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Bleomycin pulmonary fibrosis

Xingjian Liu, Shuren Ma, Gerard Turino, Jerome Cantor
INTRODUCTION: Desmosine and isodesmosine (DID) are unique elastin crosslinks that may serve as biomarkers for elastic fiber degradation in chronic obstructive pulmonary disease. Previously, our laboratory found that the ratio of free to peptide-bound DID in bronchoalveolar lavage fluid (BALF) showed a significant positive correlation with the extent of airspace enlargement in an elastase model of pulmonary emphysema. To further evaluate this hypothesis, our laboratory measured this ratio in a bleomycin (BLM) model of pulmonary fibrosis, which involved different microarchitectural changes than those associated with pulmonary emphysema...
October 19, 2016: Lung
Ankit Mangla, Nikki Agarwal, Chou Carmel, Thomas Lad
Erlotinib is one of the most widely used tyrosine kinase inhibitor targeting human epidermal growth factor receptor. Since its introduction, it has revolutionized the treatment of advanced non-small cell lung cancer. Skin rashes and diarrhea are the most often reported side effects of erlotinib however it is also associated with interstitial pneumonitis or interstitial lung disease, which often turns out to be fatal complication of using this medicine. Though reported scarcely in the western world, the association of interstitial lung disease with epidermal growth factor receptor has attracted a lot of attention in the recent times...
September 5, 2016: Rare Tumors
Mariola Kurowska-Stolarska, Manhl K Hasoo, David J Welsh, Lynn Stewart, Donna McIntyre, Brian E Morton, Steven Johnstone, Ashley M Miller, Darren L Asquith, Neal L Millar, Ann B Millar, Carol A Feghali-Bostwick, Nikhil Hirani, Peter J Crick, Yuqin Wang, William J Griffiths, Iain B McInnes, Charles McSharry
BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is progressive and rapidly fatal. Improved understanding of pathogenesis is required to prosper novel therapeutics. Epigenetic changes contribute to IPF therefore microRNAs may reveal novel pathogenic pathways. OBJECTIVES: To determine the regulatory role of microRNA(miR)-155 in the pro-fibrotic function of murine lung macrophages and fibroblasts, IPF lung fibroblasts and its contribution to experimental pulmonary fibrosis...
October 13, 2016: Journal of Allergy and Clinical Immunology
Argyrios Tzouvelekis, Guoying Yu, Christian Lacks Lino Cardenas, Jose D Herazo-Maya, Rong Wang, Tony Woolard, Yi Zhang, Koji Sakamoto, Hojin Lee, Jae-Sung Yi, Giuseppe DeIuliis, Nikolaos Xylourgidis, Farida Ahangari, Patty J Lee, Vassilis Aidinis, Erica L Herzog, Robert Homer, Anton M Bennett, Naftali Kaminski
RATIONALE: Idiopathic Pulmonary Fibrosis (IPF) is a chronic fatal lung disease with dismal prognosis and no cure. The potential role of the ubiquitously expressed SH2 domain-containing-tyrosine phosphatase (SHP2) as a therapeutic target has not been studied in IPF Objectives: To determine the expression, mechanistic role and potential therapeutic utility of SHP2 in Pulmonary Fibrosis Methods: The effects of SHP2 overexpression and inhibition on fibroblast response to pro-fibrotic stimuli were analyzed in-vitro in primary human and mouse lung fibroblasts...
October 13, 2016: American Journal of Respiratory and Critical Care Medicine
Ruijuan Guan, Xiaomei Zhao, Xia Wang, Nana Song, Yuhong Guo, Xianxia Yan, Liping Jiang, Wenjing Cheng, Linlin Shen
Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease with few treatment options and poor prognosis. Emodin, extracted from Chinese rhubarb, was found to be able to alleviate bleomycin (BLM)-induced pulmonary fibrosis, yet the underlying mechanism remains largely unknown. This study aimed to further investigate the effects of emodin on the inflammation and fibrosis of BLM-induced pulmonary fibrosis and the mechanism involved in rats. Our results showed that emodin improved pulmonary function, reduced weight loss and prevented death in BLM-treated rats...
October 4, 2016: Toxicology Letters
Laura Lucarini, Mariaconcetta Durante, Cecilia Lanzi, Alessandro Pini, Giulia Boccalini, Laura Calosi, Flavio Moroni, Emanuela Masini, Guido Mannaioni
Idiopathic pulmonary fibrosis is a severe disease characterized by excessive myofibroblast proliferation, extracellular matrix and fibrils deposition, remodelling of lung parenchyma and pulmonary insufficiency. Drugs able to reduce disease progression are available, but therapeutic results are unsatisfactory; new and safe treatments are urgently needed. Poly(ADP-ribose) polymerases-1 (PARP-1) is an abundant nuclear enzyme involved in key biological processes: DNA repair, gene expression control, and cell survival or death...
October 4, 2016: Journal of Cellular and Molecular Medicine
Samah M Elaidy, Soha S Essawy
BACKGROUND: The most widespread chronic fibrosing lung disease is idiopathic pulmonary fibrosis. Lung serotonin (5-HT) content is increased during pulmonary fibrosis with the implication of 5-HT2 receptors in the pathogenesis. Serotonin plays important roles in alveolar macrophages function through 5-HT2C receptors activation. Numerous studies described the important role of 5-HT2A/B receptor blockers in suppressing different types of fibrosis as idiopathic pulmonary fibrosis. The current study pointed to examine the antifibrotic effects of RS-102221 and/or terguride through in vivo model of pulmonary fibrosis...
August 12, 2016: Pharmacological Reports: PR
Adilson Santos Andrade-Sousa, Paulo Rogério Pereira, BreAnne MacKenzie, Manoel Carneiro Oliveira-Junior, Erasmo Assumpção-Neto, Maysa Alves Rodrigues Brandão-Rangel, Nilsa Regina Damaceno-Rodrigues, Elia Garcia Caldini, Ana Paula Pereira Velosa, Walcy Rosolia Teodoro, Ana Paula Ligeiro de Oliveira, Marisa Dolhnikoff, Oliver Eickelberg, Rodolfo Paula Vieira
INTRODUCTION: The aim of this study was to investigate the effect of aerobic exercise (AE) in reducing bleomycin-induced fibrosis in mice of a Th2-dominant immune background (BALB/c). METHODS: BALB/c mice were distributed into: sedentary, control (CON), Exercise-only (EX), sedentary, bleomycin-treated (BLEO) and bleomycin-treated+exercised (BLEO+EX); (n = 8/group). Following treadmill adaptation, 15 days following a single, oro-tracheal administration of bleomycin (1...
2016: PloS One
Jin Tao, Qinglun Li, Xiaowei Ma, Fei Han, Xiaoming Liu, Jun Wei, Yongzhao Zhu
Objective To investigate the therapeutic effect and mechanism of human placental mesenchymal stem cells of fetal origin (hfPMSCs) cultured in serum-free medium on mouse pulmonary fibrosis induced by bleomycin treatment. Methods Human hfPMSCs were cultured and identified by flow cytometry. Fifteen 6-week-old male SPF C57BL/6J mice were divided into 3 groups: bleomycin treatment group, hfPMSCs transplantation group and negative control group. Pulmonary fibrosis model was induced in the mice of bleomycin treatment group and hfPMSCs transplantation group with bleomycin (1 μg/L, 50 μL) via intratracheal instillation...
October 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Lijing Liu, Hong Qian, Hua Xiao, Jianbin He, Maofeng Xie, Zaiyan Wang, Xingyun Long
Objective To explore the role of transforming growth factor-β1 (TGF-β1)/a disintegrin-like and metalloproteinase with thrombospondin type 1 motif (ADAMTS-1) signaling pathway in emodin's anti-pulmonary fibrosis. Methods Sixty SD rats were randomly divided into 6 groups: normal control group, sham-operated group, model group, low-dose emodin intervention group (20 mg/kg), high-dose emodin intervention group (80 mg/kg) and prednisone group (5 mg/kg). Each group included 10 animals. Rats in the latter 4 groups were intratracheally injected with bleomycin A5 to induce pulmonary fibrosis, whereas bleomycin A5 was replaced by normal saline in sham-operated group...
October 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Xiaoying Huang, Yicheng He, Yanfan Chen, Peiliang Wu, Di Gui, Hui Cai, Ali Chen, Mayun Chen, Caijun Dai, Dan Yao, Liangxing Wang
BACKGROUND: Baicalin has been reported to have anti-fibrosis effect; however, its mechanism still remains to be elucidated. Adenosine A2a receptor (A2aR) is a novel inflammation regulator, and transforming growth factor-β1 (TGF-β1)-induced extracellular signal regulated kinase1/2 (ERK1/2) signaling pathway plays an important role in idiopathic pulmonary fibrosis (IPF). This study was to explore the relationship of A2aR and TGF-β1-induced ERK1/2 in bleomycin (BLM)-induced pulmonary fibrosis in mice, and to investigate whether A2aR mediate the anti-fibrosis effect of Baicalin on BLM-induced pulmonary fibrosis...
2016: BMC Pulmonary Medicine
Christine L Vigeland, Samuel L Collins, Yee Chan-Li, Andrew H Hughes, Min-Hee Oh, Jonathan D Powell, Maureen R Horton
Pulmonary fibrosis is a devastating, incurable disease in which chronic inflammation and dysregulated, excessive wound healing lead to progressive fibrosis, lung dysfunction, and ultimately death. Prior studies have implicated the cytokine IL-17A and Th17 cells in promoting the development of fibrosis. We hypothesized that loss of Th17 cells via CD4-specific deletion of mTORC1 activity would abrogate the development of bleomycin-induced pulmonary fibrosis. However, in actuality loss of Th17 cells led to increased mortality and fibrosis in response to bleomycin...
2016: PloS One
Rajkumar Venkatadri, Anand Krishnan V Iyer, Vani Ramesh, Clayton Wright, Carlos A Castro, Juan S Yakisich, Neelam Azad
Cellular oxidative stress is implicated not only in lung injury but also in contributing to the development of pulmonary fibrosis. We demonstrate that a cell-permeable superoxide dismutase (SOD) mimetic and peroxynitrite scavenger, manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) significantly inhibited bleomycin-induced fibrogenic effects both in vitro and in vivo. Further investigation into the underlying mechanisms revealed that MnTBAP targets canonical Wnt and non-canonical Wnt/Ca2+ signaling pathways, both of which were upregulated by bleomycin treatment...
September 20, 2016: Journal of Cellular Physiology
Xin Geng, Kobina Dufu, Athiwat Hutchaleelaha, Qing Xu, Zhe Li, Chien-Ming Li, Mira P Patel, Nicholas Vlahakis, Josh Lehrer-Graiwer, Donna Oksenberg
Although exertional dyspnea and worsening hypoxia are hallmark clinical features of idiopathic pulmonary fibrosis (IPF), no drug currently available could treat them. GBT1118 is a novel orally bioavailable small molecule that binds to hemoglobin and produces a concentration-dependent left shift of the oxygen-hemoglobin dissociation curve with subsequent increase in hemoglobin-oxygen affinity and arterial oxygen loading. To assess whether pharmacological modification of hemoglobin-oxygen affinity could ameliorate hypoxemia associated with lung fibrosis, we evaluated GBT1118 in a bleomycin-induced mouse model of hypoxemia and fibrosis...
September 2016: Physiological Reports
Yongjun Tang, Ruoxi He, Jian An, Pengbo Deng, Li Huang, Wei Yang
Pulmonary fibrosis, characterized by the destruction of lung tissue architecture and the formation of fibrous foci, currently has no satisfactory treatment. Emodin is a component of Chinese herb that has been reported to be medicable on pancreatic fibrosis and liver fibrosis. However, its role in pulmonary fibrosis has not been reported yet. In the present study, we investigated the hypothesis that H19 play a promotive role in bleomycin-induced epithelial-mesenchymal transition of alveolar epithelial cell, and H19 exerts its effect through miR-29b regulation...
October 21, 2016: Biochemical and Biophysical Research Communications
Xueyan Peng, Meagan Moore, Aditi Mathur, Yang Zhou, Huanxing Sun, Ye Gan, Jose D Herazo-Maya, Naftali Kaminski, Xinyuan Hu, Hongyi Pan, Changwan Ryu, Awo Osafo-Addo, Robert J Homer, Carol Feghali-Bostwick, Wassim Fares, Mridu Gulati, Buqu Hu, Chun-Geun Lee, Jack A Elias, Erica L Herzog
Pulmonary fibrosis is a progressive and often fatal condition that is believed to be partially orchestrated by macrophages. Mechanisms that control migration of these cells into and within the lung remain undefined. We evaluated the contributions of the semaphorin receptor, plexin C1 (PLXNC1), and the exocytic calcium sensor, synaptotagmin 7 (Syt7), in these processes. We evaluated the role of PLXNC1 in macrophage migration by using Boyden chambers and scratch tests, characterized its contribution to experimentally induced lung fibrosis in mice, and defined the mechanism for our observations...
September 8, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Ling Nan, Anastasia M Jacko, Jiangning Tan, Dan Wang, Jing Zhao, Daniel J Kass, Haichun Ma, Yutong Zhao
Transforming growth factor β-1 (TGFβ-1)-induced phosphorylation of transcription factors Smad2 and Smad3 plays a crucial role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, the molecular regulation of Smad2/Smad3 proteins stability remains a mystery. Here, we show that ubiquitin carboxyl-terminal hydrolase-L5 (UCHL5 or UCH37) de-ubiquitinates both Smad2 and Smad3, up-regulates their stability, and promotes TGFβ-1-induced expression of profibrotic proteins, such as fibronectin (FN) and α-smooth muscle actin (α-SMA)...
2016: Scientific Reports
Tomonori Makiguchi, Mitsuhiro Yamada, Yusuke Yoshioka, Hisatoshi Sugiura, Akira Koarai, Shigeki Chiba, Naoya Fujino, Yutaka Tojo, Chiharu Ota, Hiroshi Kubo, Seiichi Kobayashi, Masaru Yanai, Sanae Shimura, Takahiro Ochiya, Masakazu Ichinose
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis. Although the median survival is 3 years, the clinical course varies to a large extent among IPF patients. To date, there has been no definitive prognostic marker. Extracellular vesicles (EVs) are known to hold nucleic acid, including microRNAs, and to regulate gene expression in the recipient cells. Moreover, EVs have been shown to express distinct surface proteins or enveloped microRNAs depending on the parent cell or pathological condition...
2016: Respiratory Research
Xiao Xiao, Lakmini K Senavirathna, Xuxu Gou, Chaoqun Huang, Yurong Liang, Lin Liu
The accumulation of fibroblasts/myofibroblasts in fibrotic foci is one of the characteristics of idiopathic pulmonary fibrosis (IPF). Enhancer of zeste homolog 2 (EZH2) is the catalytic component of a multiprotein complex, polycomb repressive complex 2, which is involved in the trimethylation of histone H3 at lysine 27. In this study, we investigated the role and mechanisms of EZH2 in the differentiation of fibroblasts into myofibroblasts. We found that EZH2 was upregulated in the lungs of patients with IPF and in mice with bleomycin-induced lung fibrosis...
September 2016: Physiological Reports
Nahoko Sato, Naoki Takasaka, Masahiro Yoshida, Kazuya Tsubouchi, Shunsuke Minagawa, Jun Araya, Nayuta Saito, Yu Fujita, Yusuke Kurita, Kenji Kobayashi, Saburo Ito, Hiromichi Hara, Tsukasa Kadota, Haruhiko Yanagisawa, Mitsuo Hashimoto, Hirofumi Utsumi, Hiroshi Wakui, Jun Kojima, Takanori Numata, Yumi Kaneko, Makoto Odaka, Toshiaki Morikawa, Katsutoshi Nakayama, Hirotsugu Kohrogi, Kazuyoshi Kuwano
BACKGROUND: Accumulation of profibrotic myofibroblasts in fibroblastic foci (FF) is a crucial process for development of fibrosis during idiopathic pulmonary fibrosis (IPF) pathogenesis, and transforming growth factor (TGF)-β plays a key regulatory role in myofibroblast differentiation. Reactive oxygen species (ROS) has been proposed to be involved in the mechanism for TGF-β-induced myofibroblast differentiation. Metformin is a biguanide antidiabetic medication and its pharmacological action is mediated through the activation of AMP-activated protein kinase (AMPK), which regulates not only energy homeostasis but also stress responses, including ROS...
2016: Respiratory Research
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