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https://www.readbyqxmd.com/read/29736687/cyclooxygenase-and-lipoxygenase-gene-expression-in-the-inflammogenesis-of-breast-cancer
#1
Brian M Kennedy, Randall E Harris
We examined the expression of major inflammatory genes, cyclooxygenase-1 and 2 (COX1, COX2) and arachidonate 5-lipoxygenase (ALOX5) in 1090 tumor samples of invasive breast cancer from The Cancer Genome Atlas (TCGA). Mean cyclooxygenase expression (COX1 + COX2) ranked in the upper 99th percentile of all 20,531 genes and surprisingly, the mean expression of COX1 was more than tenfold higher than COX2. Highly significant correlations were observed between COX2 with eight tumor-promoting genes (EGR2, IL6, RGS2, B3GNT5, SGK1, SLC2A3, SFRP1 and ETS2) and between ALOX5 and ten tumor promoter genes (CD33, MYOF1, NLRP1, GAB3, CD4, IFR8, CYTH4, BTK, FGR, CD37)...
May 7, 2018: Inflammopharmacology
https://www.readbyqxmd.com/read/29735551/novel-richter-s-syndrome-xenograft-models-to-study-genetic-architecture-biology-and-therapy-responses
#2
Tiziana Vaisitti, Esteban Braggio, John N Allan, Francesca Arruga, Sara Serra, Alberto Zamò, Wayne Tam, Amy Chadburn, Richard R Furman, Silvia Deaglio
Richter's syndrome (RS) represents the evolution of chronic lymphocytic leukemia into an aggressive tumor, most commonly diffuse large B cell lymphoma. The lack of in vitro and in vivo models has severely hampered drug testing in a disease that is poorly responsive to common chemo-immunotherapeutic combinations as well as to novel kinase inhibitors. Here we report for the first time the establishment and genomic characterization of two patient-derived tumor xenograft models of RS, RS9737 and RS1316. RS xenografts were genetically, morphologically and phenotypically stable and similar to the corresponding primary tumor...
May 7, 2018: Cancer Research
https://www.readbyqxmd.com/read/29731343/cell-identity-switching-regulated-by-retinoic-acid-signaling-maintains-homogeneous-segments-in-the-hindbrain
#3
Megan Addison, Qiling Xu, Jordi Cayuso, David G Wilkinson
The patterning of tissues to form subdivisions with distinct and homogeneous regional identity is potentially disrupted by cell intermingling. Transplantation studies suggest that homogeneous segmental identity in the hindbrain is maintained by identity switching of cells that intermingle into another segment. We show that switching occurs during normal development and is mediated by feedback between segment identity and the retinoic acid degrading enzymes, cyp26b1 and cyp26c1. egr2, which specifies the segmental identity of rhombomeres r3 and r5, underlies the lower expression level of cyp26b1 and cyp26c1 in r3 and r5 compared with r2, r4, and r6...
April 30, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29728568/egr2-independent-klf1-mediated-induction-of-pd-l1-in-cd4-t-cells
#4
Shuzo Teruya, Tomohisa Okamura, Toshihiko Komai, Mariko Inoue, Yukiko Iwasaki, Shuji Sumitomo, Hirofumi Shoda, Kazuhiko Yamamoto, Keishi Fujio
Programmed death ligand 1 (PD-L1)-mediated induction of immune tolerance has been vigorously investigated in autoimmunity and anti-tumor immunity. However, details of the mechanism by which PD-L1 is induced in CD4+ T cells are unknown. Here, we revealed the potential function of Klf1 and Egr2-mediated induction of PD-L1 in CD4+ T cells. We focused on the molecules specifically expressed in CD4+ CD25- LAG3+ regulatory T cells (LAG3+ Tregs) highly express of PD-L1 and transcription factor Egr2. Although ectopic expression of Egr2 induced PD-L1, a deficiency of Egr2 did not affect its expression, indicating the involvement of another PD-L1 induction mechanism...
May 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29719630/genetic-susceptibility-to-bone-and-soft-tissue-sarcomas-a-field-synopsis-and-meta-analysis
#5
Clara Benna, Andrea Simioni, Sandro Pasquali, Davide De Boni, Senthilkumar Rajendran, Giovanna Spiro, Chiara Colombo, Calogero Virgone, Steven G DuBois, Alessandro Gronchi, Carlo Riccardo Rossi, Simone Mocellin
Background: The genetic architecture of bone and soft tissue sarcomas susceptibility is yet to be elucidated. We aimed to comprehensively collect and meta-analyze the current knowledge on genetic susceptibility in these rare tumors. Methods: We conducted a systematic review and meta-analysis of the evidence on the association between DNA variation and risk of developing sarcomas through searching PubMed, The Cochrane Library, Scopus and Web of Science databases...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29661920/dhtkd1-deficiency-causes-charcot-marie-tooth-disease-in-mice
#6
Wang-Yang Xu, Houbao Zhu, Yan Shen, Ying-Han Wan, Xiao-Die Tu, Wen-Ting Wu, Lingyun Tang, Hong-Xin Zhang, Shun-Yuan Lu, Xiao-Long Jin, Jian Fei, Zhu-Gang Wang
DHTKD1, a part of 2-ketoadipic acid dehydrogenase complex, is involved in lysine and tryptophan catabolism. Mutations in DHTKD1 block the metabolic pathway and cause 2-aminoadipic and 2-oxoadipic aciduria (AMOXAD), an autosomal recessive inborn metabolic disorder. In addition, a nonsense mutation in DHTKD1 we identified previously causes Charcot-Marie-Tooth disease (CMT) type 2Q, one of the most common inherited neurological disorders affecting the peripheral nerves in the musculature. However, the comprehensive molecular mechanism underlying CMT2Q remains elusive...
April 16, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29656594/immune-imbalance-of-global-gene-expression-and-cytokine-chemokine-and-selectin-levels-in-the-brains-of-offspring-with-social-deficits-via-maternal-immune-activation
#7
Pei-Tan Hsueh, Hsi-Hsun Lin, Hsuan-Han Wang, Chiu-Lin Liu, Wei-Fen Ni, Jong-Kang Liu, Hsin-Hou Chang, Der-Shan Sun, Yao-Shen Chen, Ya-Lei Chen
The murine maternal immune activation (MIA) offspring model enables longitudinal studies to explore aberrant social behaviors similar to those observed in humans. High levels of cytokines, chemokines and cell adhesion molecules (CAM) have been found in the plasma and/or brains of psychiatric patients. We hypothesized that up-regulation of the systemic or brain immune response has an augmenting effect by potentially increasing the interplay between the neuronal and immune systems during the growth of the MIA offspring...
April 15, 2018: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/29580816/overexpression-of-egr2-and-egr4-protects-rat-brains-against-ischemic-stroke-by-downregulating-jnk-signaling-pathway
#8
Rui-Na Niu, Xiao-Ping Shang, Jun-Fang Teng
OBJECTIVE: The purpose of this study was to investigate the effect of Egr2 and Egr4 upregulation on ischemic stroke recovery of rats. METHODS: In this study, Sprague Dawley (SD) rats assigned at random into control, sham and MCAO (middle cerebral artery occlusion) group were treated accordingly to build MCAO models. The neurological severity scores (NSS) test was applied to assess rats' behavior. Triphenyltetrazolium chloride (TTC) staining reflected infarct areas while Nissl staining revealed the number of neurons...
March 23, 2018: Biochimie
https://www.readbyqxmd.com/read/29546053/-positive-regulation-of-rna-metabolic-process-ontology-group-highly-regulated-in-porcine-oocytes-matured-in-vitro-a-microarray-approach
#9
Piotr Celichowski, Mariusz J Nawrocki, Marta Dyszkiewicz-Konwińska, Maurycy Jankowski, Joanna Budna, Artur Bryja, Wiesława Kranc, Sylwia Borys, Sandra Knap, Sylwia Ciesiółka, Michal Jeseta, Karolina Piasecka-Stryczyńska, Ronza Khozmi, Dorota Bukowska, Paweł Antosik, Klaus P Brüssow, Małgorzata Bruska, Michał Nowicki, Maciej Zabel, Bartosz Kempisty
The cumulus-oocyte complexes (COCs) growth and development during folliculogenesis and oogenesis are accompanied by changes involving synthesis and accumulation of large amount of RNA and proteins. In this study, the transcriptomic profile of genes involved in "oocytes RNA synthesis" in relation to in vitro maturation in pigs was investigated for the first time. The RNA was isolated from oocytes before and after in vitro maturation (IVM). Interactions between differentially expressed genes/proteins belonging to "positive regulation of RNA metabolic process" ontology group were investigated by STRING10 software...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29535721/early-growth-response-gene-2-expressing-cd4-lag3-regulatory-t-cells-the-therapeutic-potential-for-treating-autoimmune-diseases
#10
REVIEW
Tomohisa Okamura, Kazuhiko Yamamoto, Keishi Fujio
Regulatory T cells (Tregs) are necessary for the maintenance of immune tolerance. Tregs are divided into two major populations: one is thymus derived and the other develops in the periphery. Among these Tregs, CD4+ CD25+ Tregs, which mainly originate in the thymus, have been extensively studied. Transcription factor Foxp3 is well known as a master regulatory gene for the development and function of CD4+ CD25+ Tregs. On the other hand, peripheral Tregs consist of distinct cell subsets including Foxp3-dependent extrathymically developed Tregs and interleukin (IL)-10-producing type I regulatory T (Tr1) cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29491350/egr2-dependent-microrna-138-is-dispensable-for-peripheral-nerve-myelination
#11
Hsin-Pin Lin, Idil Oksuz, John Svaren, Rajeshwar Awatramani
Recent studies have elucidated the crucial role for microRNAs in peripheral nerve myelination by ablating components of the microRNA synthesis machinery. Few studies have focused on the role of individual microRNAs. To fill this gap, we focused this study on miR-138, which was shown to be drastically reduced in Dicer1 and Dgcr8 knockout mice with hypomyelinating phenotypes and to potentially target the negative regulators of Schwann cell differentiation. Here, we show that of two miR-138 encoding loci, mir-138-1 is the predominant locus transcribed in Schwann cells...
February 28, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29375712/microrna-20a-promotes-proliferation-and-invasion-by-directly-targeting-early-growth-response-2-in-non-small-cell-lung-carcinoma
#12
Lai Wei, Fengming Ran
MicroRNA-20a (miR-20a) serves a notable role in tumor development and progression; it functions differently in different types of malignant tumor, and its role and mechanism in non-small cell lung carcinoma (NSCLC) remains unclear. In the present study, the effects of miR-20a on the proliferation and invasion of NSCLC cells and the underlying mechanisms behind this were investigated. Reverse transcription-quantitative polymerase chain reaction revealed that the expression level of miR-20a was higher in human NSCLC than in normal tissues...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29339557/chronic-dietary-creatine-enhances-hippocampal-dependent-spatial-memory-bioenergetics-and-levels-of-plasticity-related-proteins-associated-with-nf-%C3%AE%C2%BAb
#13
Wanda M Snow, Chris Cadonic, Claudia Cortes-Perez, Subir K Roy Chowdhury, Jelena Djordjevic, Ella Thomson, Michael J Bernstein, Miyoung Suh, Paul Fernyhough, Benedict C Albensi
The brain has a high demand for energy, of which creatine (Cr) is an important regulator. Studies document neurocognitive benefits of oral Cr in mammals, yet little is known regarding their physiological basis. This study investigated the effects of Cr supplementation (3%, w/w) on hippocampal function in male C57BL/6 mice, including spatial learning and memory in the Morris water maze and oxygen consumption rates from isolated mitochondria in real time. Levels of transcription factors and related proteins (CREB, Egr1, and IκB to indicate NF-κB activity), proteins implicated in cognition (CaMKII, PSD-95, and Egr2), and mitochondrial proteins (electron transport chain Complex I, mitochondrial fission protein Drp1) were probed with Western blotting...
February 2018: Learning & Memory
https://www.readbyqxmd.com/read/29336362/screening-for-sh3tc2-pmp2-and-bscl2-variants-in-a-cohort-of-chinese-patients-with-charcot-marie-tooth
#14
Xin Zhao, Ming-Ming Jiang, Yi-Zhou Yan, Lei Liu, Yong-Zhi Xie, Xiao-Bo Li, Zheng-Mao Hu, Xiao-Hong Zi, Kun Xia, Bei-Sha Tang, Ru-Xu Zhang
BACKGROUND: SH3TC2, PMP2, and BSCL2 genes are related to autosomal recessive (AR) Charcot-Marie-Tooth (CMT) disease type 1, autosomal dominant (AD)-CMT1, and AD-CMT2, respectively. Pathogenic variants in these three genes were not well documented in Chinese CMT patients. Therefore, this study aims to detect SH3TC2, PMP2, and BSCL2 pathogenic variants in a cohort of 315 unrelated Chinese CMT families. METHODS: A total of 315 probands from 315 unrelated Chinese CMT families were recruited from the Department of Neurology of Third Xiangya Hospital and Xiangya Hospital...
January 20, 2018: Chinese Medical Journal
https://www.readbyqxmd.com/read/29314730/transcription-factors-early-growth-response-gene-egr-2-and-3-control-inflammatory-responses-of-tolerant-t-cells
#15
Becky Omodho, Tizong Miao, Alistair L J Symonds, Randeep Singh, Suling Li, Ping Wang
INTRODUCTION: Impaired proliferation and production of IL2 are the hallmarks of experimental T cell tolerance. However, in most autoimmune diseases, auto-reactive T cells do not display hyper proliferation, but inflammatory phenotypes. METHODS: We have now demonstrated that the transcription factors Egr2 and 3 are important for the control of inflammatory cytokine production by tolerant T cells, but not for tolerance induction. RESULTS: In the absence of Egr2 and 3, T cell tolerance, as measured by impaired proliferation and production of IL2, can still be induced, but tolerant T cells produced high levels of inflammatory cytokines...
January 3, 2018: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/29198014/inhibition-of-complement-drives-increase-in-early-growth-response-proteins-and-neuroprotection-mediated-by-salidroside-after-cerebral-ischemia
#16
Wenfang Lai, XiuLi Xie, Xiaoqin Zhang, Yingzheng Wang, Kedan Chu, John Brown, Lidian Chen, Guizhu Hong
Salidroside is neuroprotective across a wide therapeutic time-window after cerebral ischemia-reperfusion injury (IRI). Here, we investigated the role of complement in mediating effects of salidroside after cerebral IRI in rats. Rats were administrated with vehicle or salidroside 50 mg/kg, given daily for either 24 or 48 h, after middle cerebral artery occlusion (MCAO) for 2 h and reperfusion for 1 h. Levels of proteins in ischemic brain were measured by immunofluorescence and western blotting. We observed early increases in the deposition of immunoglobulin M, mannose-binding lectin 2, and annexin IV on cerebral endothelial cells, induction of the complement components C3 and C3a, by 24 h after IRI, and a later significant increase in the complement component C1q by 48 h...
December 2, 2017: Inflammation
https://www.readbyqxmd.com/read/29174527/genotypic-and-phenotypic-spectrum-of-the-most-common-causative-genes-of-charcot-marie-tooth-disease-in-hungarian-patients
#17
György Máté Milley, Edina Timea Varga, Zoltán Grosz, Csilla Nemes, Zsuzsanna Arányi, Judit Boczán, Péter Diószeghy, Mária Judit Molnár, Anikó Gál
Charcot-Marie-Tooth neuropathy (CMT) is a genetically and clinically heterogeneous group of neuromuscular disorders with an overall prevalence of 1 per 2500. Here we report the first comprehensive genetic epidemiology study of Hungarian CMT patients. 409 CMT1 and 122 CMT2 patients were enrolled and genetic testing of PMP22, GJB1, MPZ, EGR2 and MFN2 genes were performed routinely. NDRG1 and CTDP1 genes were screened only for founder mutations in Roma patients. Causative genetic mutations were identified in 67...
January 2018: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/29156711/multiple-regulatory-aspects-of-histone-methyltransferase-ezh2-in-pb-induced-neurotoxicity
#18
Wei-Zhen Xue, Xiaozhen Gu, Yulan Wu, Danyang Li, Yi Xu, Hui-Li Wang
Pb is a pervasive environmental threat to human health. Although remarkable progress has been made in its neurotoxicity, the precise molecular mechanisms underlying this widespread toxicant still remain elusive. In this study, the detailed roles of EZH2, a transcriptional repressor, in the regulation of Pb-led neurotoxicity were investigated, highlighting its sub-functionalization, compartmentalization, functional chaperones and downstream partners. Based on the findings, EZH2's protein levels were significantly reduced in response to Pb treatment; EZH2's gain-of-function trials recovered the dampened neurite outgrowth; EZH2' recruitment to ploycomb complex, as well as its interaction with cytosolic Vav1, was altered in a distinct manner, suggesting that EZH2's multiple roles were markedly redistributed in this context; EZH2's cytosolic and nuclear presence differed in their respective response towards Pb treatment; EZH2 directly occupied the promoters of EGR2 , NGFR and CaMKK2 , genes responsible for various nerve functions and repair mechanisms, and essentially contributed to their aberrant expression...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29153954/mir-150-5p-regulates-egr2-to-promote-the-development-of-chronic-rhinosinusitis-via-the-dc-th-axis
#19
Zuxia Ma, Yang Shen, Quan Zeng, Jie Liu, Li Yang, Ran Fu, Guohua Hu
BACKGROUND AND AIMS: Accumulating studies indicate that miR-150-5p might play a significant role in dendritic cells (DCs) of peripheral blood in chronic rhinosinusitis (CRS) patients. We sought to investigate the effects and mechanism of miR-150-5p, which regulates early growth response 2 (EGR2) to promote the development of CRS via the DC-Th axis. METHODS: The upregulated expression of miR-150-5p in DCs of CRS was assayed by real-time quantitative polymerase chain reaction (qRT-PCR), and IL-17 cytokines in the supernatants of DC-naïve T cells co-cultures were analysed by enzyme-linked immunosorbent assay (ELISA)...
January 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29152100/differential-regulation-of-mrnas-and-lncrnas-related-to-lipid-metabolism-in-two-pig-breeds
#20
Wanlong Huang, Xiuxiu Zhang, Ai Li, Lingli Xie, Xiangyang Miao
Long non-coding RNAs (lncRNAs) can regulate lipid metabolism and adipogenesis. However, there is little research on the role of lncRNAs in fat deposition in pig. In this study, RNA-seq technology was used to analyze the gene expression profiles of subcutaneous adipose tissue in Laiwu (LW) and Large White (LY) pigs. Then, key lncRNAs and genes associated with lipid metabolism and adipogenic differentiation were identified. Fifty four lncRNAs and 482 known mRNAs were differentially expressed in the two pig breeds...
October 20, 2017: Oncotarget
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