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José Carlos Ribeiro DE Araujo, Jorge José DE Carvalho, Humberto Oliveira Serra
OBJECTIVE: to evaluate the influence of Duodenal reflux in histological changes of the gastric mucosa of rats infected with Helicobacter pylori submitted to pyloroplasty. METHODS: after two weeks of acclimation, we infected 30 male Wistar rats with Helicobacter pylori. We randomly divided them into three groups: one submitted to pyloroplasty, another to partial gastrectomy and the third, only infected, was not operated. After six months of surgery, euthanasia was carried out...
July 2016: Revista do Colégio Brasileiro de Cirurgiões
Luke B Hesson, Benedict Ng, Peter Zarzour, Sameer Srivastava, Chau-To Kwok, Deborah Packham, Andrea C Nunez, Dominik Beck, Regina Ryan, Ashraf Dower, Caroline E Ford, John Pimanda, Mathew A Sloane, Nicholas J Hawkins, Michael J Bourke, Jason W H Wong, Robyn L Ward
: Laterally spreading tumors (LSTs) are colorectal adenomas that develop into extremely large lesions with predominantly slow progression to cancer depending on lesion subtype. Comparing and contrasting the molecular profiles of LSTs and colorectal cancer (CRCs) offers an opportunity to delineate key molecular alterations that drive malignant transformation in the colorectum. In a discovery cohort of 11 LSTs and paired normal mucosa, we performed a comprehensive and unbiased screen of the genome, epigenome and transcriptome followed by bioinformatics integration of these data and validation in an additional 84 large benign colorectal lesions...
September 26, 2016: Molecular Cancer Research: MCR
Ekaterina Balaian, Claudia Schuster, Claudia Schönefeldt, Ulrich Germing, Detlef Haase, Sebastian Tuve, Rainer Ordemann, Gerhard Ehninger, Martin Bornhäuser, Uta Oelschlaegel, Brigitte Mohr, Malte von Bonin, Uwe Platzbecker, Martin Wermke
Lenalidomide (LEN) leads to erythroid improvement in the majority of patients with myelodysplastic syndrome and isolated deletion of the long arm of chromosome 5 (MDS-del(5q)). This effect is believed to be exerted via its immunomodulatory properties, although the precise nature is still incompletely understood. We prospectively performed immune profiling in the bone marrow and blood of MDS-del(5q) patients undergoing LEN therapy for a median of 6 cycles. Therapy with LEN led to a significant increase in the median absolute lymphocyte count (1...
October 2016: Annals of Hematology
Yves-Marie Pers, Pierre Le Blay, Catherine Ludwig, Cécile Rittore, Gautier Tejedor, Randy Foliwe, Michel Rodiere, Christian Jorgensen, Isabelle Touitou
OBJECTIVES: Numerous single nucleotide polymorphisms (SNPs) have been associated with JIA, but few of these studies were replicated. We conducted a candidate-gene approach study to assess if some SNPs could be related to clinical subtypes or other clinical features of the juvenile idiopathic arthritis (JIA) such as the risk of uveitis, ANA positivity and the age at onset. METHODS: SNPs in six genes were analysed: PTPN22, STAT4, TRAF1-C5, TGFbeta, TNFAIP3, and C12orf30...
June 28, 2016: Joint, Bone, Spine: Revue du Rhumatisme
Amanda Rodriguez, Swamy K Tripurani, Jason C Burton, Caterina Clementi, Irina Larina, Stephanie A Pangas
Pregnancy is a complex physiological process tightly controlled by the interplay among hormones, morphogens, transcription factors, and signaling pathways. Although recent studies using genetically engineered mouse models have revealed that ligands and receptors of transforming growth factor beta (TGFbeta) and bone morphogenetic protein (BMP) signaling pathways are essential for multiple reproductive events during pregnancy, the functional role of SMAD transcription factors, which serve as the canonical signaling platform for the TGFbeta/BMP pathways, in the oviduct and uterus is undefined...
August 2016: Biology of Reproduction
Elisabeth M Meier, Lisa Rein-Fischboeck, Rebekka Pohl, Josef Wanninger, Andrew J Hoy, Thomas Grewal, Kristina Eisinger, Sabrina Krautbauer, Gerhard Liebisch, Thomas S Weiss, Christa Buechler
Annexin A6 (AnxA6) is a lipid-binding protein highly expressed in the liver, regulating cholesterol homeostasis and signaling pathways with a role in liver physiology. Here, we analyzed whether hepatic AnxA6 levels are affected by pathological conditions that are associated with liver dysfunction and liver injury. AnxA6 levels in the fatty liver of mice fed a high-fat diet, in ob/ob and db/db animals and in human fatty liver are comparable to controls. Similarly, AnxA6 levels appear unaffected in murine nonalcoholic steatohepatitis and human liver fibrosis...
July 2016: Molecular and Cellular Biochemistry
Damir Jacob Illich, Miao Zhang, Andrei Ursu, Rodrigo Osorno, Kee-Pyo Kim, Juyong Yoon, Marcos J Araúzo-Bravo, Guangming Wu, Daniel Esch, Davood Sabour, Douglas Colby, Kathrin S Grassme, Jiayu Chen, Boris Greber, Susanne Höing, Wiebke Herzog, Slava Ziegler, Ian Chambers, Shaorong Gao, Herbert Waldmann, Hans R Schöler
It has previously been reported that mouse epiblast stem cell (EpiSC) lines comprise heterogeneous cell populations that are functionally equivalent to cells of either early- or late-stage postimplantation development. So far, the establishment of the embryonic stem cell (ESC) pluripotency gene regulatory network through the widely known chemical inhibition of MEK and GSK3beta has been impractical in late-stage EpiSCs. Here, we show that chemical inhibition of casein kinase 1alpha (CK1alpha) induces the conversion of recalcitrant late-stage EpiSCs into ESC pluripotency...
April 14, 2016: Cell Reports
Maïté Noizet, Emilie Lagoutte, Marlène Gratigny, Marielle Bouschbacher, Isabelle Lazareth, Hugues Roest Crollius, Xavier Darzacq, Claire Dugast-Darzacq
Fibroblasts are important players in regulating tissue homeostasis. In the dermis, they are involved in wound healing where they differentiate into contractile myofibroblasts leading to wound closure. In nonhealing chronic wounds, fibroblasts fail to undertake differentiation. We established and used a human ex vivo model of chronic wounds where fibroblasts can undergo normal myofibroblast differentiation, or take on a nondifferentiable pathological state. At the whole genome scale, we identified the genes that are differentially regulated in these two cell fates...
March 2016: Wound Repair and Regeneration
Antonis Vlismas, Ritsa Bletsa, Despina Mavrogianni, Georgina Mamali, Maria Pergamali, Vasiliki Dinopoulou, George Partsinevelos, Peter Drakakis, Dimitris Loutradis, Ann A Kiessling
Previous microarray analyses of RNAs from 8-cell (8C) human embryos revealed a lack of cell cycle checkpoints and overexpression of core circadian oscillators and cell cycle drivers relative to pluripotent human stem cells [human embryonic stem cells/induced pluripotent stem (hES/iPS)] and fibroblasts, suggesting growth factor independence during early cleavage stages. To explore this possibility, we queried our combined microarray database for expression of 487 growth factors and receptors. Fifty-one gene elements were overdetected on the 8C arrays relative to hES/iPS cells, including 14 detected at least 80-fold higher, which annotated to multiple pathways: six cytokine family (CSF1R, IL2RG, IL3RA, IL4, IL17B, IL23R), four transforming growth factor beta (TGFB) family (BMP6, BMP15, GDF9, ENG), one fibroblast growth factor (FGF) family [FGF14(FH4)], one epidermal growth factor member (GAB1), plus CD36, and CLEC10A...
January 15, 2016: Stem Cells and Development
Helle Sadam, Urmas Liivas, Anna Kazantseva, Priit Pruunsild, Jekaterina Kazantseva, Tõnis Timmusk, Toomas Neuman, Kaia Palm
High activity of GLI family zinc finger protein 2 (GLI2) promotes tumor progression. Removal of the repressor domain at the N terminus (GLI2∆N) by recombinant methods converts GLI2 into a powerful transcriptional activator. However, molecular mechanisms leading to the formation of GLI2∆N activator proteins have not been established. Herein we report for the first time that the functional activities of GLI2 are parted into different protein isoforms by alternative promoter usage, selection of alternative splicing, transcription initiation and termination sites...
January 2016: Biochimica et Biophysica Acta
Christopher P Denton
Systemic sclerosis (scleroderma) leads to morbidity and mortality through a combination of inflammation, fibrosis and vascular damage leading to internal organ complications affecting the heart, lung, kidneys and bowel. More than half of those diagnosed ultimately die from the disease. Current treatments focus on broad spectrum immunosuppression or organ-based therapy for complication such as lung fibrosis, pulmonary or systemic hypertension. Targeting peptide mediators such as endothelin-1 have already led to licensed effective therapies for SSc vasculopathy...
July 2015: Clinical and Experimental Rheumatology
Yulei Zhao, Xiaolong Yang
WWTR1 (also called TAZ in publications. Therefore, TAZ is used in the following description) is a WW domaing-containing transcriptional coactivator, which was first identified as a 14-3-3 binding protein. TAZ is the downstream component in the Hippo pathway, and also has been found to interact with different pathways, such as Wnt, TGFbeta, etc. TAZ is involved in mesenchymal stem cell differentiation as well as tumorigenesis. High level of TAZ has been found in different cancers, such as breast cancer, colon cancer, lung cancer, etc...
November 1, 2014: Atlas of Genetics and Cytogenetics in Oncology and Haematology
Sebastian Fischer, Tobias Hirsch, Yannick Diehm, Jurij Kiefer, Ericka M Bueno, Maximilian Kueckelhaus, Thomas Kremer, Christoph Hirche, Ulrich Kneser, Bohdan Pomahac
BACKGROUND: The main part of the fibrotic capsule in capsular contracture is collagen. The collagenase of the bacterium Clostridium histolyticum is U.S. Food and Drug Administration approved for the treatment of Dupuytren contracture and might be capable of dissolving the fibrotic capsule surrounding silicone implants. METHODS: One hundred twenty days after insertion of miniature silicone implants the authors performed in vitro studies (n = 14) for optimum dosage-finding and subsequent in vivo studies (n = 36) to evaluate application method and efficiency...
November 2015: Plastic and Reconstructive Surgery
Rie Fujita, Nobuo Koizumi, Hiromu Sugiyama, Rina Tomizawa, Ryoichi Sato, Makoto Ohnishi
Leptospirosis, a zoonotic infection with worldwide prevalence, is caused by pathogenic spirochaetes of Leptospira spp., and exhibits an extremely broad clinical spectrum in human patients. Although previous studies indicated that specific serovars or genotypes of Leptospira spp. were associated with severe leptospirosis or its outbreak, the mechanism underlying the difference in virulence of the various Leptospira serotypes or genotypes remains unclear. The present study addresses this question by measuring and comparing bacterial burden and cytokine gene expression in hamsters infected with strains of two L...
2015: PloS One
A Grilli, M Sciandra, M Terracciano, P Picci, K Scotlandi
BACKGROUND: microRNAs (miRs) are small non-coding RNAs involved in the fine regulation of several cellular processes by inhibiting their target genes at post-transcriptional level. Osteosarcoma (OS) is a tumor thought to be related to a molecular blockade of the normal process of osteoblast differentiation. The current paper explores temporal transcriptional modifications comparing an osteosarcoma cell line, Saos-2, and clones stably transfected with CD99, a molecule which was found to drive OS cells to terminally differentiate...
2015: BMC Medical Genomics
Abdulrzag F Ahmed, Charles E de Bock, Lisa F Lincz, Jay Pundavela, Ihssane Zouikr, Estelle Sontag, Hubert Hondermarck, Rick F Thorne
The Hippo pathway is emerging as a critical nexus that balances self-renewal of progenitors against differentiation; however, upstream elements in vertebrate Hippo signalling are poorly understood. High expression of Fat1 cadherin within the developing neuroepithelium and the manifestation of severe neurological phenotypes in Fat1-knockout mice suggest roles in neurogenesis. Using the SH-SY5Y model of neuronal differentiation and employing gene silencing techniques, we show that FAT1 acts to control neurite outgrowth, also driving cells towards terminal differentiation via inhibitory effects on proliferation...
December 2015: Cellular and Molecular Life Sciences: CMLS
Rosalinda Madonna, Christian Cadeddu, Martino Deidda, Zoltán Giricz, Clelia Madeddu, Donato Mele, Ines Monte, Giuseppina Novo, Pasquale Pagliaro, Alessia Pepe, Paolo Spallarossa, Carlo Gabriele Tocchetti, Zoltán V Varga, Concetta Zito, Yong-Jian Geng, Giuseppe Mercuro, Peter Ferdinandy
Ischemic heart disease remains the leading cause of death worldwide. Ischemic pre-, post-, and remote conditionings trigger endogenous cardioprotection that renders the heart resistant to ischemic-reperfusion injury (IRI). Mimicking endogenous cardioprotection by modulating genes involved in cardioprotective signal transduction provides an opportunity to reproduce endogenous cardioprotection with better possibilities of translation into the clinical setting. Genes and signaling pathways by which conditioning maneuvers exert their effects on the heart are partially understood...
July 15, 2015: International Journal of Cardiology
Camilla Evangelisti, Pia Bernasconi, Paola Cavalcante, Cristina Cappelletti, Maria Rosaria D'Apice, Paolo Sbraccia, Giuseppe Novelli, Sabino Prencipe, Silvia Lemma, Nicola Baldini, Sofia Avnet, Stefano Squarzoni, Alberto M Martelli, Giovanna Lattanzi
Transforming growth factor beta (TGFbeta) plays an essential role in bone homeostasis and deregulation of TGFbeta occurs in bone pathologies. Patients affected by Mandibuloacral Dysplasia (MADA), a progeroid disease linked to LMNA mutations, suffer from an osteolytic process. Our previous work showed that MADA osteoblasts secrete excess amount of TGFbeta 2, which in turn elicits differentiation of human blood precursors into osteoclasts. Here, we sought to determine how altered lamin A affects TGFbeta signaling...
April 10, 2015: Oncotarget
Adam C Midgley, Lucy Duggal, Robert Jenkins, Vincent Hascall, Robert Steadman, Aled O Phillips, Soma Meran
Hyaluronan (HA) promotes transforming growth factor (TGF)-β1-driven myofibroblast phenotype. However, HA can also have disease-limiting activity. Bone morphogenetic protein-7 (BMP7) is an antifibrotic cytokine that antagonizes TGF-β1, and isolated studies have demonstrated that HA can both mediate and modulate BMP7 responses. In this study, we investigated whether BMP7 can modulate HA in a manner that leads to prevention/reversal of TGF-β1-driven myofibroblast differentiation in human lung fibroblasts. Results demonstrated that BMP7 prevented and reversed TGF-β1-driven myofibroblast differentiation through a novel mechanism...
May 1, 2015: Journal of Biological Chemistry
Amanda L Balboni, Pratima Cherukuri, Matthew Ung, Andrew J DeCastro, Chao Cheng, James DiRenzo
UNLABELLED: The TGFβ superfamily regulates a broad range of cellular processes, including proliferation, cell-fate specification, differentiation, and migration. Molecular mechanisms underlying this high degree of pleiotropy and cell-type specificity are not well understood. The TGFβ family is composed of two branches: (i) TGFβs, activins, and nodals, which signal through SMAD2/3, and (ii) bone morphogenetic proteins (BMP), which signal through SMAD1/5/8. SMADs have weak DNA-binding affinity and rely on coactivators and corepressors to specify their transcriptional outputs...
April 2015: Molecular Cancer Research: MCR
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