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Ping Tsui, Daniel R Higazi, Yanli Wu, Rebecca Dunmore, Emilie Solier, Toyin Kasali, Nicholas J Bond, Catherine Huntington, Alan Carruthers, John Hood, M Jack Borrok, Arnita Barnes, Keith Rickert, Sandrina Phipps, Lena Shirinian, Jie Zhu, Michael A Bowen, William Dall'Acqua, Lynne A Murray
Excessive transforming growth factor (TGF)-β is associated with pro-fibrotic responses in lung disease, yet it also plays essential roles in tissue homeostasis and autoimmunity. Therefore, selective inhibition of excessive and aberrant integrin-mediated TGF-β activation via targeting the alpha-v family of integrins is being pursued as a therapeutic strategy for chronic lung diseases, to mitigate any potential safety concerns with global TGF-β inhibition. In this work, we reveal a novel mechanism of inhibiting TGF-β activation utilized by an αvβ8 targeting antibody, 37E1B5...
November 11, 2016: MAbs
Almudena Val-Blasco, Patricia Prieto-Chinchilla, Silvia Gonzalez-Ramos, Gemma Benito, María Teresa Vallejo-Cremades, Ivette Pacheco, María Pilar González-Peramato, Noelia Agra, Verónica Terrón, Carmen Delgado, Paloma Martín-Sanz, Lisardo Boscá, María Fernández-Velasco
Cardiac fibrosis and chronic inflammation are common complications in type 2 diabetes mellitus (T2D). Since nucleotide oligomerization-binding domain 1 (NOD1), an innate immune receptor, is involved in the pathogenesis of insulin resistance and diabetes outcomes, we sought to investigate its involvement in cardiac fibrosis. Here we show that selective staining of cardiac fibroblasts from T2D ( db/db;db ) mice exhibit up-regulation and activation of the NOD1 pathway, resulting in enhanced NF-kB and TGF-β signalling...
November 1, 2016: Biochemical Journal
Marcelina Koćwin, Mateusz Jonakowski, Marcelina Przemęcka, Jan Zioło, Michał Panek, Piotr Kuna
Asthma is a chronic inflammatory heterogeneous disease of the lower respiratory tract characterised by the occurrence of bronchial hyper-responsiveness and paroxysmal, changeable bronchial obstruction. Transforming growth factor-beta (TGF-b) is one of the cytokines involved in mediating airway inflammation and remodelling. The level of TGF-b1 gene expression correlates with severity of symptoms. Alterations in the main SMAD signal transmission, overexpression of TGF-b genes and changes in the transcriptome cause excessive secretion of TGF-b and its increased expression in target cells, which clinically induces a moderate-severe or severe course of asthma as well as an earlier and faster disease progression...
2016: Pneumonologia i Alergologia Polska
Yusuke Sugama, Hiroyuki Kuroda, Hiroto Horiguchi, Natsumi Yamauchi, Ken Sato, Michiko Yamada, Kohta Hamaguchi, Hajime Nakamura, Tomoyuki Abe, Shigeyuki Fujii, Masahiro Maeda, Miri Fujita, Masato Koguma, Tetsuhiko Koguma, Junji Kato
An 80-year-old man received a diagnosis of anemia and a decreased platelet count from his physician in 2008, and was referred to our department where primary myelofibrosis was diagnosed.The patient was classified into the lower risk group according to the International Prognostic Scoring System(IPSS), and was followed up without treatment.In June 2010, pancytopenia progressed, and the patient was reclassified into the higher risk group.Blood count did not increase with metenolone treatment, but increased with zoledronic acid(ZA)that he started receiving from January 2012...
September 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Ozgur Turk, Bartu Badak, Ersin Ates, Emine Dundar, Emine Sutken
In this study, we investigated the affect and the role of growth factors on liver damage. 110 Sprague-Dawley rats were divided into 11 groups: a sham group, a control group, HGF, EGF, IGF, TGF groups of irreversible jaundiced rats and a control group and HGF, EGF, IGF, and TGF groups of reversible jaundiced rats (n = 10). In the irreversible jaundiced groups, the common bile duct was explorated, double ligated, and cut. 150 μg/kg/day HGF, 5 μg/kg/day EGF, 5 μg/kg/day IGF, and 5 μg/kg/day TGF β-1 were injected intraperitoneally after the seventh post-operative day...
2016: SpringerPlus
Norelia Torrealba, Gonzalo Rodríguez-Berriguete, Benito Fraile, Gabriel Olmedilla, Pilar Martínez-Onsurbe, Manuel Guil-Cid, Ricardo Paniagua, Mar Royuela
BACKGROUND: This work is focused on finding new markers that complement or diagnoses currently used towards improving knowledge histological and statistical aspects that allow us to predict the local stage carcinomas and to identify and understand all the factors related to the progression of this disease. MATERIALS AND METHODS: Prostates were obtained from: normal prostates from 20 men, diagnosis of BPH (Benign Prostatic Hyperplasia) from 35 men and prostate cancer from 86 men...
August 12, 2016: Cytokine
S Patschan, D Tampe, C Müller, C Seitz, C Herink, G A Müller, E Zeisberg, M Zeisberg, E Henze, D Patschan
BACKGROUND: Patients with systemic sclerosis (SSc) are endagered by tissue fibrosis and by microvasculopathy, with the latter caused by endothelial cell expansion/proliferation. SSc-associated fibrosis potentially results from mesenchymal transdifferentiation of endothelial cells. Early Endothelial Progenitor Cells (eEPCs) act proangiogenic under diverse conditions. Aim of the study was to analyze eEPC regeneration and mesenchymal transdifferentiation in patients with limited and diffuse SSs (lSSc and dSSc)...
2016: BMC Musculoskeletal Disorders
Yakun Wu, Zheng Yu, Junhua Gong, Min Li, Yiming Liu, Jianping Gong
UNLABELLED:  Background and rationale for the study. Previous studies showed that CTLA4Ig and indoleamine 2,3-dioxygenase (IDO) genes played regulatory role in organ transplantation but failed to reach satisfactory effects. In this study, we constructed an adenovirus- mediated gene expressing CTLA4Ig-IDO and established rat liver transplantation models. Recipients were randomly divided into four groups of 10 rats each. During the operation, CTLA4Ig, IDO, and CTLA4Ig-IDO genes, as well as a blank plasmid, were infused into different rat groups via portal vein to determine their effects on inducing immune tolerance...
September 2016: Annals of Hepatology
Wenjie Wang, Judong Luo, Wenjiong Sheng, Jiao Xue, Ming Li, Jiang Ji, Pengfei Liu, Xueguang Zhang, Jianping Cao, Shuyu Zhang
PURPOSE: To investigate the molecular changes underlying the pathogenesis of radiation-induced skin fibrosis. METHODS AND MATERIALS: Rat skin was irradiated to 30 or 45 Gy with an electron beam. Protein expression in fibrotic rat skin and adjacent normal tissues was quantified by label-free protein quantitation. Human skin cells HaCaT and WS-1 were treated by x-ray irradiation, and the proteasome activity was determined with a fluorescent probe. The effect of proteasome inhibitors on Transforming growth factor Beta (TGF-B) signaling was measured by Western blot and immunofluorescence...
June 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Tamami Nakamura, Tohru Hosoyama, Daichi Kawamura, Yuriko Takeuchi, Yuya Tanaka, Makoto Samura, Koji Ueno, Arata Nishimoto, Hiroshi Kurazumi, Ryo Suzuki, Hiroshi Ito, Kensuke Sakata, Akihito Mikamo, Tao-Sheng Li, Kimikazu Hamano
Advanced age affects various tissue-specific stem cells and decreases their regenerative ability. We therefore examined whether aging affected the quantity and quality of cardiac stem cells using cells obtained from 26 patients of various ages (from 2 to 83 years old). We collected fresh right atria and cultured cardiosphere-derived cells (CDCs), which are a type of cardiac stem cell. Then we investigated growth rate, senescence, DNA damage, and the growth factor production of CDCs. All samples yielded a sufficient number of CDCs for experiments and the cellular growth rate was not obviously associated with age...
2016: Scientific Reports
Chunyou Wang, Pian Liu, Heshui Wu, Pengfei Cui, Yongfeng Li, Yao Liu, Zhiqiang Liu, Shanmiao Gou
Pancreatic ductal adenocarcinoma (PDAC), which accounts for 96% of all pancreatic cancer cases, is characterized by rapid progression, invasion and metastasis. Transforming growth factor-beta (TGF-β) signaling is an essential pathway in metastatic progression and microRNAs (miRNA) play central roles in the regulation of various biological and pathologic processes including cancer metastasis. However, the molecular mechanisms involved in regulation of miRNAs and activation of TGF-β signaling in PDAC remain to be established...
March 22, 2016: Oncotarget
Bader Al-Saikan, Jie Ding, Edward Tredget, Peter Metcalfe
INTRODUCTION: Partial bladder outlet obstruction (pBOO) results in significant morbidity and mortality in the pediatric and adult populations. Mesenchymal stem cells (MSC) have been widely studied in many organ systems for the treatment and prevention of fibrotic and inflammatory conditions. Therefore, we hypothesize that systemic administration of MSC will demonstrate short-term biochemical, histological, and urodynamic benefits in an animal model for pBOO. METHODS: After University ethics approval, 5 × 106 green fluorescent protein GFP-labeled MSC were intravenously injected concurrently with pBOO in adult Sprague-Dawley rats...
January 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
V W W Tsai, S Lin, D A Brown, A Salis, S N Breit
Anorexia-cachexia associated with cancer and other diseases is a common and often fatal condition representing a large area of unmet medical need. It occurs most commonly in advanced cancer and is probably a consequence of molecules released by tumour cells, or tumour-associated interstitial or immune cells. These may then act directly on muscle to cause atrophy and/or may cause anorexia, which then leads to loss of both fat and lean mass. Although the aetiological triggers for this syndrome are not well characterized, recent data suggest that MIC-1/GDF15, a transforming growth factor-beta superfamily cytokine produced in large amounts by cancer cells and as a part of other disease processes, may be an important trigger...
February 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Justyna Kiszałkiewicz, Wojciech J Piotrowski, Ewa Brzeziańska-Lasota
Sarcoidosis is an orphan inflammatory disorder that can virtually affect any organ or system in the body, although the lungs and lymph nodes are most frequently involved. Sarcoidosis is believed to derive from an interaction between environmental and genetic agents. Many studies emphasize a strong association between certain human leukocyte antigen (HLA) alleles and sarcoidosis susceptibility. Several new insights have allowed the further evaluation of other candidate genes with a potential function in the immunopathogenesis of sarcoidosis...
2015: Pneumonologia i Alergologia Polska
Lindsay R Stolzenburg, Sarah Wachtel, Hong Dang, Ann Harris
Irreversible respiratory obstruction resulting from progressive airway damage, inflammation and fibrosis is a feature of several chronic respiratory diseases, including cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). The cytokine transforming growth factor β (TGF-β) has a pivotal role in promoting lung fibrosis and is implicated in respiratory disease severity. In the present study, we show that a previously uncharacterized miRNA, miR-1343, reduces the expression of both TGF-β receptor 1 and 2 by directly targeting their 3'-UTRs...
February 1, 2016: Biochemical Journal
Guan Fook Ng, Ishak Siti Raihan, Yaakub Azhany, Che Hussin Che Maraina, K Gurusamy Banumathi, Tajudin Liza-Sharmini
PURPOSE: To compare the levels of conjunctival transforming growth factor beta (TGF-β) between glaucoma and control patients and to determine conjunctival TGF-β levels before and 3 months after augmented primary trabeculectomy. METHODS: Patients with primary open angle glaucoma (POAG) or primary angle closure glaucoma (PACG) admitted for mitomycin (MMC) augmented primary trabeculectomy due to failure in achieving target pressure after maximum medical therapy were selected...
2015: Open Ophthalmology Journal
Nathan W Bronson, Brian S Diggs, Gene Bakis, Kenneth M Gatter, Brett C Sheppard, John G Hunter, James P Dolan
A reliable method to identify pathologic complete responders (pCR) or non-responders (NR) to neoadjuvant chemoradiation therapy (NAT) would dramatically improve therapy for esophageal cancer. The purpose of this study is to investigate if a distinct profile of prognostic molecular markers can predict pCR after neoadjuvant therapy. Expression of p53, Her-2/neu, Cox-2, Beta-catenin, E-cadherin, MMP-1, NFkB, and TGF-B was measured by immunohistochemistry in pre-treatment biopsy tissue and graded by an experienced pathologist...
December 2015: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
R G Ahmed, M Abdel-Latif, Emad A Mahdi, Khalid A El-Nesr
The potentiation of the immune system in pregnant rats was performed with Complete Freund's Adjuvant [CFA; 20μl, subcutaneous at gestation day (GD) 18] in experimentally-induced hyperthyroidism by Levo-thyroxine (L-T4; 10μg/100g of b.w., intraperitoneal from GD 2 to 17). The potential effects on the fetal neuroendocrine function were evaluated by observing some histopathological investigations in pregnant rats and measuring some biochemical parameters in dams and their fetuses at GD 20. In hyperthyroid group, an increase in maternofetal serum thyroxine (T4), triiodothyronine (T3) and a decrease in thyrotropin (TSH) levels were noticed, while the concentrations of fetal serum growth hormone (GH) and insulin-like growth factor-1 (IGF1) levels were increased at tested GD with respect to control and CFA groups...
December 2015: International Immunopharmacology
Rajiv D Machado, Laura Southgate, Christina A Eichstaedt, Micheala A Aldred, Eric D Austin, D Hunter Best, Wendy K Chung, Nicola Benjamin, C Gregory Elliott, Mélanie Eyries, Christine Fischer, Stefan Gräf, Katrin Hinderhofer, Marc Humbert, Steven B Keiles, James E Loyd, Nicholas W Morrell, John H Newman, Florent Soubrier, Richard C Trembath, Rebecca Rodríguez Viales, Ekkehard Grünig
Pulmonary arterial hypertension (PAH) is an often fatal disorder resulting from several causes including heterogeneous genetic defects. While mutations in the bone morphogenetic protein receptor type II (BMPR2) gene are the single most common causal factor for hereditary cases, pathogenic mutations have been observed in approximately 25% of idiopathic PAH patients without a prior family history of disease. Additional defects of the transforming growth factor beta pathway have been implicated in disease pathogenesis...
December 2015: Human Mutation
Lena Ho, Shawn Y X Tan, Sheena Wee, Yixuan Wu, Sam J C Tan, Navin B Ramakrishna, Serene C Chng, Srikanth Nama, Iwona Szczerbinska, Iwona Sczerbinska, Yun-Shen Chan, Stuart Avery, Norihiro Tsuneyoshi, Huck Hui Ng, Jayantha Gunaratne, N Ray Dunn, Bruno Reversade
ELABELA (ELA) is a peptide hormone required for heart development that signals via the Apelin Receptor (APLNR, APJ). ELA is also abundantly secreted by human embryonic stem cells (hESCs), which do not express APLNR. Here we show that ELA signals in a paracrine fashion in hESCs to maintain self-renewal. ELA inhibition by CRISPR/Cas9-mediated deletion, shRNA, or neutralizing antibodies causes reduced hESC growth, cell death, and loss of pluripotency. Global phosphoproteomic and transcriptomic analyses of ELA-pulsed hESCs show that it activates PI3K/AKT/mTORC1 signaling required for cell survival...
October 1, 2015: Cell Stem Cell
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