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Melinda J Murphy, Nathan G Halow, Pamela A Royer, Jon D Hennebold
Although the requirement of pituitary-derived luteinizing hormone (LH) for ovulation is well documented, the intrafollicular paracrine and autocrine processes elicited by LH necessary for follicle rupture are not fully understood. Evaluating a published rhesus macaque periovulatory transcriptome database revealed that mRNA encoding leukemia inhibitory factor (LIF) and its downstream signaling effectors are upregulated in the follicle after animals receive an ovulatory stimulus (human chorionic gonadotropin; hCG)...
August 29, 2016: Endocrinology
Sabine Ringkowski, Joshua Loke, Shuying Huang, Hasib Ahmadzai, Felix J F Herth, Paul S Thomas, Cristan Herbert
RATIONALE: Granulomas in sarcoidosis have recently been described as containing Interleukin (IL)-27, one of the members of the IL-12 family of cytokines, which also includes IL-35. Levels of these cytokines and the IL-27 receptor subunits were hypothesised to differ between patients with sarcoidosis compared to healthy controls in peripheral blood. METHODS: Using a cross-sectional study design, plasma and peripheral blood mononuclear cells (PBMC) were collected from patients and control subjects...
August 2016: Respiratory Medicine
Thomas Harwardt, Simone Lukas, Marion Zenger, Tobias Reitberger, Daniela Danzer, Theresa Übner, Diane C Munday, Michael Nevels, Christina Paulus
The human cytomegalovirus (hCMV) major immediate-early 1 protein (IE1) is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNγ...
July 2016: PLoS Pathogens
Su-Jeong Kim, Noel Guerrero, Gabriella Wassef, Jialin Xiao, Hemal H Mehta, Pinchas Cohen, Kelvin Yen
Humanin is a small secreted peptide that is encoded in the mitochondrial genome. Humanin and its analogues have a protective role in multiple age-related diseases including type 2 diabetes and Alzheimer's disease, through cytoprotective and neuroprotective effects both in vitro and in vivo. However, the humanin-mediated signaling pathways are not well understood. In this paper, we demonstrate that humanin acts through the GP130/IL6ST receptor complex to activate AKT, ERK1/2, and STAT3 signaling pathways. Humanin treatment increases phosphorylation in AKT, ERK 1/2, and STAT3 where PI3K, MEK, and JAK are involved in the activation of those three signaling pathways, respectively...
July 1, 2016: Oncotarget
Reiko Kawase, Yuhei Nishimura, Yoshifumi Ashikawa, Shota Sasagawa, Soichiro Murakami, Mizuki Yuge, Shiko Okabe, Koki Kawaguchi, Hiroshi Yamamoto, Kazumi Moriyuki, Shinsaku Yamane, Kazuhiro Tsuruma, Masamitsu Shimazawa, Hideaki Hara, Toshio Tanaka
Exposure of rhodopsin to bright white light can induce photoreceptor cell damage and degeneration. However, a comprehensive understanding of the mechanisms underlying light-induced retinopathy remains elusive. In this study, we performed comparative transcriptome analysis of three rodent models of light-induced retinopathy, and we identified 37 genes that are dysregulated in all three models. Gene ontology analysis revealed that this gene set is significantly associated with a cytokine signaling axis composed of signal transducer and activator of transcription 1 and 3 (STAT1/3), interleukin 6 signal transducer (IL6ST), and oncostatin M receptor (OSMR)...
2016: Frontiers in Pharmacology
Florian Handle, Holger H H Erb, Birgit Luef, Julia Hoefer, Dimo Dietrich, Walther Parson, Glen Kristiansen, Frédéric R Santer, Zoran Culig
UNLABELLED: The proinflammatory cytokine IL6 is associated with bad prognosis in prostate cancer and implicated in progression to castration resistance. Suppressor of cytokine signaling 3 (SOCS3) is an IL6-induced negative feedback regulator of the IL6/Janus kinase (JAK)/STAT3 pathway. This study reveals that the SOCS3 promoter is hypermethylated in cancerous regions compared with adjacent benign tissue in prostate cancer using methylation-specific qPCR. A series of in vitro experiments was performed to assess the functional impact of low SOCS3 expression during anti-androgen treatment...
June 2016: Molecular Cancer Research: MCR
Sonja M Wörmann, Liang Song, Jiaoyu Ai, Kalliope N Diakopoulos, Magdalena U Kurkowski, Kivanc Görgülü, Dietrich Ruess, Andrew Campbell, Claudio Doglioni, Duncan Jodrell, Albrecht Neesse, Ihsan E Demir, Angelica-Phaedra Karpathaki, Maxim Barenboim, Thorsten Hagemann, Stefan Rose-John, Owen Sansom, Roland M Schmid, Maria P Protti, Marina Lesina, Hana Algül
BACKGROUND & AIMS: One treatment strategy for pancreatic ductal adenocarcinoma is to modify, rather than deplete, the tumor stroma. Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) is associated with progression of pancreatic and other solid tumors. We investigated whether loss of P53 function contributes to persistent activation of STAT3 and modification of the pancreatic tumor stroma in patients and mice. METHODS: Stat3, Il6st (encodes gp130), or Trp53 were disrupted, or a mutant form of P53 (P53R172H) or transgenic sgp130 were expressed, in mice that developed pancreatic tumors resulting from expression of activated KRAS (KrasG12D, KC mice)...
July 2016: Gastroenterology
Xiang Li, Shiwei Li, Mize Lu, Guohua Yang, Yunfeng Shen, Xin Zhou
BACKGROUND: Hepatic iron overload is common in patients who have undergone hematopoietic cell transplantation (HCT) and may predispose to peri- and post-HCT toxicity. To better reveal more molecules that might be involved in iron overload-induced liver injury, we utilized proteomics to investigate differentially expressed proteins in iron overload-induced hepatocytes vs. untreated hepatocytes. METHODS AND RESULTS: HH4 hepatocytes were exposed to ferric ammonium citrate (FAC) to establish an in vitro iron overload model...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Aleksandar Vojta, Paula Dobrinić, Vanja Tadić, Luka Bočkor, Petra Korać, Boris Julg, Marija Klasić, Vlatka Zoldoš
Epigenetic studies relied so far on correlations between epigenetic marks and gene expression pattern. Technologies developed for epigenome editing now enable direct study of functional relevance of precise epigenetic modifications and gene regulation. The reversible nature of epigenetic modifications, including DNA methylation, has been already exploited in cancer therapy for remodeling the aberrant epigenetic landscape. However, this was achieved non-selectively using epigenetic inhibitors. Epigenetic editing at specific loci represents a novel approach that might selectively and heritably alter gene expression...
July 8, 2016: Nucleic Acids Research
Taro Koyama, Kazuhiro Kobayashi, Takanori Hama, Kasumi Murakami, Rei Ogawa
OBJECTIVE: In this study, we evaluated the effect of scalp massage on hair in Japanese males and the effect of stretching forces on human dermal papilla cells in vitro. METHODS: Nine healthy men received 4 minutes of standardized scalp massage per day for 24 weeks using a scalp massage device. Total hair number, hair thickness, and hair growth rate were evaluated. The mechanical effect of scalp massage on subcutaneous tissue was analyzed using a finite element method...
2016: Eplasty
Stefan Thiem, Moritz F Eissmann, Joachim Elzer, Anna Jonas, Tracy L Putoczki, Ashleigh Poh, Paul Nguyen, Adele Preaudet, Dustin Flanagan, Elizabeth Vincan, Paul Waring, Michael Buchert, Andrew Jarnicki, Matthias Ernst
About 5% to 10% of human gastric tumors harbor oncogenic mutations in the KRAS pathway, but their presence alone is often insufficient for inducing gastric tumorigenesis, suggesting a requirement for additional mutagenic events or microenvironmental stimuli, including inflammation. Assessing the contribution of such events in preclinical mouse models requires Cre recombinase-mediated conditional gene expression in stem or progenitor cells of normal and transformed gastric epithelium. We therefore constructed a bacterial artificial chromosome containing transgene (Tg), comprising the regulatory elements of the trefoil factor 1 (Tff1) gene and the tamoxifen-inducible Cre recombinase (CreERT2)-coding sequence...
April 15, 2016: Cancer Research
Justin J-L Wong, Amy Y M Au, Dadi Gao, Natalia Pinello, Chau-To Kwok, Annora Thoeng, Katherine A Lau, Jane E A Gordon, Ulf Schmitz, Yue Feng, Trung V Nguyen, Robert Middleton, Charles G Bailey, Jeff Holst, John E J Rasko, William Ritchie
Fever is commonly used to diagnose disease and is consistently associated with increased mortality in critically ill patients. However, the molecular controls of elevated body temperature are poorly understood. We discovered that the expression of RNA-binding motif protein 3 (RBM3), known to respond to cold stress and to modulate microRNA (miRNA) expression, was reduced in 30 patients with fever, and in THP-1-derived macrophages maintained at a fever-like temperature (40 °C). Notably, RBM3 expression is reduced during fever whether or not infection is demonstrable...
April 7, 2016: Nucleic Acids Research
Gavin D Brooks, Louise McLeod, Sultan Alhayyani, Alistair Miller, Prudence A Russell, Walter Ferlin, Stefan Rose-John, Saleela Ruwanpura, Brendan J Jenkins
Oncogenic KRAS mutations occur frequently in lung adenocarcinoma. The signaling pathways activated by IL6 promote Kras-driven lung tumorigenesis, but the basis for this cooperation is uncertain. In this study, we used the gp130(F/F) (Il6st) knock-in mouse model to examine the pathogenic contribution of hyperactivation of the STAT3 arm of IL6 signaling on KRAS-driven lung tumorigenesis. Malignant growths in the gp130(F/F):Kras(G12D) model displayed features of atypical adenomatous hyperplasia, adenocarcinoma in situ, and invasive adenocarcinoma throughout the lung, as compared with parental Kras(G12D) mice, where STAT3 was not hyperactivated...
February 15, 2016: Cancer Research
Joseph Ignatius Irudayam, Deisy Contreras, Lindsay Spurka, Songyang Ren, Vidhya Kanagavel, Arunachalam Ramaiah, Alagappan Annamalai, Samuel W French, Andrew S Klein, Vincent Funari, Vaithilingaraja Arumugaswami
Expression of genes associated with inflammation was analyzed during differentiation of human pluripotent stem cells (PSCs) to hepatic cells. Messenger RNA transcript profiles of differentiated endoderm (day 5), hepatoblast (day 15) and hepatocyte-like cells (day 21) were obtained by RNA sequencing analysis. When compared to endoderm cells an immature cell type, the hepatic cells (days 15 and 21) had significantly higher expression of acute phase protein genes including complement factors, coagulation factors, serum amyloid A and serpins...
December 2015: Data in Brief
Alexander Schwickert, Esther Weghake, Kathrin Brüggemann, Annika Engbers, Benjamin F Brinkmann, Björn Kemper, Jochen Seggewiß, Christian Stock, Klaus Ebnet, Ludwig Kiesel, Christoph Riethmüller, Martin Götte
MicroRNAs (miRNAs, micro ribonucleic acids) are pivotal post-transcriptional regulators of gene expression. These endogenous small non-coding RNAs play significant roles in tumorigenesis and tumor progression. miR-142-3p expression is dysregulated in several breast cancer subtypes. We aimed at investigating the role of miR-142-3p in breast cancer cell invasiveness. Supported by transcriptomic Affymetrix array analysis and confirmatory investigations at the mRNA and protein level, we demonstrate that overexpression of miR-142-3p in MDA-MB-231, MDA-MB-468 and MCF-7 breast cancer cells leads to downregulation of WASL (Wiskott-Aldrich syndrome-like, protein: N-WASP), Integrin-αV, RAC1, and CFL2, molecules implicated in cytoskeletal regulation and cell motility...
2015: PloS One
N Senhaji, A Serrano, W Badre, N Serbati, M Karkouri, Y Zaid, S Nadifi, J Martin
The purpose of this study was to investigate whether common variants in inflammatory and immune response genes influence inflammatory bowel disease (IBD) risk among Moroccan patients. Using a candidate gene approach, 10 single-nucleotide polymorphisms mapping on six genes (MIF_rs755622, TNFA_rs1800629, IL6_rs2069840, IL6R_rs2228145, IL6ST_rs2228044, IL17A (rs2275913, rs4711998, rs7747909, rs8193036, rs3819024)) were assessed in 510 subjects grouped in 199 IBD and 311 healthy controls. Genotyping was performed with the TaqMan allelic discrimination technology...
January 2016: Genes and Immunity
Julien Calderaro, Jean C Nault, Charles Balabaud, Gabrielle Couchy, Marie-Christine Saint-Paul, Daniel Azoulay, Dalila Mehdaoui, Alain Luciani, Elie S Zafrani, Paulette Bioulac-Sage, Jessica Zucman-Rossi
Hepatocellular adenoma is considered to occur exclusively in non-fibrotic livers. It is a heterogeneous entity and a molecular classification is now widely accepted. The most frequent hepatocellular adenoma subtype, namely inflammatory adenoma, harbor somatic activating mutations of genes involved in the interleukin-6 pathway that lead to high C-reactive protein and serum amyloid A expression. The aim of our study was to investigate a series of benign hepatocellular neoplasms developed on cirrhotic livers and characterized by an unequivocal histological diagnosis...
January 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Vladan P Čokić, Olivera Mitrović-Ajtić, Bojana B Beleslin-Čokić, Dragana Marković, Marijana Buač, Miloš Diklić, Nada Kraguljac-Kurtović, Svetozar Damjanović, Pavle Milenković, Mirjana Gotić, Puri K Raj
The recent JAK1/2 inhibitor trial in myeloproliferative neoplasms (MPNs) showed that reducing inflammation can be more beneficial than targeting gene mutants. We evaluated the proinflammatory IL-6 cytokine and JAK-STAT signaling pathway related genes in circulating CD34(+) cells of MPNs. Regarding laboratory data, leukocytosis has been observed in polycythemia vera (PV) and JAK2V617F mutation positive versus negative primary myelofibrosis (PMF) patients. Moreover, thrombocytosis was reduced by JAK2V617F allele burden in essential thrombocythemia (ET) and PMF...
2015: Mediators of Inflammation
Susanne Schulz, Uta Dorothee Immel, Louise Just, Hans-Günter Schaller, Christiane Gläser, Stefan Reichert
BACKGROUND: Periodontitis is a chronic inflammatory disease triggered by the host immune response. Epigenetic modifications also affect the immune response. We assessed CpG methylation in 22 inflammatory candidate genes (ATF2, CCL25, CXCL14, CXCL3, CXCL5, CXCL6, FADD, GATA3, IL10RA, IL12A, IL12B, IL13, IL13RA1, IL15, IL17C, IL17RA, IL4R, IL6R, IL6ST, IL7, INHA, and TYK2) with respect to the occurrence of aggressive periodontitis (AgP). PATIENTS AND METHODS: In this study 15 AgP patients (53...
January 2016: Human Immunology
Gustavo Freitas Ilha, Monique T Rovani, Bernardo G Gasperin, Alfredo Quites Antoniazzi, Paulo Bayard Dias Gonçalves, Vilceu Bordignon, Raj Duggavathi
Subordinate follicles (SFs) of bovine follicular waves undergo atresia due to declining FSH concentrations; however, the signalling mechanisms have not been fully deciphered. We used an FSH-induced co-dominance model to determine the effect of FSH on signalling pathways in granulosa cells of the second-largest follicles (SF in control cows and co-dominant follicle (co-DF2) in FSH-treated cows). The SF was smaller than DF in control cows while diameters of co-DF1 and co-DF2 in FSH-treated cows were similar. The presence of cleaved CASP3 protein confirmed that granulosa cells of SFs, but not of DFs and co-DFs, were apoptotic...
October 2015: Reproduction: the Official Journal of the Society for the Study of Fertility
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