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https://www.readbyqxmd.com/read/28828208/protein-microarray-analysis-identifies-key-cytokines-associated-with-malignant-middle-cerebral-artery-infarction
#1
Zhonghe Zhou, Jinghua Zhang, Xiaoqiu Li, Cheng Xia, Yaling Han, Huisheng Chen
INTRODUCTION: We aimed to explore potential cytokines involved in the malignant middle cerebral artery infarction (MMI) and elucidate their underlying regulatory mechanisms. METHODS: We first developed a cytokine profile by Quantibody(®) Human Cytokine Antibody Array7000 using serum samples from eight patients with MMI and eight patients with non-acute cerebral infarction (NACI). The differentially expressed cytokines were then identified in patients with MMI using two-tailed Student's t-test and Fisher's Exact Test compared with patients with NACI...
August 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28827704/transcriptional-dysregulation-of-interferome-in-experimental-and-human-multiple-sclerosis
#2
Sundararajan Srinivasan, Martina Severa, Fabiana Rizzo, Ramesh Menon, Elena Brini, Rosella Mechelli, Vittorio Martinelli, Paul Hertzog, Marco Salvetti, Roberto Furlan, Gianvito Martino, Giancarlo Comi, Eliana Coccia, Cinthia Farina
Recent evidence indicates that single multiple sclerosis (MS) susceptibility genes involved in interferon (IFN) signaling display altered transcript levels in peripheral blood of untreated MS subjects, suggesting that responsiveness to endogenous IFN is dysregulated during neuroinflammation. To prove this hypothesis we exploited the systematic collection of IFN regulated genes (IRG) provided by the Interferome database and mapped Interferome changes in experimental and human MS. Indeed, central nervous system tissue and encephalitogenic CD4 T cells during experimental autoimmune encephalomyelitis were characterized by massive changes in Interferome transcription...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821664/differential-desensitization-observed-at-multiple-effectors-of-somatic-mu-opioid-receptors-underlies-sustained-agonist-mediated-inhibition-of-proopiomelanocortin-neuron-activity
#3
Philip D Fox, Shane T Hentges
Activation of somatic mu opioid receptors (MORs) in hypothalamic proopiomelanocortin (POMC) neurons leads to the activation of G-protein-coupled inward rectifier potassium (GIRK) channels and hyperpolarization, but in response to continued signaling, MORs undergo acute desensitization resulting in robust reduction in the peak GIRK current after minutes of agonist exposure. We hypothesized that the attenuation of the GIRK current would lead to a recovery of neuronal excitability whereby desensitization of the receptor would lead to a new steady-state of POMC neuron activity reflecting the sustained GIRK current observed after the initial decline from peak with continued agonist exposure...
August 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28818091/non-canonical-soluble-amyloid-beta-aggregates-and-plaque-buffering-controversies-and-future-directions-for-target-discovery-in-alzheimer-s-disease
#4
REVIEW
David L Brody, Hao Jiang, Norelle Wildburger, Thomas J Esparza
The specific amyloid-beta (Aβ) species or other amyloid-precursor protein cleavage products that are most directly related to human neurodegeneration and clinical dementia of the Alzheimer's type have not yet been directly identified. Without a clear understanding of the most relevant species, it is difficult to determine whether therapeutic candidates successfully engaged the correct target(s). Here, we review some of the controversies regarding soluble Aβ aggregates (also termed oligomers, dimers, trimers, Aβ*56, amylospheroids, etc...
August 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28817646/genetic-dissection-of-endothelial-transcriptional-activity-of-zebrafish-aryl-hydrocarbon-receptors-ahrs
#5
Wade W Sugden, Roberto C Leonardo-Mendonça, Darío Acuña-Castroviejo, Arndt F Siekmann
The aryl hydrocarbon receptor (AHR) is a basic helix-loop-helix transcription factor conserved across phyla from flies to humans. Activated by a number of endogenous ligands and environmental toxins, studies on AHR function and gene regulation have largely focused on a toxicological perspective relating to aromatic hydrocarbons generated by human activities and the often-deleterious effects of exposure on vertebrates mediated by AHR activation. A growing body of work has highlighted the importance of AHR in physiologic processes, including immune cell differentiation and vascular patterning...
2017: PloS One
https://www.readbyqxmd.com/read/28815333/comparison-of-different-culture-conditions-for-smooth-muscle-cell-differentiation-of-human-umbilical-cord-vein-cd146-perivascular-cells
#6
Beyza Gökçinar-Yagci, Betül Çelebi-Saltik
Pericytes are CD146+ perivascular cells (PCs) that have multipotential differentiation capacity as mesenchymal stem cells. Beside their crucial roles in vascular development and blood flow regulation, they have ability to differentiate into vascular cell types in vivo. These properties make pericytes preferred cells in the field of vascular tissue engineering. Culture medium for in vitro differentiation of pericytes to vascular smooth muscle cells (SMCs) has not been defined yet. The aim of this study is to try different culture media for SMC differentiation of CD146+ PCs...
August 16, 2017: Cell and Tissue Banking
https://www.readbyqxmd.com/read/28814507/systematic-gene-tagging-using-crispr-cas9-in-human-stem-cells-to-illuminate-cell-organization
#7
Brock Roberts, Amanda Haupt, Andrew Tucker, Tanya Grancharova, Joy Arakaki, Margaret A Fuqua, Angelique Nelson, Caroline Hookway, Susan A Ludmann, Irina A Mueller, Ruian Yang, Alan R Horwitz, Susanne M Rafelski, Ruwanthi N Gunawardane
We present a CRISPR/Cas9 genome editing strategy to systematically tag endogenous proteins with fluorescent tags in human induced pluripotent stem cells. To date we have generated multiple human iPSC lines with monoallelic GFP tags labeling 10 proteins representing major cellular structures. The tagged proteins include alpha tubulin, beta actin, desmoplakin, fibrillarin, nuclear lamin B1, non-muscle myosin heavy chain IIB, paxillin, Sec61 beta, tight junction protein ZO1, and Tom20. Our genome editing methodology using Cas9/crRNA ribonuclear protein and donor plasmid co-electroporation, followed by fluorescence-based enrichment of edited cells, typically resulted in <0...
August 16, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28811791/differentiation-of-beta-thalassemia-trait-from-iron-deficiency-anemia-by-hematological-indices
#8
Tahir Jameel, Mukhtiar Baig, Ijaz Ahmed, Muhammad Barakat Hussain, Motlag Bin Doghaim Alkhamaly
OBJECTIVE: We aimed at finding out reliable parameter in the differentiation of iron deficiency anemia (IDA) and beta-thalassemia trait (β-TT) in the adult population subjected to Saudi Arabian Premarital Screening Program. METHODS: A total of 620 adults (age range 21-36 years) reported during February 2012 to November 2012. Tests for serum iron and ferritin were carried out in individuals showing low hemoglobin (Hb). All the selected subjects' samples were subjected to blood morphology, comparison of MCV, RBC count...
May 2017: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/28810001/deferoxamine-synergizes-with-transforming-growth-factor-%C3%AE-signaling-in-chondrogenesis
#9
Zheng Huang, Guangxu He, Yanke Huang
Osteoarthritis, also known as degenerative arthritis or degenerative joint disease, is an epidemic disease that affects millions of people worldwide. Despite extensive recent work on the cellular biology of osteoarthritis, the precise mechanisms involved are still poorly understood and there is no effective treatment for this disease. The role of transforming growth factor-beta (TGF-β) in promoting chondrogenesis and inducing the expression of cartilage-specific extracellular matrix molecules to form cartilage is well-established...
August 14, 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28807667/inhibition-of-beta-catenin-signaling-in-the-skin-rescues-cutaneous-adipogenesis-in-systemic-sclerosis-a-randomized-double-blind-placebo-controlled-trial-of-c-82
#10
Robert Lafyatis, Julio C Mantero, Jessica Gordon, Nina Kishore, Mary Carns, Howard Dittrich, Robert Spiera, Robert W Simms, John Varga
Several studies have suggested that Wnts might contribute to skin fibrosis in systemic sclerosis (SSc) by affecting the differentiation of pluripotent dermal cells. We tested C-82, a therapeutic that inhibits canonical Wnt signaling by blocking the interaction of cAMP Response Element-Binding Protein with β-Catenin and inhibiting Wnt-activated genes. We utilized previously unreported trial design, formulating C-82 for topical application and conducting a placebo controlled, double-blinded clinical trial in which patients with diffuse cutaneous SSc were treated with C-82 or placebo on opposite forearms...
August 11, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28802254/tdp1-is-critical-for-the-repair-of-dna-breaks-induced-by-sapacitabine-a-nucleoside-also-targeting-atm-and-brca-deficient-tumors
#11
Muthana Al Abo, Hiroyuki Sasanuma, Xiaojun Liu, Vinodh N Rajapakse, Shar-Yin N Huang, Evgeny Kiselev, Shunichi Takeda, William Plunkett, Yves Pommier
2'-C-cyano-2'-deoxy-1-β-D-arabino-pentofuranosylcytosine (CNDAC) is the active metabolite of the anticancer drug, sapacitabine. CNDAC is incorporated into the genome during DNA replication and subsequently undergoes beta-elimination that generates single-strand breaks with abnormal 3'-ends. Because tyrosyl-DNA phosphodiesterase 1 (TDP1) selectively hydrolyzes non-phosphorylated 3'-blocking ends, we tested its role in the repair of CNDAC-induced DNA damage. We show that cells lacking TDP1 (avian TDP1-/- DT40 cells and human TDP1 KO TSCER2 and HCT116 cells) exhibit marked hypersensitivity to CNDAC...
August 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28800317/identification-of-prostate-cancer-hub-genes-and-therapeutic-agents-using-bioinformatics-approach
#12
Enhao Fang, Xiuqing Zhang, Qi Wang, Daoming Wang
BACKGROUND: Prostate cancer (PCa) is the most common and the second leading cause of cancer-related death among men in America. As the molecular mechanism of PCa has not yet been completely discovered, identification of hub genes and potential drug of this disease is an important area of research that could provide new insights into exploring the mechanisms underlying PCa. OBJECTIVE: The aim of this study was to identify potential biomarkers and novel drug for prostate cancer treatment...
July 30, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28797129/differential-effects-of-amnion-and-chorion-membrane-extracts-on-osteoblast-like-cells-due-to-the-different-growth-factor-composition-of-the-extracts
#13
Yoon Young Go, Sung Eun Kim, Geum Joon Cho, Sung-Won Chae, Jae-Jun Song
Human amniotic membrane extracts contain numerous growth factors and bioactive substances. However, osteogenic effects of amnion and chorion membrane extracts (AME and CME, respectively) on osteoblasts are unclear. In this study, we explored the ability of AME and CME to promote the osteogenic differentiation of osteoblast-like MG-63 cells. MG-63 cells were cultured in osteogenic induction medium (OIM) with or without exogenous AME and CME. CME enhanced the osteogenic differentiation of MG-63 cells compared with AME, as indicated by increased mineralization; alkaline phosphatase activity; and mRNA expression of osteogenic marker genes encoding integrin-binding sialoprotein (IBSP), RUNX2, OSTERIX, and osteocalcin (OCN)...
2017: PloS One
https://www.readbyqxmd.com/read/28796422/insulin-producing-cells-derived-from-induced-pluripotent-stem-cells-of-patients-with-fulminant-type-1-diabetes-vulnerability-to-cytokine-insults-and-increased-expression-of-apoptosis-related-genes
#14
Yoshiya Hosokawa, Taro Toyoda, Kenji Fukui, Megu Yamaguchi Baden, Michinori Funato, Yasushi Kondo, Tomomi Sudo, Hiromi Iwahashi, Marina Kishida, Chihiro Okada, Akira Watanabe, Isao Asaka, Kenji Osafune, Akihisa Imagawa, Iichiro Shimomura
AIMS/INTRODUCTION: This study was performed to generate induced pluripotent stem cells (iPSCs) from patients with fulminant type 1 diabetes (FT1D) and evaluate the cytokine-induced apoptotic reactions of beta-like insulin-producing cells differentiated from the iPSCs. MATERIALS AND METHODS: iPSCs were generated from fibroblasts of patients with FT1D by inducing six reprogramming factors. Insulin-producing cells were differentiated from the iPSCs in vitro. The proportion of cleaved caspase-3-positive or TUNEL-positive cells among INSULIN (INS)-positive cells derived from FT1D-iPSC and control human-iPSC lines was evaluated under treatment with tumor necrosis factor-alpha, interleuin-1-beta, and interferon-gamma...
August 10, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28796338/benign-and-malignant-hybrid-adnexal-tumors-in-a-patient-with-epidermodysplasia-verruciformis
#15
Jonathan Ho, Sarah A Kam, Ali Al-Haseni, Alina Markova, Debjani Sahni, Christina Lam, Lynne J Goldberg, Jag Bhawan
Epidermodysplasia verruciformis (EV) is a genodermatosis characterized by overgrowth of flat warts, pityriasis versicolor-like lesions and an increased propensity for developing cutaneous squamous cell carcinomas due to abnormal susceptibility to infection with beta-human papilloma viruses. Adnexal tumors are not typically associated with EV. Here we report a spectrum of hybrid adnexal tumors with divergent eccrine and folliculosebaceous differentiation, and cytologic features ranging from benign to frankly atypical, in a patient with inherited EV...
August 10, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28796060/candidate-genes-investigation-for-severe-nonalcoholic-fatty-liver-disease-based-on-bioinformatics-analysis
#16
Shan Qi, Changhong Wang, Chunfu Li, Pu Wang, Minghui Liu
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver condition worldwide. However, its etiology and fundamental pathophysiology for the disease process are poorly understood. In this study, we thus used bioinformatics to identify candidate genes potentially causative of severe NAFLD. METHODS: Gene expression profile data GSE49541 were downloaded from the Gene Expression Omnibus database. Tissues samples from 32 severe and 40 mild NAFLD patients were evaluated to identify differentially expressed genes (DEGs) between the 2 groups, followed by analyses of Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes pathways...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28794034/an-epstein-barr-virus-microrna-blocks-il-1-signaling-by-targeting-the-interleukin-1-receptor-1
#17
Camille M Skinner, Nikita S Ivanov, Sarah A Barr, Yan Chen, Rebecca L Skalsky
Epstein-Barr virus (EBV) encodes >44 viral microRNAs (miRNAs) that are differentially expressed throughout infection, can be detected in EBV-positive tumors, and manipulate several biological processes including cell proliferation, apoptosis, and immune responses. Here, we show that EBV BHRF1-2 miRNAs block NF-kB activation following treatment with pro-inflammatory cytokines, specifically interleukin-1 beta. Analysis of EBV PAR-CLIP miRNA targetome datasets combined with pathway analysis revealed multiple BHRF1-2 miRNA targets involved in interleukin signaling pathways...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28792951/how-stable-is-repression-of-disallowed-genes-in-pancreatic-islets-in-response-to-metabolic-stress
#18
Katleen Lemaire, Mikaela Granvik, Anica Schraenen, Lotte Goyvaerts, Leentje Van Lommel, Ana Gómez-Ruiz, Peter In 't Veld, Patrick Gilon, Frans Schuit
The specific phenotype of mature differentiated beta cells not only depends on the specific presence of genes that allow beta cell function but also on the selective absence of housekeeping genes ("disallowed genes") that would interfere with this function. Recent studies have shown that both histone modifications and DNA methylation via the de novo methyltransferase DNMT3A are involved in repression of disallowed genes in neonatal beta cells when these cells acquire their mature phenotype. It is unknown, however, if the environmental influence of advanced age, pregnancy and the metabolic stress of high fat diet or diabetes could alter the repression of disallowed genes in beta cells...
2017: PloS One
https://www.readbyqxmd.com/read/28791439/metabolic-crosstalk-between-fatty-pancreas-and-fatty-liver-effects-on-local-inflammation-and-insulin-secretion
#19
Felicia Gerst, Robert Wagner, Gabriele Kaiser, Madhura Panse, Martin Heni, Jürgen Machann, Malte N Bongers, Tina Sartorius, Bence Sipos, Falko Fend, Christian Thiel, Silvio Nadalin, Alfred Königsrainer, Norbert Stefan, Andreas Fritsche, Hans-Ulrich Häring, Susanne Ullrich, Dorothea Siegel-Axel
AIMS/HYPOTHESIS: Obesity-linked ectopic fat accumulation is associated with the development of type 2 diabetes. Whether pancreatic and liver steatosis impairs insulin secretion is controversial. We examined the crosstalk of human pancreatic fat cells with islets and the role of diabetogenic factors, i.e. palmitate and fetuin-A, a hepatokine released from fatty liver. METHODS: Human pancreatic resections were immunohistochemically stained for insulin, glucagon, somatostatin and the macrophage/monocyte marker CD68...
August 8, 2017: Diabetologia
https://www.readbyqxmd.com/read/28780694/dose-rate-effects-of-low-let-ionizing-radiation-on-fish-cells
#20
Nguyen T K Vo, Colin B Seymour, Carmel E Mothersill
Radiobiological responses of a highly clonogenic fish cell line, eelB, to low-LET ionizing radiation and effects of dose rates were studied. In acute exposure to 0.1-12 Gy of gamma rays, eelB's cell survival curve displayed a linear-quadratic (LQ) relationship. In the LQ model, α, β, and α/β ratio were 0.0024, 0.037, and 0.065, respectively; for the first time that these values were reported for fish cells. In the multi-target model, n, D o, and D q values were determined to be 4.42, 2.16, and 3.21 Gy, respectively, and were the smallest among fish cell lines being examined to date...
August 5, 2017: Radiation and Environmental Biophysics
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