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https://www.readbyqxmd.com/read/28323970/obesity-modulates-inflammation-and-lipid-metabolism-oocyte-gene-expression-a-single-cell-transcriptome-perspective
#1
Meghan L Ruebel, Matthew Cotter, Clark R Sims, Dean M Moutos, Thomas M Badger, Mario A Cleves, Kartik Shankar, Aline Andres
Context: It is hypothesized that obesity adversely affects the ovarian environment which can disrupt oocyte maturation and may further impact embryonic development. Objective: This study aimed to compare oocyte gene expression profiles and follicular fluid (FF) content from overweight/obese (OW) women and normal weight (NW) women who were undergoing fertility treatments. Design: Using single cell transcriptomic analyses, we investigated oocyte gene expression using RNA-seq...
March 15, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28319094/targeting-c-fos-and-dusp1-abrogates-intrinsic-resistance-to-tyrosine-kinase-inhibitor-therapy-in-bcr-abl-induced-leukemia
#2
Meenu Kesarwani, Zachary Kincaid, Ahmed Gomaa, Erika Huber, Sara Rohrabaugh, Zain Siddiqui, Muhammad F Bouso, Tahir Latif, Ming Xu, Kakajan Komurov, James C Mulloy, Jose A Cancelas, H Leighton Grimes, Mohammad Azam
Tyrosine-kinase inhibitor (TKI) therapy for human cancers is not curative, and relapse occurs owing to the continued presence of tumor cells, referred to as minimal residual disease (MRD). The survival of MRD stem or progenitor cells in the absence of oncogenic kinase signaling, a phenomenon referred to as intrinsic resistance, depends on diverse growth factors. Here we report that oncogenic kinase and growth-factor signaling converge to induce the expression of the signaling proteins FBJ osteosarcoma oncogene (c-FOS, encoded by Fos) and dual-specificity phosphatase 1 (DUSP1)...
March 20, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28283576/glucocorticoid-and-cytokine-crosstalk-feedback-feedforward-and-co-regulatory-interactions-determine-repression-or-resistance
#3
Robert Newton, Suharsh V Shah, Mohammed O Altonsy, Anthony N Gerber
Inflammatory signals induce complex feedback and feedforward systems that allow tight temporal control. Whereas glucocorticoids generally repress inflammatory gene expression, GR recruitment increases expression of negative feedback and feedforward regulators, including DUSP1, IRAK3, NFKBIA, TNFAIP3 or ZFP36. Moreover, GR cooperativity with factors, such as NF-κB, can enhance regulator expression to promote repression. Conversely, MAPKs, which are inhibited by glucocorticoids, limit expression of the transcription factor IRF1, and the host defense gene, CXCL10, through a feedforward control mechanism...
March 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28283554/impaired-dual-specificity-protein-phosphatase-dusp4-reduces-corticosteroid-sensitivity
#4
Yoshiki Kobayashi, Kazuhiro Ito, Akira Kanda, Koich Tomoda, Nicolas Mercado, Peter Barnes
We have reported that phosphorylation of glucocorticoid receptor (GR) at Ser(226) reduces GR nuclear translocation resulting in corticosteroid insensitivity in patients with severe asthmas. A serine/threonine protein phosphatase, PP2A, which regulates JNK1 and GR-Ser(226) signaling, is involved in this mechanism. Here, we further explored dual-specificity protein kinases (DUSPs) with the ability to dephosphorylate JNK, and identified DUSP4 as a phosphatase involved in the regulation of corticosteroid sensitivity...
March 10, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28257662/daucane-esters-from-laserwort-laserpitium-latifolium-l-inhibit-cytokine-and-chemokine-production-in-human-lung-epithelial-cells
#5
Višnja Popović, Jan Goeman, Jonathan Thommis, Arne Heyerick, Jurgen Caroen, Johan Van der Eycken, Karolien De Bosscher
BACKGROUND: Laserwort, Laserpitium latifolium L. (Apiaceae), is a European medicinal plant. Its roots and rhizomes were traditionally used as a general tonic and to treat inflammatory and infective diseases. PURPOSE: The anti-inflammatory potential of daucane esters, isolated from underground parts extract of L. latifolium and specific structural features that contribute to their activity were investigated. In addition, we studied their interference with the transactivation capacity of the Glucocorticoid Receptor when added together with a classic glucocorticoid (GC), dexamethasone (DEX)...
March 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28220843/dusp1-promoter-methylation-in-peripheral-blood-leukocyte-is-associated-with-triple-negative-breast-cancer-risk
#6
Jing Li, Yanbo Chen, Hongyuan Yu, Jingshen Tian, Fengshun Yuan, Jialong Fan, Yupeng Liu, Lin Zhu, Fan Wang, Yashuang Zhao, Da Pang
DNA methylation is one of the most common epigenetic alterations, providing important information regarding cancer risk and prognosis. A case-control study (423 breast cancer cases, 509 controls) and a case-only study (326 cases) were conducted to evaluate the association of DUSP1 promoter methylation with breast cancer risk and clinicopathological characteristics. No significant association between DUSP1 methylation in peripheral blood leukocyte (PBL) DNA and breast cancer risk was observed. DUSP1 methylation was significantly associated with ER/PR-negative status; in particular, triple-negative breast cancer patients showed the highest frequency of DUSP1 methylation in both tumour DNA and PBL DNA...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28161506/mathematical-modelling-unveils-the-essential-role-of-cellular-phosphatases-in-the-inhibition-of-raf-mek-erk-signalling-by-sorafenib-in-hepatocellular-carcinoma-cells
#7
Zuzana Saidak, Anne-Sophie Giacobbi, Christophe Louandre, Chloé Sauzay, Youcef Mammeri, Antoine Galmiche
The RAS-RAF-MEK-ERK cascade is a key oncogenic signal transduction pathway activated in many types of tumours in humans. Sorafenib, the medical treatment of reference against advanced stages of hepatocellular carcinoma (HCC), inhibits the RAF-MEK-ERK cascade in HCC cells. Based on previous studies suggesting that this cascade is an important target of sorafenib in HCC cells, we explored its regulation using mathematical modelling and ordinary differential equations. We analysed the dynamic regulation of the core components of the RAF-MEK-ERK cascade in three human HCC cell lines (Huh7, Hep3B and PLC/PRF5) with heterogeneous responses to sorafenib...
February 2, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28154014/a-tumor-cell-selective-inhibitor-of-mitogen-activated-protein-kinase-phosphatases-sensitizes-breast-cancer-cells-to-lymphokine-activated-killer-cell-activity
#8
Christof T Kaltenmeier, Laura L Vollmer, Lawrence A Vernetti, Lindsay Caprio, Keanu Davis, Vasiliy N Korotchenko, Billy W Day, Michael Tsang, Keren I Hulkower, Michael T Lotze, Andreas Vogt
Dual specificity mitogen activated protein kinase (MAPK) phosphatases (DUSP-MKPs) have been hypothesized to maintain cancer cell survival by buffering excessive MAPK signaling caused by upstream activating oncogenic products. A large and diverse body of literature suggests that genetic depletion of DUSP-MKPs can reduce tumorigenicity, suggesting that hyperactivating MAPK signaling by DUSP-MKP inhibitors could be a novel strategy to selectively affect the transformed phenotype. Through in vivo structure activity relationship studies in transgenic zebrafish we recently identified a hyperactivator of Fibroblast Growth Factor signaling (BCI-215) that is devoid of developmental toxicity and restores defective MAPK activity caused by overexpression of DUSP1 and DUSP6 in mammalian cells...
February 2, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28129656/dusp1-inhibits-cell-proliferation-metastasis-and-invasion-and-angiogenesis-in-gallbladder-cancer
#9
Jiliang Shen, Senjun Zhou, Liang Shi, Xiaolong Liu, Hui Lin, Hong Yu, Xiaoliang, Jiacheng Tang, Tunan Yu, Xiujun Cai
DUSP1/MKP1 is a dual-specific phosphatase that regulates MAPK activity and is known to play a key role in tumor biology. Its function in gallbladder cancer (GBC) remains largely unknown, however. By exploring its activities in two GBC cell lines (SGC996 and GBC-SD), DUSP1 was found to inhibit GBC cell proliferation, migration and invasion. Moreover, DUSP1 inhibited GBC growth and metastasis in nude mice subcutaneously xenografted with SGC996 cells. The tumor suppression appeared to be mediated via the DUSP1-pERK/MAPK-MMP2 signal pathway...
January 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28125615/a-screen-for-key-genes-and-pathways-involved-in-high-quality-brush-hair-in-the-yangtze-river-delta-white-goat
#10
Haiyan Guo, Guohu Cheng, Yongjun Li, Hao Zhang, Kangle Qin
The Yangtze River Delta White Goat is the only goat breed that produces high-quality brush hair, or type III hair, which is specialized for use in top-grade writing brushes. There has been little research, especially molecular research, on the traits that result in high-quality brush hair in the Yangtze River Delta White Goat. To explore the molecular mechanisms of the formation of high-quality brush hair, High-throughput RNA-Seq technology was used to compare skin samples from Yangtze River Delta White Goats that produce high-quality hair and non high-quality hair for identification of the important genes and related pathways that might influence the hair quality traits...
2017: PloS One
https://www.readbyqxmd.com/read/28120235/identifying-key-genes-associated-with-hirschsprung-s-disease-based-on-bioinformatics-analysis-of-rna-sequencing-data
#11
Wei-Kang Pan, Ya-Fei Zhang, Hui Yu, Ya Gao, Bai-Jun Zheng, Peng Li, Chong Xie, Xin Ge
BACKGROUND: Hirschsprung's disease (HSCR) is a type of megacolon induced by deficiency or dysfunction of ganglion cells in the distal intestine and is associated with developmental disorders of the enteric nervous system. To explore the mechanisms of HSCR, we analyzed the RNA-sequencing data of the expansion and the narrow segments of colon tissues separated from children with HSCR. METHODS: RNA-sequencing of the expansion segments and the narrow segments of colon tissues isolated from children with HSCR was performed...
January 25, 2017: World Journal of Pediatrics: WJP
https://www.readbyqxmd.com/read/28116096/an-inhaled-dose-of-budesonide-induces-genes-involved-in-transcription-and-signaling-in-the-human-airways-enhancement-of-anti-and-proinflammatory-effector-genes
#12
Richard Leigh, Mahmoud M Mostafa, Elizabeth M King, Christopher F Rider, Suharsh Shah, Curtis Dumonceaux, Suzanne L Traves, Andrew McWhae, Tyler Kolisnik, Cora Kooi, Donna M Slater, Margaret M Kelly, Mark Bieda, Anna Miller-Larsson, Robert Newton
Although inhaled glucocorticoids, or corticosteroids (ICS), are generally effective in asthma, understanding their anti-inflammatory actions in vivo remains incomplete. To characterize glucocorticoid-induced modulation of gene expression in the human airways, we performed a randomized placebo-controlled crossover study in healthy male volunteers. Six hours after placebo or budesonide inhalation, whole blood, bronchial brushings, and endobronchial biopsies were collected. Microarray analysis of biopsy RNA, using stringent (≥2-fold, 5% false discovery rate) or less stringent (≥1...
August 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28112450/mapk-pathways-regulation-by-dusp1-in-the-development-of-osteosarcoma-potential-markers-and-therapeutic-targets
#13
Ljs Lopes, F Tesser-Gamba, A S Petrilli, Mts Alves, R J Garcia-Filho, Src Toledo
Osteosarcoma (OS) is the most frequent primary bone tumor that affect children and adolescents. This tumor is highly aggressive with high risk of metastasis and the implementation of new drugs has not been successful. The search for biomarkers or new therapeutic targets is urgently needed and can help in advances of OS treatment. MAPKs are major signaling transduction molecules that play an important role in regulating a variety of cellular responses. DUSP1 is a phosphatase that dephosphorylates the MAPKs. Both MAPKs and DUSPs have been implicated as major modulators of critical signaling pathways that are dysregulated in various diseases...
January 23, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28013190/mycobacterium-indicus-pranii-mw-mediated-protection-against-visceral-leishmaniasis-by-reciprocal-regulation-of-host-dual-specificity-phosphatases
#14
Shabina Parveen, Syamdas Bandhyopadhyay, Sonali Das, Suchandra Bhattacharyya Majumdar, Junaid Jibran Jawed, Bidisha Paul Chowdhury, Bhaskar Saha, Subrata Majumdar
Leishmania donovani resides within the host macrophages by dampening host defence mechanisms and thereby it modulates the host cell functions for its survival. Multiple host cell factors compete during the interplay between the host and the parasite. Roles for dual-specificity phosphatases (DUSPs) are implicated in various pathological conditions. However, the reciprocity of these DUSPs was unknown in L. donovani infection in a susceptible model. Here, we show that Mycobacterium indicus pranii (Mw), an immunomodulator, reciprocally regulates DUSP1 and DUSP6 through the TLR4 pathway...
December 2016: International Immunology
https://www.readbyqxmd.com/read/28004803/convergent-evidence-for-the-molecular-basis-of-musical-traits
#15
Jaana Oikkonen, Päivi Onkamo, Irma Järvelä, Chakravarthi Kanduri
To obtain aggregate evidence for the molecular basis of musical abilities and the effects of music, we integrated gene-level data from 105 published studies across multiple species including humans, songbirds and several other animals and used a convergent evidence method to prioritize the top candidate genes. Several of the identified top candidate genes like EGR1, FOS, ARC, BDNF and DUSP1 are known to be activity-dependent immediate early genes that respond to sensory and motor stimuli in the brain. Several other top candidate genes like MAPK10, SNCA, ARHGAP24, TET2, UBE2D3, FAM13A and NUDT9 are located on chromosome 4q21-q24, on the candidate genomic region for music abilities in humans...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27965980/in-vitro-protective-effects-of-lycium-barbarum-berries-cultivated-in-umbria-italy-on-human-hepatocellular-carcinoma-cells
#16
M R Ceccarini, S Vannini, S Cataldi, M Moretti, M Villarini, B Fioretti, E Albi, T Beccari, M Codini
Lycium barbarum is a famous plant in the traditional Chinese medicine. The plant is known to have health-promoting bioactive components. The properties of Lycium barbarum berries cultivated in Umbria (Italy) and their effect on human hepatocellular carcinoma cells (HepG2) have been investigated in this work. The obtained results demonstrated that the Lycium barbarum berries from Umbria region display high antioxidant properties evaluated by total phenolic content and ORAC method, on hydrophilic and lipophilic fractions...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27849045/deletion-of-neurotrophin-signaling-through-the-glucocorticoid-receptor-pathway-causes-tau-neuropathology
#17
Margarita Arango-Lievano, Camille Peguet, Matthias Catteau, Marie-Laure Parmentier, Synphen Wu, Moses V Chao, Stephen D Ginsberg, Freddy Jeanneteau
Glucocorticoid resistance is a risk factor for Alzheimer's disease (AD). Molecular and cellular mechanisms of glucocorticoid resistance in the brain have remained unknown and are potential therapeutic targets. Phosphorylation of glucocorticoid receptors (GR) by brain-derived neurotrophic factor (BDNF) signaling integrates both pathways for remodeling synaptic structure and plasticity. The goal of this study is to test the role of the BDNF-dependent pathway on glucocorticoid signaling in a mouse model of glucocorticoid resistance...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27795299/beta-interferon-production-is-regulated-by-p38-mitogen-activated-protein-kinase-in-macrophages-via-both-msk1-2-and-tristetraprolin-dependent-pathways
#18
Victoria A McGuire, Dalya Rosner, Olga Ananieva, Ewan A Ross, Suzanne E Elcombe, Shaista Naqvi, Mirjam M W van den Bosch, Claire E Monk, Tamara Ruiz-Zorrilla Diez, Andrew R Clark, J Simon C Arthur
Autocrine or paracrine signaling by beta interferon (IFN-β) is essential for many of the responses of macrophages to pathogen-associated molecular patterns. This feedback loop contributes to pathological responses to infectious agents and is therefore tightly regulated. We demonstrate here that macrophage expression of IFN-β is negatively regulated by mitogen- and stress-activated kinases 1 and 2 (MSK1/2). Lipopolysaccharide (LPS)-induced expression of IFN-β was elevated in both MSK1/2 knockout mice and macrophages...
January 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27706699/increased-mir-155-5p-expression-in-dermal-mesenchymal-stem-cells-of-psoriatic-patients-comparing-the-microrna-expression-profile-by-microarray
#19
R X Hou, R F Liu, X C Zhao, Y R Jia, P An, Z P Hao, J Q Li, X H Li, G H Yin, K M Zhang
Mesenchymal stem cells (MSCs) have pleiotropic immuno-modulatory effects and pro-angiogenic ability, leading to the presumption that MSCs may be involved in the pathogenesis of many inflammatory or autoimmune disorders, including psoriasis. In a previous study, we reported the specific gene expression profile of dermal MSCs from psoriasis. Inflammation- and angiogenesis-related genes, such as lipopolysaccharide-induced tumor necrosis factor-alpha transcription factor (LITAF), dual-specificity protein phosphatase 1 (DUSP1), vascular endothelial growth factor α (VEGFα), and insulin-like growth factor-binding protein-5 (IGFBP5), are abnormally expressed in psoriatic dermal MSCs...
September 2, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27682256/impact-of-heat-stress-on-cellular-and-transcriptional-adaptation-of-mammary-epithelial-cells-in-riverine-buffalo-bubalus-bubalis
#20
Neha Kapila, Ankita Sharma, Amit Kishore, Monika Sodhi, Pawan K Tripathi, Ashok K Mohanty, Manishi Mukesh
The present study aims to identify the heat responsive genes and biological pathways in heat stressed buffalo mammary epithelial cells (MECs). The primary mammary epithelial cells of riverine buffalo were exposed to thermal stress at 42°C for one hour. The cells were subsequently allowed to recover at 37°C and harvested at different time intervals (30 min to 48 h) along with control samples (un-stressed). In order to assess the impact of heat stress in buffalo MECs, several in-vitro cellular parameters (lactate dehydrogenase activity, cell proliferation assay, cellular viability, cell death and apoptosis) and transcriptional studies were conducted...
2016: PloS One
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