intestinal fibrosis and dampens fibrogenic signaling in myofibroblasts.

Am J Physiol Gastrointest Liver Physiol 2021 09 21;321(3):G280-G297. Epub 2021 Jul 21.

Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.

Intestinal fibrosis is a common complication of the inflammatory bowel diseases (IBDs), contributing to tissue stiffening and luminal narrowing. Human nuclear receptor 4A 1 (NR4A1) was previously reported to regulate mesenchymal cell function and dampen fibrogenic signaling. NR4A1 gene variants are associated with IBD risk, and it has been shown to regulate intestinal inflammation. Read More

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September 2021

Orphan nuclear receptor 4A1 (NR4A1) and novel ligands.

Essays Biochem 2021 Dec;65(6):877-886

Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, U.S.A.

The nuclear receptor (NR) superfamily of transcription factors encodes expression of 48 human genes that are important for maintaining cellular homeostasis and in pathophysiology, and this has been observed for all sub-families including orphan receptors for which endogenous ligands have not yet been identified. The orphan NR4A1 (Nur77 and TR3) and other members of this sub-family (NR4A2 and NR4A3) are immediate early genes induced by diverse stressors, and these receptors play an important role in the immune function and are up-regulated in some inflammatory diseases including solid tumors. Although endogenous ligands for NR4A have not been identified, several different classes of compounds have been characterized as NR4A1 ligands that bind the receptor. Read More

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December 2021

The NR4A agonist, Cytosporone B, attenuates pro-inflammatory mediators in human colorectal cancer tissue ex vivo.

Biochem Biophys Res Commun 2021 05 30;554:179-185. Epub 2021 Mar 30.

School of Veterinary Medicine, University College Dublin, Dublin, Ireland; Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland. Electronic address:

Inflammation is a pivotal pathological factor in colorectal cancer (CRC) initiation and progression, and modulating this inflammatory state has the potential to ameliorate disease progression. NR4A receptors have emerged as key regulators of inflammatory pathways that are important in CRC. Here, we have examined the effect of NR4A agonist, Cytosporone B (CsnB), on colorectal tissue integrity and its effect on the inflammatory profile in CRC tissue ex vivo. Read More

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Assessment of NR4A Ligands That Directly Bind and Modulate the Orphan Nuclear Receptor Nurr1.

J Med Chem 2020 12 8;63(24):15639-15654. Epub 2020 Dec 8.

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, Florida 33458, United States.

Nurr1/NR4A2 is an orphan nuclear receptor transcription factor implicated as a drug target for neurological disorders including Alzheimer's and Parkinson's diseases. Previous studies identified small-molecule NR4A nuclear receptor modulators, but it remains unclear if these ligands affect transcription via direct binding to Nurr1. We assessed 12 ligands reported to affect NR4A activity for Nurr1-dependent and Nurr1-independent transcriptional effects and the ability to bind the Nurr1 ligand-binding domain (LBD). Read More

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December 2020

Blocking PPARγ interaction facilitates Nur77 interdiction of fatty acid uptake and suppresses breast cancer progression.

Proc Natl Acad Sci U S A 2020 11 21;117(44):27412-27422. Epub 2020 Oct 21.

State Key Laboratory of Cellular Stress Biology, State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, School of Life Sciences, Xiamen University, 361005 Xiamen, Fujian Province, China

Nuclear receptor Nur77 participates in multiple metabolic regulations and plays paradoxical roles in tumorigeneses. Herein, we demonstrated that the knockout of Nur77 stimulated mammary tumor development in two mouse models, which would be reversed by a specific reexpression of Nur77 in mammary tissues. Mechanistically, Nur77 interacted and recruited corepressors, the SWI/SNF complex, to the promoters of and to suppress their transcriptions, which hampered the fatty acid uptake, leading to the inhibition of cell proliferation. Read More

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November 2020

Nuclear Receptor Subfamily 4 Group A Member 1 Overexpression Prolongs Free Flap Allotransplant Graft Survival by Inducing T-Cell Anergy in the Rat.

Transplant Proc 2021 Jan-Feb;53(1):474-480. Epub 2020 Sep 9.

Department of Plastic Surgery, Xijing Hospital, Air Force Medical University, Xi'an, Shanxi Province, China. Electronic address:

Background: New strategies to inhibit acute rejection are needed for further applications of composite tissue allotransplantation. The nuclear receptor subfamily 4 group A member 1 (NR4A1) is considered a key controller of maintaining tolerance homeostasis. However, the effect of NR4A1 in suppressing rejection responses after allotransplantation remains unknown. Read More

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Nur77 attenuates inflammatory responses and oxidative stress by inhibiting phosphorylated IκB-α in Parkinson's disease cell model.

Aging (Albany NY) 2020 05 13;12(9):8107-8119. Epub 2020 May 13.

Department of Neurology, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, P.R. China.

Neuroinflammation and oxidative stress play key roles in the pathological development of Parkinson's disease (PD). Nerve growth factor-induced gene B (Nur77) is closely related to dopamine neurotransmission, and its pathogenesis is unclear. This study aims to investigate the role and mechanism of Nur77 in a cell model of Parkinson's disease. Read More

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Reactivation of NR4A1 Restrains Chondrocyte Inflammation and Ameliorates Osteoarthritis in Rats.

Front Cell Dev Biol 2020 17;8:158. Epub 2020 Mar 17.

Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Osteoarthritis (OA) is the most prevalent joint disease and uncontrolled inflammation is now recognized to play vital roles in OA development. Targeting the endogenous counterpart of inflammation may develop new therapeutic approaches in resolving inflammation persistence and treating inflammatory disease including OA. The orphan nuclear receptor 4A1 (NR4A1) is a key negative regulator of inflammatory responses but its role in osteoarthritis remains unclear. Read More

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Nr4a1 suppresses cocaine-induced behavior via epigenetic regulation of homeostatic target genes.

Nat Commun 2020 01 24;11(1):504. Epub 2020 Jan 24.

Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Endogenous homeostatic mechanisms can restore normal neuronal function following cocaine-induced neuroadaptations. Such mechanisms may be exploited to develop novel therapies for cocaine addiction, but a molecular target has not yet been identified. Here we profiled mouse gene expression during early and late cocaine abstinence to identify putative regulators of neural homeostasis. Read More

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January 2020

A new phenol derivative isolated from mangrove-derived fungus sp. HJ002.

Nat Prod Res 2021 Nov 21;35(21):4051-4057. Epub 2020 Jan 21.

Key Laboratory of Tropical Medicinal Plant Chemistry of Ministry of Education, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou, Hainan, China.

A new phenol derivative, 3-chloro-5-hydroxy-4-methoxyphenylacetic acid methyl ester (), along with five known compounds methyl 4-hydroxyphenylacetate (), cytosporone B (), ()-striatisporolide A (), ()-butanedioic acid () and ergosterol () were isolated from the mangrove-derived fungus sp. HJ002. Their structures were established by spectroscopic methods, GIAO based C NMR chemical shift calculations and comparison with the data of literature. Read More

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November 2021

Nur77-activated lncRNA WFDC21P attenuates hepatocarcinogenesis via modulating glycolysis.

Oncogene 2020 03 20;39(11):2408-2423. Epub 2020 Jan 20.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, 361102, Fujian, PR China.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Orphan nuclear receptor Nur77, which is low expressed in HCC, functions as a tumor suppressor to suppress HCC. However, the detailed mechanism is still not well understood. Read More

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An Accord of Nuclear Receptor Expression in CD4 T Cells in Rheumatoid Arthritis.

Immunohorizons 2019 08 22;3(8):402-411. Epub 2019 Aug 22.

CSIR-Institute of Microbial Technology, Chandigarh 160036, India; and

Chronically activated CD4 T cells drive uncontrolled inflammation, leading to tissue damage in various autoimmune disorders, such as rheumatoid arthritis (RA). Investigation of the molecular mechanisms involved in RA and recent analysis of transcriptomic profiles has implicated members of the nuclear receptor (NR) superfamily in RA. NRs are required for the development, differentiation, and effector function of CD4 T cells; therefore, it is thought that NRs are important in shaping the CD4 T cell repertoire and associated inflammation in RA. Read More

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Orphan nuclear receptor NR4A1 suppresses hyperhomocysteinemia-induced hepatic steatosis in vitro and in vivo.

FEBS Lett 2019 05 22;593(10):1061-1071. Epub 2019 Apr 22.

Department of Cell Biology and Genetics, Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, China.

Homocysteine (Hcy) is associated with nonalcoholic fatty liver disease (NAFLD). orphan nuclear receptor subfamily 4 group A member 1 (NR4A1) is involved in hepatic lipid metabolism. However, the potential role of NR4A1 in Hcy-associated NAFLD remains elusive. Read More

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Cytosporone B as a Biological Preservative: Purification, Fungicidal Activity and Mechanism of Action against .

Biomolecules 2019 03 29;9(4). Epub 2019 Mar 29.

Key Laboratory of Plant Resource Conservation and Sustainable Utilization, Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China.

To prevent citrus decay caused by , 12 natural products were isolated from two endophytic fungi, in which cytosporone B was shown to have excellent bioactivity for control of with median effect concentration (EC) of 26.11 μg/mL and minimum inhibitory concentration (MIC) of 105 μg/mL, and also significantly reduced the decay of sugar orange during the in vivo trials. In addition, cytosporone B could alter the morphology of by causing distortion of the mycelia and loss of membrane integrity. Read More

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The effects of cytosporone-B, a novel antifibrotic agent, on vocal fold fibroblasts.

Laryngoscope 2018 12 16;128(12):E425-E428. Epub 2018 Oct 16.

Department of Otolaryngology-Head and Neck Surgery, New York University Voice Center, New York University School of Medicine, New York, New York, U.S.A.

Objectives/hypothesis: Our laboratory recently described NR4A1 as an endogenous inhibitor of TGF-β-induced vocal fold (VF) fibrosis. Our prior report described the temporal expression of NR4A1 during VF healing in vivo and the effects of NR4A1 knockdown on fibroplastic cell activities in vitro. Based on these findings, we hypothesized that cytosporone-B (Csn-B), an NR4A1 agonist, may hold significant therapeutic potential. Read More

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December 2018

Hypoxia/reperfusion predisposes to atherosclerosis.

PLoS One 2018 5;13(10):e0205067. Epub 2018 Oct 5.

Skin and Endothelium Research Division (SERD), Department of Dermatology, Medical University of Vienna, Vienna, Austria.

Surgical interventions on blood vessels bear a risk for intimal hyperplasia and atherosclerosis as a consequence of injury. A specific feature of intimal hyperplasia is the loss of vascular smooth muscle cell (VSMC) differentiation gene expression. We hypothesized that immediate responses following injury induce vascular remodeling. Read More

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Characteristics of Nur77 and its ligands as potential anticancer compounds (Review).

Mol Med Rep 2018 12 27;18(6):4793-4801. Epub 2018 Sep 27.

College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, P.R. China.

Nuclear receptor subfamily 4 group A member 1 (NR4A1; also termed Nur77/TR3/NGFIB), a member of the nuclear receptor superfamily, is expressed as an early response gene to regulate the expression of multiple target genes. Nur77 has the typical structure of a nuclear receptor, including an N‑terminal domain, a DNA binding domain, and a ligand‑binding domain. The expression and localization of Nur77 are closely associated with its roles in cell proliferation and apoptosis. Read More

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December 2018

Oxidized analogs of Di(1-indol-3-yl)methyl-4-substituted benzenes are NR4A1-dependent UPR inducers with potent and safe anti-cancer activity.

Oncotarget 2018 May 18;9(38):25057-25074. Epub 2018 May 18.

Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, USA.

Di(1-indol-3-yl)(4-trifluoromethylphenyl)methane (DIM-Ph-4-CF) is an analog of orphan nuclear receptor 4A1 (NR4A1) ligand cytosporone B. We have synthesized several oxidation products of DIM-Ph-4-CF, focusing on analogs with electron-withdrawing or donating groups at their phenyl ring 4-positions, and examined their anti-cancer activity and mechanism-of-action. Mesylates (DIM-Ph-4-X OMss) having CF, COMe and Cl groups were more effective inhibitors of cancer cell viability than their precursors. Read More

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NR4A1 is Involved in Fibrogenesis in Ovarian Endometriosis.

Cell Physiol Biochem 2018 13;46(3):1078-1090. Epub 2018 Apr 13.

Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background/aims: Excess fibrosis may lead to chronic pain, scarring, and infertility as endometriosis develops and progresses. The pathogenesis of endometriosis has been linked to transforming growth factor-β (TGF-β), the most potent promoter of fibrosis.

Methods: Levels of NR4A1 and P-NR4A1 protein in human endometrial and endometriotic tissue were assessed by western blotting and immunohistochemistry. Read More

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Treatment with the NR4A1 agonist cytosporone B controls influenza virus infection and improves pulmonary function in infected mice.

PLoS One 2017 20;12(10):e0186639. Epub 2017 Oct 20.

Laboratory of Innate Immunology, Centre de recherche du CHU de Québec-Université Laval (CHUL) and Department of Molecular Medicine, Université Laval, Quebec, QC, Canada.

The transcription factor NR4A1 has emerged as a pivotal regulator of the inflammatory response and immune homeostasis. Although contribution of NR4A1 in the innate immune response has been demonstrated, its role in host defense against viral infection remains to be investigated. In the present study, we show that administration of cytosporone B (Csn-B), a specific agonist of NR4A1, to mice infected with influenza virus (IAV) reduces lung viral loads and improves pulmonary function. Read More

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November 2017

TR3 is involved in hypoxia-induced apoptosis resistance in lung cancer cells downstream of HIF-1α.

Lung Cancer 2017 09 21;111:15-22. Epub 2017 Jun 21.

Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria; Institute of Physiology, Medical University of Graz, Graz, Austria. Electronic address:

Objectives: Lung cancer is the leading cause of cancer death worldwide. Like in all solid tumors, hypoxia is common in lung cancer and contributes to apoptosis, and thus chemotherapy resistance. However, the underlying mechanisms are not entirely clear. Read More

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September 2017

Activation of Nur77 in microglia attenuates proinflammatory mediators production and protects dopaminergic neurons from inflammation-induced cell death.

J Neurochem 2017 02 21;140(4):589-604. Epub 2016 Dec 21.

Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.

Microglia-mediated neuroinflammation plays a critical role in the pathological development of Parkinson's disease (PD). Orphan nuclear receptor Nur77 (Nur77) is abundant in neurons, while its role in microglia-mediated neuroinflammation remains unclear. The present data demonstrated that the expression of Nur77 in microglia was reduced accompanied by microglia activation in response to lipopolysaccharide (LPS) in vitro and in experimental 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-PD mouse model. Read More

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February 2017

Nur77 downregulation triggers pulmonary artery smooth muscle cell proliferation and migration in mice with hypoxic pulmonary hypertension via the Axin2-β-catenin signaling pathway.

Vascul Pharmacol 2016 12 15;87:230-241. Epub 2016 Nov 15.

Jiangsu Key Laboratory of Organ Transplantation, Wuxi People's Hospital Affiliated to Nanjing Medical University, PR China; Department of Cardiothoracic Surgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, PR China; Lung Transplant Group, Wuxi People's Hospital Affiliated to Nanjing Medical University, PR China. Electronic address:

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by remodeling of the pulmonary vasculature, including marked proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs). Members of the nuclear receptor 4A (NR4A) subfamily are involved in a variety of biological events, such as cell apoptosis, proliferation, inflammation, and metabolism. Activation of Nur77 (an orphan nuclear receptor that belongs to NR4A subfamily) has recently been reported to be as a beneficial agent in the treatment of cardiovascular and metabolic diseases. Read More

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December 2016

Nur77 attenuates endothelin-1 expression via downregulation of NF-κB and p38 MAPK in A549 cells and in an ARDS rat model.

Am J Physiol Lung Cell Mol Physiol 2016 Dec 7;311(6):L1023-L1035. Epub 2016 Oct 7.

Department of Intensive Care Medicine, Youjiang Medical University for Nationalities, Baise, Guangxi, China

Acute respiratory distress syndrome (ARDS) is characterized by inflammatory injury to the alveolar and capillary barriers that results in impaired gas exchange and severe acute respiratory failure. Nuclear orphan receptor Nur77 has emerged as a regulator of gene expression in inflammation, and its role in the pathogenesis of ARDS is not clear. The objective of this study is to investigate the potential role of Nur77 and its underlying mechanism in the regulation of endothelin-1 (ET-1) expression in lipopolysaccharide (LPS)-induced A549 cells and an ARDS rat model. Read More

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December 2016

NR4A1-dependent Ly6C monocytes contribute to reducing joint inflammation in arthritic mice through Treg cells.

Eur J Immunol 2016 12 18;46(12):2789-2800. Epub 2016 Oct 18.

Laboratory of Innate Immunology, Centre de recherche du CHU de Québec-Université Laval, Québec, QC, Canada.

Monocytes are central to the physiopathology of arthritis, but their roles in progression and resolution of the disease remain to be clarified. Using NR4A1 mice, which lack patrolling lymphocyte antigen 6C (Ly6C ) monocytes, we found that inflammatory Ly6C monocytes contribute to rapid development of arthritis in a serum transfer-induced arthritis (STIA) model. Our experiments suggest that patrolling monocytes do not promote the initiation and progression of arthritis in mice, as severity of symptoms was amplified in NR4A1 mice. Read More

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December 2016

Nur77 exacerbates PC12 cellular injury in vitro by aggravating mitochondrial impairment and endoplasmic reticulum stress.

Sci Rep 2016 Sep 29;6:34403. Epub 2016 Sep 29.

Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Tianhe Road 600, Guangzhou, Guangdong 510630, P.R. China.

The nuclear orphan receptor, Nur77 plays important roles in neuroimflammation, apoptosis, and dopaminergic neurodegeneration. We conducted a further mechanistic investigation into the association of Nur77 with cell death. Cytosporone B (Csn-B), an agonist for Nur77, and Nur77 knockdown were adopted in the 6-hydroxydopamine (OHDA)-lesioned PC12 cells to investigate the mechanisms underlying Nur77-mediated injury. Read More

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September 2016