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Ben X Wang, Stephanie A Grover, Peter Kannu, Grace Yoon, Ronald M Laxer, E Ann Yeh, Eleanor N Fish
Aicardi-Goutières syndrome (AGS) is an early-onset, genetic disease characterized by recurrent fever, multifocal lesions of the brain, and systemic autoimmunity. We report on 3 AGS patients, 2 siblings with an RNASEH2A gene mutation and 1 patient with a SAMHD1 gene mutation. Serial analysis of peripheral blood from all 3 AGS patients showed consistently elevated expression of the interferon-stimulated genes (ISGs): ISG15, RSAD2, and IFI27, not observed in unaffected family members. Enumeration of circulating white blood cells and platelets and examination of C-reactive protein showed no significant deviation from the normal range for Patient 2 with the RNASEH2A mutation and Patient 3 with the SAMHD1 mutation, even when Patient 2 had magnetic resonance imaging abnormalities and ongoing febrile episodes...
April 2017: Journal of Interferon & Cytokine Research
Guang Li, Xian Li, Meng Yang, Lvzi Xu, Shixiong Deng, Longke Ran
Microarray data is used to screen the genes of oral squamous cell carcinoma (OSCC). Microarray data of OSCC and normal tissues were downloaded from GEO database and analyzed with Benjamini-Hochberg (BH) method. Differentially expressed genes (DEGs) were then uploaded on DAVID database to process enrichment analysis. Target genes were finally chosen for verification experiment in vitro and in vivo. 78 DEGs were selected from 54676 genes, including 46 up- and 32 down- regulation. GO term showed that these genes were related to epidermal growth (biological processes), extracellular region (cellular components) and cytokines activity (molecular function)...
February 8, 2017: Scientific Reports
Eric A Ariazi, John C Taylor, Michael A Black, Emmanuelle Nicolas, Michael J Slifker, Diana J Azzam, Jeff Boyd
Resistance to hormonal therapies is a major clinical problem in the treatment of estrogen receptor α-positive (ERα(+)) breast cancers. Epigenetic marks, namely DNA methylation of cytosine at specific CpG sites (5mCpG), are frequently associated with ERα(+) status in human breast cancers. Therefore, ERα may regulate gene expression in part via DNA methylation. This hypothesis was evaluated using a panel of breast cancer cell line models of antiestrogen resistance. Microarray gene expression profiling was used to identify genes normally silenced in ERα(+) cells but derepressed upon exposure to the demethylating agent decitabine, derepressed upon long-term loss of ERα expression, and resuppressed by gain of ERα activity/expression...
February 2017: Molecular Cancer Research: MCR
Linda Boldrup, Xiaolian Gu, Philip J Coates, Lena Norberg-Spaak, Robin Fahraeus, Göran Laurell, Torben Wilms, Karin Nylander
Due to the high frequency of loco-regional recurrences, which could be explained by changes in the field surrounding the tumor, patients with squamous cell carcinoma of head and neck show poor survival. Here we identified a total of 554 genes as dysregulated in clinically tumor free tongue tissue in patients with tongue tumors when compared to healthy control tongue tissue. Among the top dysregulated genes when comparing control and tumor free tissue were those involved in apoptosis (CIDEC, MUC1, ZBTB16, PRNP, ECT2), immune response (IFI27) and differentiation (KRT36)...
March 21, 2017: Oncotarget
Rebecca Mahony, Siobhán Gargan, Kim L Roberts, Nollaig Bourke, Sinead E Keating, Andrew G Bowie, Cliona O'Farrelly, Nigel J Stevenson
The cytokine, Interferon (IFN)-α, induces a wide spectrum of anti-viral mediators, via the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. STAT1 and STAT2 are well characterised to upregulate IFN-stimulated gene (ISG) expression; but even though STAT3 is also activated by IFN-α, its role in anti-viral ISG induction is unclear. Several viruses, including Hepatitis C and Mumps, reduce cellular STAT3 protein levels, via the promotion of ubiquitin-mediated proteasomal degradation...
December 17, 2016: Cellular and Molecular Life Sciences: CMLS
Marcia W Carneiro, Kiyoshi F Fukutani, Bruno B Andrade, Rebecca P Curvelo, Juqueline R Cristal, Augusto M Carvalho, Aldina Barral, Johan Van Weyenbergh, Manoel Barral-Netto, Camila I de Oliveira
BACKGROUND: The initial response to Leishmania parasites is essential in determining disease development or resistance. In vitro, a divergent response to Leishmania, characterized by high or low IFN-γ production has been described as a potential tool to predict both vaccine response and disease susceptibility in vivo. METHODS AND FINDINGS: We identified uninfected and healthy individuals that were shown to be either high- or low IFN-γ producers (HPs and LPs, respectively) following stimulation of peripheral blood cells with Leishmania braziliensis...
November 2016: PLoS Neglected Tropical Diseases
Jacqueline U McDonald, Myrsini Kaforou, Simon Clare, Christine Hale, Maria Ivanova, Derek Huntley, Marcus Dorner, Victoria J Wright, Michael Levin, Federico Martinon-Torres, Jethro A Herberg, John S Tregoning
Greater understanding of the functions of host gene products in response to infection is required. While many of these genes enable pathogen clearance, some enhance pathogen growth or contribute to disease symptoms. Many studies have profiled transcriptomic and proteomic responses to infection, generating large data sets, but selecting targets for further study is challenging. Here we propose a novel data-mining approach combining multiple heterogeneous data sets to prioritize genes for further study by using respiratory syncytial virus (RSV) infection as a model pathogen with a significant health care impact...
May 2016: MSystems
Qi-Dong Ye, Hui Jiang, Xue-Lian Liao, Kai Chen, Shan-Shan Li
In the present study, we sought to define genes associated with immune thrombocytopenia (ITP). Microarray analysis revealed that of 1002 genes associated with ITP, 309 genes had downregulated expression and 693 genes had upregulated expression in patients with ITP. Gene set enrichment analysis revealed that 11 pathways were positively correlated to ITP, such as type I diabetes mellitus, intestinal immune network for IgA production, and oxidative phosphorylation. The messenger RNA expression levels of the indicated genes, including HLA-DRB5, IGHV3-66, IFI27, FAM212A, PLD5, tumor necrosis factor (TNF)-α, interferon-γ, interleukin (IL)-1β, and IL-4, were significantly increased in patients with ITP compared with healthy humans, while MMP8, SLC1A3, CRISP3, THBS1, FMN1, and IL-10 were decreased...
August 23, 2016: Journal of Biomolecular Screening
Antonio Salas, Guillermo Marco-Puche, Juan Carlos Triviño, Alberto Gómez-Carballa, Miriam Cebey-López, Irene Rivero-Calle, Lucía Vilanova-Trillo, Carmen Rodríguez-Tenreiro, José Gómez-Rial, Federico Martinón-Torres
The mechanisms of rotavirus (RV) infection have been analyzed from different angles but the way in which RV modifies the transcriptome of the host is still unknown. Whole transcriptome shotgun sequencing of peripheral blood samples was used to reveal patterns of expression from the genome of RV-infected patients. RV provokes global changes in the transcriptome of infected cells, involving an over-expression of genes involved in cell cycle and chromatin condensation. While interferon IFI27 was hyper-activated, interferon type II was not suggesting that RV has developed mechanisms to evade the innate response by host cells after virus infection...
October 2016: Infection, Genetics and Evolution
Peng-Fei Bing, Wei Xia, Lan Wang, Yong-Hong Zhang, Shu-Feng Lei, Fei-Yan Deng
OBJECTIVE: Systemic lupus erythematosus (SLE) is a complex auto-immune disease. Gene expression studies have been conducted to identify SLE-related genes in various types of samples. It is unknown whether there are common marker genes significant for SLE but independent of sample types, which may have potentials for follow-up translational research. The aim of this study is to identify common marker genes across various sample types for SLE. METHODS: Based on four public microarray gene expression datasets for SLE covering three representative types of blood-born samples (monocyte; peripheral blood mononuclear cell, PBMC; whole blood), we utilized three statistics (fold-change, FC; t-test p value; false discovery rate adjusted p value) to scrutinize genes simultaneously regulated with SLE across various sample types...
2016: PloS One
Shikha Shrivastava, Eric G Meissner, Emily Funk, Seerat Poonia, Virender Shokeen, Arun Thakur, Bhawna Poonia, Shiv Kumar Sarin, Nirupma Trehanpati, Shyamasundaran Kottilil
BACKGROUND AND AIMS: HCV GT-3 has a more pronounced effect on hepatic steatosis and host lipids than other HCV genotypes and is proving less responsive to all oral interferon-free treatment with direct acting antiviral agents. As both HCV GT3 infection and NASH can result in steatosis and cirrhosis, we asked whether hepatic transcriptional profiles reflective of the host response to inflammation differed based on the etiology of injury. METHODS: Hepatic gene expression was determined for 48 pre-selected genes known to be associated with hepatic interferon signaling and lipid metabolic pathways in treatment-naïve HCV GT-3 (n = 9) and NASH (n = 14) patients...
November 2016: Hepatology International
Jingshu Zhang, Daniel Man-Yuen Sze, Benjamin Yat-Ming Yung, Petrus Tang, Wei-June Chen, Kwok-Hung Chan, Polly Hang-Mei Leung
Dengue virus (DENV) infection is an emerging public health hazard threatening inhabitants of the tropics and sub-tropics. Dendritic cells (DCs) are one of the major targets of DENV and the initiators of the innate immune response against the virus. However, current in vitro research on the DENV-DC interaction is hampered by the low availability of ex vivo DCs and donor variation. In the current study, we attempted to develop a novel in vitro DC model using immature DCs derived from the myeloid leukaemia cell line MUTZ-3 (IMDCs) to investigate the DENV-DC interaction...
August 2016: Immunology
Yasuyuki Nagasawa, Daisuke Okuzaki, Eri Muso, Ryohei Yamamoto, Maki Shinzawa, Yukako Iwasaki, Hirotsugu Iwatani, Takeshi Nakanishi, Yoshitaka Isaka, Hiroshi Nojima
Diagnosis of chronic glomerulonephritis (CGN) depends primarily on renal biopsy, which is expensive and requires hospitalization, creating a demand for noninvasive diagnostic method for this disease. We used DNA microarray analysis to search for genes whose expression levels in peripheral blood mononuclear cells (PBMCs) could distinguish between patients with CGN and healthy volunteers (HVs). We selected immunoglobulin A nephropathy (IgAN) and membranous nephropathy (MN) as typical forms of CGN. The mRNA level of the gene encoding interferon (IFN)-alpha-inducible protein 27, IFI27, which is preferentially expressed in podocytes of glomeruli, was lower in PBMCs of IgAN and MN patients than in those of HVs...
2016: PloS One
Areerat Kunanopparat, Nattiya Hirankarn, Chaivat Kittigul, Pisit Tangkijvanich, Ingorn Kimkong
BACKGROUND: Autophagy-related genes ATG4B, ATG7, and ATG12 have been identified to play a critical role in viral replication. However, these genes have yet to be identified in hepatitis B virus (HBV). OBJECTIVE: To characterise the role of ATG4B, ATG7, and ATG12 genes in HBV infection. METHODS: The mRNA expression was examined by quantitative real-time RT-PCR and Western blotting. Short hairpin RNA (shRNA) of the target gene was used to examine the function of the gene in HBV replication...
March 2016: Asian Pacific Journal of Allergy and Immunology
Donghao Shang, Tiandong Han, Xiuhong Xu, Yuting Liu
OBJECTIVE: The anti-neoplastic effects of decitabine, an inhibitor of DNA promoter methylation, are beneficial for the treatment of renal cell carcinoma (RCC); however, the mechanism of action of decitabine is unclear. We analyzed gene expression profiling and identified specific pathways altered by decitabine in RCC cells. METHODS: Four human RCC cell lines (ACHN, Caki-1, Caki-1, and A498) were used in this study; growth suppression of RCC cells by decitabine was analyzed using the WST-1 assay...
2015: International Journal of Clinical and Experimental Pathology
Chike F Oguejiofor, Zhangrui Cheng, Ayimuguli Abudureyimu, Olivia L Anstaett, Joe Brownlie, Ali A Fouladi-Nashta, D Claire Wathes
Infection with noncytopathic bovine viral diarrhea virus (ncpBVDV) is associated with uterine disease and infertility. This study investigated the influence of ncpBVDV on immune functions of the bovine endometrium by testing the response to bacterial lipopolysaccharide (LPS). Primary cultures of mixed epithelial and stromal cells were divided into four treatment groups (control [CONT], BVDV, CONT+LPS, and BVDV+LPS) and infected with ncpBVDV for 4 days followed by treatment with LPS for 6 h. Whole-transcriptomic gene expression was measured followed by Ingenuity Pathway Analysis...
October 2015: Biology of Reproduction
Muhammad Atif Zahoor, Guangai Xue, Hirotaka Sato, Yoko Aida
Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that directly link the innate and adaptive immune responses. HIV-1 infection of DCs leads to a diverse array of changes in gene expression and play a major role in dissemination of the virus into T-cells. Although HIV-1 Vpr is a pleiotropic protein involved in HIV-1 replication and pathogenesis, its exact role in APCs such as DCs remains elusive. In this study, utilizing a microarray-based systemic biology approach, we found that HIV-1 Vpr differentially regulates (fold change >2...
October 2, 2015: Virus Research
Krzysztof Domagalski, Małgorzata Pawłowska, Dorota Kozielewicz, Dorota Dybowska, Andrzej Tretyn, Waldemar Halota
The strong impact of interleukin 28B (IL28B) polymorphisms on sustained virological response (SVR) after peginterferon and ribavirin treatment in patients with chronic hepatitis C (CHC) is well-known. We investigated IL28B variability and hepatic expression of IP10, IFI27, ISG15, and MX1 in CHC patients, the relation of each with their clinical characteristics, and how they associated with responses to combined therapy. Genotyping and gene expression analysis were conducted in a selected cohort of treatment-naïve patients who underwent interferon and ribavirin treatment...
2015: PloS One
Shan-Bu Xie, Xing-Xing He, Shu-Kun Yao
Matrine, one of the main extract components of Sophora flavescens, has been shown to exhibit inhibitory effects on some tumors through autophagy. However, the mechanism underlying the effect of matrine remains unclear. The cultured human hepatocellular carcinoma cell line HepG2 and SMMC‑7721 were treated with matrine. Signal transduction and gene expression profile were determined. Matrine stimulated autophagy in SMMC‑7721 cells in a mammalian target of rapamycin (mTOR)-dependent manner, but in an mTOR-independent manner in HepG2 cells...
August 2015: International Journal of Oncology
W-L Hsieh, Y-H Huang, T-M Wang, Y-C Ming, C-N Tsai, J-H S Pang
OBJECTIVES: IFI27 is highly expressed in psoriatic lesions but its function has not been known. The present study aimed to explore its role in proliferation of epidermal keratinocytes. MATERIALS AND METHODS: IFI27 knockdown and over-expression in keratinocytes were used to compare their proliferation, by MTT assay, apoptosis (by annexin V binding) and cell cycle progression by flow cytometry. Formation of cyclin A/CDK1 complex was examined by a co-immunoprecipitaion method...
April 2015: Cell Proliferation
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