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https://www.readbyqxmd.com/read/28302649/endothelial-protective-monocyte-patrolling-in-large-arteries-intensified-by-western-diet-and-atherosclerosis
#1
Amado Quintar, Sara McArdle, Dennis Wolf, Alex Marki, Erik Ehinger, Melanie Vassallo, Jacqueline F Miller, Zbigniew Mikulski, Klaus Ley, Konrad Buscher
Rationale: Non-classical mouse monocyte (CX3CR1(high), Ly-6C(low)) patrolling along the vessels of the microcirculation is critical for endothelial homeostasis and inflammation. Due to technical challenges it is currently not established how patrolling occurs in large arteries. Objective: This study was undertaken to elucidate the molecular, migratory and functional phenotype of patrolling monocytes in the high shear and pulsatile environment of large arteries in healthy, hyperlipidemic and atherosclerotic conditions...
March 16, 2017: Circulation Research
https://www.readbyqxmd.com/read/28294325/three-dimensional-culture-of-buffalo-granulosa-cells-in-hanging-drop-mimics-the-preovulatory-follicle-stage
#2
Monica Yadav, Himanshu Agrawal, Mamta Pandey, Dheer Singh, Suneel Kumar Onteru
Granulosa cell (GC) culture models mimicking the intrafollicular environment are limited. Such models have a great potential in reproductive toxicity studies. The buffalo, a monovulatory species like humans, could be a better model than polyovulatory rodents. Therefore, we targeted the development and characterization of three-dimensional (3D) culture systems for buffalo GCs. The GCs from small ovarian follicles (SF) maintained the CYP19 gene expression for 144 h in a 2D culture system. Hence, GCs from SF were cultured directly in 3D using hanging drop and Poly-{(2-hydroxyethyl methacrylate)} (polyHEMA) methods in the DMEM media containing 1ng/mL FSH and 10 ng/mL IGF-1 for 144 h...
March 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28267394/downregulation-of-mir-377-promotes-oral-squamous-cell-carcinoma-growth-and-migration-by-targeting-hdac9
#3
Bhawna Rastogi, Amit Kumar, Satish K Raut, Naresh K Panda, Vidya Rattan, Nainesh Joshi, Madhu Khullar
microRNAs are the post-transcriptional regulators implicated in the initiation and progression of various cancer types, including oral squamous cell carcinoma (OSCC). Here, we investigated the role of miR-377 in OSCC tumorigenesis. miR-377 expression was reduced in OSCC samples and cell line (UPCI-SCC-116), and was associated with patient survival. In vitro restoration of miR-377 repressed cell growth, induced apoptosis, and reduced cell migration. We identified HDAC9 as a target of miR-377 and found miR-377 to regulate HDAC9 and its pro-apoptotic target, NR4A1/Nur77...
March 16, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28249906/nr4a3-suppresses-lymphomagenesis-through-induction-of-pro-apoptotic-genes
#4
Alexander Ja Deutsch, Beate Rinner, Martin Pichler, Katharina Troppan, Katrin Pansy, Marco Bischof, Karoline Fechter, Stefan Hatzl, Julia Feichtinger, Kerstin Wenzl, Marie-Therese Frisch, Verena Stiegelbauer, Andreas Prokesch, Anne Margrethe Krogsdam, Heinz Sill, Gerhard G Thallinger, Hildegard T Greinix, Chenguang Wang, Christine Beham-Schmid, Peter Neumeister
Nuclear orphan receptor NR4A1 exerts an essential tumor suppressor function in aggressive lymphomas. In this study, we investigated the hypothesized contribution of the related NR4A family member NR4A3 to lymphomagenesis. In aggressive lymphoma patients, low expression of NR4A3 was associated with poor survival. Ectopic expression or pharmacological activation of NR4A3 in lymphoma cell lines led to a significantly higher proportion of apoptotic cells. In a mouse NSG xenograft model of lymphoma (stably transduced SuDHL4 cells), NR4A3 expression abrogated tumor growth, compared to vector control and uninduced cells which formed massive tumors...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28198082/pck1-expression-is-correlated-with-the-plasma-glucose-level-in-the-duck
#5
L Chen, T Zeng, G Q Li, R Liu, Y Tian, Q H Li, L Z Lu
Phosphoenolpyruvate carboxykinase 1 (soluble) (PCK1) is a key gene in gluconeogenesis and glyceroneogenesis. Although its functions have been extensively studied in mice, bats and humans, little is known in ducks. Here, PCK1 functions were studied using a duck domestication model and a 48-h fasting experiment. We found PCK1 expression significantly decreased in two breeds of domestic ducks (Jinyun Pockmark ducks and Cherry Valley ducks) as compared with wild ducks (Anas platyrhynchos). Simultaneously, plasma levels of glucose, triglycerides and free fatty acid in domestic ducks were lower than in wild ducks...
February 15, 2017: Animal Genetics
https://www.readbyqxmd.com/read/28167941/nr4a-receptors-differentially-regulate-nf-%C3%AE%C2%BAb-signaling-in-myeloid-cells
#6
Caitriona McEvoy, Monica de Gaetano, Hugh E Giffney, Bojlul Bahar, Eoin P Cummins, Eoin P Brennan, Mary Barry, Orina Belton, Catherine G Godson, Evelyn P Murphy, Daniel Crean
Dysregulation of inflammatory responses is a hallmark of multiple diseases such as atherosclerosis and rheumatoid arthritis. As constitutively active transcription factors, NR4A nuclear receptors function to control the magnitude of inflammatory responses and in chronic inflammatory disease can be protective or pathogenic. Within this study, we demonstrate that TLR4 stimulation using the endotoxin lipopolysaccharide (LPS) rapidly enhances NR4A1-3 expression in human and murine, primary and immortalized myeloid cells with concomitant gene transcription and protein secretion of MIP-3α, a central chemokine implicated in numerous pathologies...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28055275/the-nr4a-subfamily-of-nuclear-receptors-potential-new-therapeutic-targets-for-the-treatment-of-inflammatory-diseases
#7
Ricardo Rodríguez-Calvo, Marta Tajes, Manuel Vázquez-Carrera
Prolonged inflammatory response contributes to the pathogenesis of chronic disease-related disturbances. Among nuclear receptors (NRs), the orphan NR4A subfamily, which includes Nur77 (NR4A1), Nurr1 (NR4A2) and NOR1 (NR4A3), has recently emerged as a therapeutic target for the treatment of inflammation. Areas covered: This review focuses on the capacity of NR4A receptors to counter-regulate the development of the inflammatory response, with a special focus on the molecular transrepression mechanisms. Expert opinion: Recent studies have highlighted the role of NR4A receptors as significant regulators of the inflammatory response...
January 12, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28002729/the-heterogeneity-of-ly6c-hi-monocytes-controls-their-differentiation-into-inos-macrophages-or-monocyte-derived-dendritic-cells
#8
Shinelle Menezes, Daisy Melandri, Giorgio Anselmi, Thibaut Perchet, Jakob Loschko, Juan Dubrot, Rajen Patel, Emmanuel L Gautier, Stéphanie Hugues, M Paula Longhi, Jake Y Henry, Sergio A Quezada, Grégoire Lauvau, Ana-Maria Lennon-Duménil, Enrique Gutiérrez-Martínez, Alain Bessis, Elisa Gomez-Perdiguero, Christian E Jacome-Galarza, Hannah Garner, Frederic Geissmann, Rachel Golub, Michel C Nussenzweig, Pierre Guermonprez
Inflammation triggers the differentiation of Ly6C(hi) monocytes into microbicidal macrophages or monocyte-derived dendritic cells (moDCs). Yet, it is unclear whether environmental inflammatory cues control the polarization of monocytes toward each of these fates or whether specialized monocyte progenitor subsets exist before inflammation. Here, we have shown that naive monocytes are phenotypically heterogeneous and contain an NR4A1- and Flt3L-independent, CCR2-dependent, Flt3(+)CD11c(-)MHCII(+)PU.1(hi) subset...
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/27992436/transcriptomic-analysis-shows-decreased-cortical-expression-of-nr4a1-nr4a2-and-rxrb-in-schizophrenia-and-provides-evidence-for-nuclear-receptor-dysregulation
#9
Susan M Corley, Shan-Yuan Tsai, Marc R Wilkins, Cynthia Shannon Weickert
Many genes are differentially expressed in the cortex of people with schizophrenia, implicating factors that control transcription more generally. Hormone nuclear receptors dimerize to coordinate context-dependent changes in gene expression. We hypothesized that members of two families of nuclear receptors (NR4As), and retinoid receptors (RARs and RXRs), are altered in the dorsal lateral prefrontal cortex (DLPFC) of people with schizophrenia. We used next generation sequencing and then qPCR analysis to test for changes in mRNA levels for transcripts encoding nuclear receptors: orphan nuclear receptors (3 in the NR4A, 3 in the RAR, 3 in the RXR families and KLF4) in total RNA extracted from the DLPFC from people with schizophrenia compared to controls (n = 74)...
2016: PloS One
https://www.readbyqxmd.com/read/27966542/epilepsy-causing-sequence-variations-in-sik1-disrupt-synaptic-activity-response-gene-expression-and-affect-neuronal-morphology
#10
Christoph Pröschel, Jeanne N Hansen, Adil Ali, Emily Tuttle, Michelle Lacagnina, Georgia Buscaglia, Marc W Halterman, Alex R Paciorkowski
SIK1 syndrome is a newly described developmental epilepsy disorder caused by heterozygous mutations in the salt-inducible kinase SIK1. To better understand the pathophysiology of SIK1 syndrome, we studied the effects of SIK1 pathogenic sequence variations in human neurons. Primary human fetal cortical neurons were transfected with a lentiviral vector to overexpress wild-type and mutant SIK1 protein. We evaluated the transcriptional activity of known downstream gene targets in neurons expressing mutant SIK1 compared with wild type...
February 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/27940566/glucose-regulates-the-intrinsic-inflammatory-response-of-the-heart-to-surgically-induced-hypothermic-ischemic-arrest-and-reperfusion
#11
Ahmed S Bux, Merry L Lindsey, Hernan G Vasquez, Heinrich Taegtmeyer, Romain Harmancey
We investigated the isolated working rat heart as a model to study early transcriptional remodeling induced in the setting of open heart surgery and stress hyperglycemia. Hearts of male Sprague Dawley rats were cold-arrested in Krebs-Henseleit buffer and subjected to 60 min normothermic reperfusion in the working mode with buffer supplemented with noncarbohydrate substrates plus glucose (25 mM) or mannitol (25 mM; osmotic control). Gene expression profiles were determined by microarray analysis and compared with those of nonperfused hearts...
January 1, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/27889530/identification-of-proximal-biomarkers-of-pkc-agonism-and-evaluation-of-their-role-in-hiv-reactivation
#12
Sai Vikram Vemula, Jill W Maxwell, Alexey Nefedov, Bang-Lin Wan, Justin Steve, William Newhard, Rosa I Sanchez, David Tellers, Richard J Barnard, Wade Blair, Daria Hazuda, Andrea L Webber, Bonnie J Howell
DESIGN: The HIV latent CD4(+) T cell reservoir is broadly recognized as a barrier to HIV cure. Induction of HIV expression using protein kinase C (PKC) agonists is one approach under investigation for reactivation of latently infected CD4(+) T cells (Beans et al., 2013; Abreu et al., 2014; Jiang et al., 2014; Jiang and Dandekar, 2015). We proposed that an increased understanding of the molecular mechanisms of action of PKC agonists was necessary to inform on biological signaling and pharmacodynamic biomarkers...
November 23, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27876882/nr4a1-knockdown-suppresses-seizure-activity-by-regulating-surface-expression-of-nr2b
#13
Yanke Zhang, Guojun Chen, Baobing Gao, Yunlin Li, Shuli Liang, Xiaofei Wang, Xuefeng Wang, Binglin Zhu
Nuclear receptor subfamily 4 group A member 1 (NR4A1), a downstream target of CREB that is a key regulator of epileptogenesis, has been implicated in a variety of biological processes and was previously identified as a seizure-associated molecule. However, the relationship between NR4A1 and epileptogenesis remains unclear. Here, we showed that NR4A1 protein was predominantly expressed in neurons and up-regulated in patients with epilepsy as well as pilocarpine-induced mouse epileptic models. NR4A1 knockdown by lentivirus transfection (lenti-shNR4A1) alleviated seizure severity and prolonged onset latency in mouse models...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27873103/differential-regulation-of-angiogenic-cellular-processes-and-claudin-5-by-histamine-and-vegf-via-pi3k-signaling-transcription-factor-snai2-and-interleukin-8
#14
Johanna P Laakkonen, Jari P Lappalainen, Thomas L Theelen, Pyry I Toivanen, Tiina Nieminen, Suvi Jauhiainen, Minna U Kaikkonen, Judith C Sluimer, Seppo Ylä-Herttuala
AIMS: Histamine and vascular endothelial growth factor A (VEGF) are central regulators in vascular pathologies. Their gene regulation leading to vascular remodeling has remained obscure. In this study, EC regulation mechanisms of histamine and VEGF were compared by RNA sequencing of primary endothelial cells (ECs), functional in vitro assays and in vivo permeability mice model. METHODS AND RESULTS: By RNA sequencing, similar transcriptional alterations of genes involved in activation of primary ECs, cell proliferation and adhesion were observed between histamine and VEGF...
November 21, 2016: Angiogenesis
https://www.readbyqxmd.com/read/27864345/pax3-foxo1a-expression-in-rhabdomyosarcoma-is-driven-by-the-targetable-nuclear-receptor-nr4a1
#15
Alexandra Lacey, Aline Rodrigues-Hoffman, Stephen Safe
Alveolar rhabdomyosarcoma (ARMS) is a devastating pediatric disease driven by expression of the oncogenic fusion gene PAX3-FOXO1A. In this study, we report overexpression of the nuclear receptor NR4A1 in rhabdomyosarcomas that is sufficient to drive high expression of PAX3-FOXO1A there. RNAi-mediated silencing of NR4A1 decreased expression of PAX3-FOXO1A and its downstream effector genes. Similarly, cell treatment with the NR4A1 small-molecule antagonists 1,1-bis(3-indolyl)-1-(p-hydroxy or p-carbomethoxyphenyl)methane (C-DIM) decreased PAX3-FOXO1A...
February 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/27856455/map3k8-modulates-monocyte-state-and-atherogenesis-in-apoe-mice
#16
Carlos Sanz-Garcia, Ángela Sánchez, Constanza Contreras-Jurado, Carmela Cales, Cristina Barranquero, Marta Muñóz, Ramón Merino, Paula Escudero, Maria-Jesús Sanz, Jesús Osada, Ana Aranda, Susana Alemany
OBJECTIVE: Map3k8 (Cot/Tpl2) activates the MKK1/2-ERK1/2, MAPK pathway downstream from interleukin-1R, tumor necrosis factor-αR, NOD-2R, adiponectinR, and Toll-like receptors. Map3k8 plays a key role in innate and adaptive immunity and influences inflammatory processes by modulating the functions of different cell types. However, its role in atherogenesis remains unknown. In this study, we analyzed the role of this kinase in this pathology. APPROACH AND RESULTS: We show here that Map3k8 deficiency results in smaller numbers of Ly6C(high)CD11c(low) and Ly6C(low)CD11c(high) monocytes in ApoE(-)(/-) mice fed a high-fat diet (HFD)...
November 17, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27814941/deleting-an-nr4a1-super-enhancer-subdomain-ablates-ly6c-low-monocytes-while-preserving-macrophage-gene-function
#17
Graham D Thomas, Richard N Hanna, Neelakatan T Vasudevan, Anouk A Hamers, Casey E Romanoski, Sara McArdle, Kevin D Ross, Amy Blatchley, Deborah Yoakum, Bruce A Hamilton, Zbigniew Mikulski, Mukesh K Jain, Christopher K Glass, Catherine C Hedrick
Mononuclear phagocytes are a heterogeneous family that occupy all tissues and assume numerous roles to support tissue function and systemic homeostasis. Our ability to dissect the roles of individual subsets is limited by a lack of technologies that ablate gene function within specific mononuclear phagocyte sub-populations. Using Nr4a1-dependent Ly6C(low) monocytes, we present a proof-of-principle approach that addresses these limitations. Combining ChIP-seq and molecular approaches we identified a single, conserved, sub-domain within the Nr4a1 enhancer that was essential for Ly6C(low) monocyte development...
November 15, 2016: Immunity
https://www.readbyqxmd.com/read/27814740/spatio-temporal-profile-phenotypic-diversity-and-fate-of-recruited-monocytes-into-the-post-ischemic-brain
#18
Lidia Garcia-Bonilla, Giuseppe Faraco, Jamie Moore, Michelle Murphy, Gianfranco Racchumi, Jayashree Srinivasan, David Brea, Costantino Iadecola, Josef Anrather
BACKGROUND: A key feature of the inflammatory response after cerebral ischemia is the brain infiltration of blood monocytes. There are two main monocyte subsets in the mouse blood: CCR2(+)Ly6C(hi) "inflammatory" monocytes involved in acute inflammation, and CX3CR1(+)Ly6C(lo) "patrolling" monocytes, which may play a role in repair processes. We hypothesized that CCR2(+)Ly6C(hi) inflammatory monocytes are recruited in the early phase after ischemia and transdifferentiate into CX3CR1(+)Ly6C(lo) "repair" macrophages in the brain...
November 4, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27811009/penfluridol-represses-integrin-expression-in-breast-cancer-through-induction-of-reactive-oxygen-species-and-downregulation-of-sp-transcription-factors
#19
Erik Hedrick, Xi Li, Stephen Safe
It was recently demonstrated the penfluridol inhibited breast tumor growth and metastasis and this was associated with downregulation of α6- and β4-integrins. In this study, we observed the penfluridol induced reactive oxygen species (ROS) and this was the primary mechanism of action. Penfluridol-mediated growth inhibition, induction of apoptosis, and inhibition of breast cancer cell migration was attenuated after cotreatment with glutathione. Penfluridol also downregulated Sp transcription factors Sp1, Sp3, and Sp4 through epigenetic downregulation of cMyc and cMyc-regulated miRNAs (miR27a and miR20a/miR17) and induction of the miR-regulated Sp transcriptional repressors ZBTB10 and ZBTB4...
January 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27807832/transcriptome-and-proteome-analyses-of-tnfaip8-knockdown-cancer-cells-reveal-new-insights-into-molecular-determinants-of-cell-survival-and-tumor-progression
#20
Timothy F Day, Rajshree R Mewani, Joshua Starr, Xin Li, Debyani Chakravarty, Habtom Ressom, Xiaojun Zou, Ofer Eidelman, Harvey B Pollard, Meera Srivastava, Usha N Kasid
Tumor necrosis factor-α-inducible protein 8 (TNFAIP8) is the first discovered oncogenic and an anti-apoptotic member of a conserved TNFAIP8 or TIPE family of proteins. TNFAIP8 mRNA is induced by NF-kB, and overexpression of TNFAIP8 has been correlated with poor prognosis in many cancers. Downregulation of TNFAIP8 expression has been associated with decreased pulmonary colonization of human tumor cells, and enhanced sensitivities of tumor xenografts to radiation and docetaxel. Here we have investigated the effects of depletion of TNFAIP8 on the mRNA, microRNA and protein expression profiles in prostate and breast cancers and melanoma...
2017: Methods in Molecular Biology
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