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Bleomycin pulmonary fibrosis

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https://www.readbyqxmd.com/read/28821136/discovery-of-enzymatically-depolymerized-heparins-capable-of-treating-bleomycin-induced-pulmonary-injury-and-fibrosis-in-mice
#1
Yishu Yan, Shanshan Du, Yang Ji, Nan Su, Yi Wang, Xiang Mei, Wenming Zhu, Dong He, Yuan Lu, Chong Zhang, Xin-Hui Xing
Heparin has recently been shown to slow down idiopathic pulmonary fibrosis (IPF) process and improve survival of patients in some cases. To improve the anti-IPF function while minimizing their side effects, we developed heparin libraries with different structures depolymerized by single or combined heparinases, and systematically screened the efficacy of the different heparins for treatment of Bleomycin-induced pulmonary injury and fibrosis using mice model. Then we characterized the structural properties of the components capable of treating pulmonary injury and fibrosis by use of chip-based amide hydrophilic interaction chromatography (HILIC)-fourier transform (FT)-ESI-MS, polyacrylamide gel electrophoresis (PAGE), and high performance liquid chromatography (HPLC)...
October 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28820502/oligonucleotides-targeting-periostin-ameliorates-pulmonary-fibrosis
#2
A Tomaru, T Kobayashi, J A Hinneh, P B Tonto, C N D' Alessandro-Gabazza, H Fujimoto, K Fujiwara, Y Takahashi, M Ohnishi, T Yasuma, K Nishihama, M Yoshino, K Takao, M Toda, T Totoki, Y Takei, K Yoshikawa, O Taguchi, E C Gabazza
Idiopathic pulmonary fibrosis (IPF) is a fatal disease with a median survival of 3 to 4 years after diagnosis. It is the most frequent form of a group of interstitial pneumonias of unknown etiology. Current available therapies prevent deterioration of lung function but no therapy has shown to improve survival. Periostin is a matricellular protein of the fasciclin 1 family. There is increased deposition of periostin in lung fibrotic tissues. Here, we evaluated whether small interfering RNA or antisense oligonucleotide against periostin inhibit lung fibrosis by direct administration into the lung by intranasal route...
August 18, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28817691/rac2-is-required-for-alternative-macrophage-activation-and-bleomycin-induced-pulmonary-fibrosis-a-macrophage-autonomous-phenotype
#3
Shweta Joshi, Alok R Singh, Simon S Wong, Muamera Zulcic, Min Jiang, Annie Pardo, Moises Selman, James S Hagood, Donald L Durden
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by cellular phenotype alterations and deposition of extracellular matrix proteins. The alternative activation of macrophages in the lungs has been associated as a major factor promoting pulmonary fibrosis, however the mechanisms underlying this phenomenon are poorly understood. In the present study, we have defined a molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin lead to the activation of Rac2 which regulates alternative macrophage differentiation, a signaling axis within the pulmonary macrophage compartment required for bleomycin induced pulmonary fibrosis...
2017: PloS One
https://www.readbyqxmd.com/read/28816543/mir-541-5p-regulates-lung-fibrosis-by-targeting-cyclic-nucleotide-phosphodiesterase-1a
#4
Liqin Ren, Chunyan Yang, Yongfeng Dou, Renhui Zhan, Yi Sun, Yan Yu
AIM OF THE STUDY: Idiopathic pulmonary fibrosis (IPF) is a lethal human disease with short survival time and few treatment options. In this study, we aim to demonstrate that cyclic nucleotide phosphodiesterase 1A (PDE1A), a Ca2+/calmodulin-stimulating PDE family member, plays a critical role in the induction of fibrosis and angiogenesis in the lung. MATERIALS AND METHODS: To induce pulmonary damage, adult male SD rats were treated with bleomycin in a dose of 6 mg/kg body weight by a single intratracheal instillation...
August 17, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28816009/protective-effect-of-atazanavir-sulfate-against-pulmonary-fibrosis-in-vivo-and-in-vitro
#5
Shina Song, Yunxia Ji, Guanghua Zhang, Xue Zhang, Bin Li, Defang Li, Wanglin Jiang
Atazanavir sulfate, an antiretroviral protease inhibitor, has been used to treat HIV/AIDS, but its ability to serve as an anti-pulmonary fibrosis (PF) agent remains unknown. In this study, the effects of atazanavir sulfate on various aspects of PF were examined and CoCl2 was used to induce the hypoxia-mimicking condition in vitro, including epithelial-mesenchymal transition (EMT) in A549 cells, endothelial-mesenchymal transition (EndMT) in human pulmonary microvascular endothelial cells (HPMECs), proliferation in human lung fibroblasts (HLF-1) and potential protective effects in human type I alveolar epithelial cells (AT I)...
August 16, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28814671/antifibrotic-role-of-vascular-endothelial-growth-factor-in-pulmonary-fibrosis
#6
Lynne A Murray, David M Habiel, Miriam Hohmann, Ana Camelo, Huilan Shang, Yang Zhou, Ana Lucia Coelho, Xueyan Peng, Mridu Gulati, Bruno Crestani, Matthew A Sleeman, Tomas Mustelin, Meagan W Moore, Changwan Ryu, Awo D Osafo-Addo, Jack A Elias, Chun G Lee, Buqu Hu, Jose D Herazo-Maya, Darryl A Knight, Cory M Hogaboam, Erica L Herzog
The chronic progressive decline in lung function observed in idiopathic pulmonary fibrosis (IPF) appears to result from persistent nonresolving injury to the epithelium, impaired restitution of the epithelial barrier in the lung, and enhanced fibroblast activation. Thus, understanding these key mechanisms and pathways modulating both is essential to greater understanding of IPF pathogenesis. We examined the association of VEGF with the IPF disease state and preclinical models in vivo and in vitro. Tissue and circulating levels of VEGF were significantly reduced in patients with IPF, particularly in those with a rapidly progressive phenotype, compared with healthy controls...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28811360/involvement-of-midkine-in-the-development-of-pulmonary-fibrosis
#7
Kenichi Misa, Yoshinori Tanino, Xintao Wang, Takefumi Nikaido, Masami Kikuchi, Yuki Sato, Ryuichi Togawa, Mishie Tanino, Shinya Tanaka, Kenji Kadomatsu, Mitsuru Munakata
Midkine is a low-molecular-weight heparin-binding protein that is strongly expressed mainly in the midgestation period and has various physiological activities such as in development and cell migration. Midkine has been reported to be strongly expressed in cancer cells and in inflammation and repair processes, and to be involved in the pathogenesis of various diseases. However, its role in the lung is poorly understood. In this study, we analyzed the clinical characteristics of idiopathic pulmonary fibrosis patients in relation to midkine expression and used a mouse bleomycin-induced pulmonary fibrosis model to investigate the role of midkine in pulmonary fibrosis...
August 2017: Physiological Reports
https://www.readbyqxmd.com/read/28810065/olodaterol-shows-anti-fibrotic-efficacy-in-in-vitro-and-in-vivo-models-of-pulmonary-fibrosis
#8
Franziska Elena Herrmann, Lutz Wollin, Johannes Wirth, Florian Gantner, Bärbel Lämmle, Eva Wex
BACKGROUND AND PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease characterized by excessive fibroblast activation ultimately leading to scarring of the lungs. Although, the activation of β2 -adrenergic receptors (β2 -AR) has been shown to inhibit pro-fibrotic events primarily in cell lines, the role of β2 -AR agonism has not yet been fully characterized. The aim of our study was to explore the anti-fibrotic activity of the long-acting β2 -AR-agonist olodaterol in primary human lung fibroblasts, and in murine models of pulmonary fibrosis...
August 15, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28804709/exploring-animal-models-that-resemble-idiopathic-pulmonary-fibrosis
#9
REVIEW
Jun Tashiro, Gustavo A Rubio, Andrew H Limper, Kurt Williams, Sharon J Elliot, Ioanna Ninou, Vassilis Aidinis, Argyrios Tzouvelekis, Marilyn K Glassberg
Large multicenter clinical trials have led to two recently approved drugs for patients with idiopathic pulmonary fibrosis (IPF); yet, both of these therapies only slow disease progression and do not provide a definitive cure. Traditionally, preclinical trials have utilized mouse models of bleomycin (BLM)-induced pulmonary fibrosis-though several limitations prevent direct translation to human IPF. Spontaneous pulmonary fibrosis occurs in other animal species, including dogs, horses, donkeys, and cats. While the fibrotic lungs of these animals share many characteristics with lungs of patients with IPF, current veterinary classifications of fibrotic lung disease are not entirely equivalent...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28801346/pan-ppar-agonist-iva337-is-effective-in-experimental-lung-fibrosis-and-pulmonary-hypertension
#10
Jerome Avouac, Irena Konstantinova, Christophe Guignabert, Sonia Pezet, Jeremy Sadoine, Thomas Guilbert, Anne Cauvet, Ly Tu, Jean-Michel Luccarini, Jean-Louis Junien, Pierre Broqua, Yannick Allanore
OBJECTIVE: To evaluate the antifibrotic effects of the pan-peroxisome proliferator-activated receptor (PPAR) agonist IVA337 in preclinical mouse models of pulmonary fibrosis and related pulmonary hypertension (PH). METHODS: IVA337 has been evaluated in the mouse model of bleomycin-induced pulmonary fibrosis and in Fra-2 transgenic mice, this latter being characterised by non-specific interstitial pneumonia and severe vascular remodelling of pulmonary arteries leading to PH...
August 11, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28800254/sirt1-protects-against-systemic-sclerosis-related-pulmonary-fibrosis-by-decreasing-pro-inflammatory-and-pro-fibrotic-processes
#11
Haiyan Chu, Shuai Jiang, Qingmei Liu, Yanyun Ma, Xiaoxia Zhu, Minrui Liang, Xiangguang Shi, Weifeng Ding, Xiaodong Zhou, Hejian Zou, Feng Qian, Philip W Shaul, Li Jin, Jiucun Wang
Pulmonary fibrosis is the leading cause of death in systemic sclerosis (SSc). Sirtuin1 (SIRT1) is a deacetylase with known anti-inflammatory and anti-fibrotic activity in the liver, kidney and skin. The role of SIRT1 in SSc-related pulmonary fibrosis is unknown. In the present work, we determined that the expression of SIRT1 in peripheral blood mononuclear cells of SSc patients with pulmonary fibrosis is lower than that in SSc patients without pulmonary fibrosis. In in vivo studies of Bleomycin-induced lung fibrosis in mice, SIRT1 activation with Resveratrol reduced collagen production when it was administered either prophylactically during the inflammatory stage or after the development of fibrosis...
August 11, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28798256/metabolic-characterization-and-rna-profiling-reveal-glycolytic-dependence-of-pro-fibrotic-phenotype-of-alveolar-macrophages-in-lung-fibrosis
#12
Na Xie, Huachun Cui, Jing Ge, Sami Banerjee, Sijia Guo, Shubham Dubey, Edward Abraham, Rui-Ming Liu, Gang Liu
Metabolic reprogramming has been intrinsically linked to macrophage activation. Alveolar macrophages are known to play an important role in the pathogenesis of pulmonary fibrosis. However, systematic characterization of expression profile in these cells is still lacking. Furthermore, main metabolic programs and their regulation of cellular phenotype are completely unknown. In this study, we comprehensively analyzed the expression profile and main metabolic programs in alveolar macrophages from mice with or without experimental pulmonary fibrosis...
August 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28783251/safety-and-efficacy-of-allogeneic-lung-spheroid-cells-in-a-mismatched-rat-model-of-pulmonary-fibrosis
#13
Jhon Cores, M Taylor Hensley, Kathryn Kinlaw, S Michaela Rikard, Phuong-Uyen Dinh, Dipti Paudel, Junnan Tang, Adam C Vandergriff, Tyler A Allen, Yazhou Li, Jianhua Liu, Bo Niu, Yuepeng Chi, Thomas Caranasos, Leonard J Lobo, Ke Cheng
Idiopathic pulmonary fibrosis is a devastating interstitial lung disease characterized by the relentless deposition of extracellular matrix causing lung distortions and dysfunctions. The prognosis after detection is merely 3-5 years and the only two Food and Drug Administration-approved drugs treat the symptoms, not the disease, and have numerous side effects. Stem cell therapy is a promising treatment strategy for pulmonary fibrosis. Current animal and clinical studies focus on the use of adipose or bone marrow-derived mesenchymal stem cells...
August 7, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28776666/potential-role-of-the-jagged1-notch1-signaling-pathway-in-the-endothelial-myofibroblast-transition-during-blm-induced-pulmonary-fibrosis
#14
Qian Yin, Weihua Wang, Guangbin Cui, Linfeng Yan, Song Zhang
Endothelial cell myofibroblast transition (EndoMT) is found during the process of bleomycin (BLM)-induced pulmonary fibrosis in rats, and plays a very important role in sustaining inflammation and collagen secretion. Moreover, some studies have suggested that the Notch1 signaling pathway may be involved in the expression of Î ± -smooth muscle actin (Î ± -SMA) in pulmonary microvascular endothelial cells (PMVECs), a protein marker of EndoMT. Therefore, we aimed to investigate the expression level of Î ± -SMA and Notch1-related signaling molecules in PMVECs from BLM-induced rats and determine the relationship between the Notch1 signaling pathway and the expression of Î ± -SMA in PMVECs...
August 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28775096/repetitive-intradermal-bleomycin-injections-evokes-t-helper-cell-2-cytokine-driven-pulmonary-fibrosis
#15
Brijendra Singh, Rajesh K Kasam, Vishwaraj Sontake, Thomas A Wynn, Satish K Madala
IL-4 and IL-13 are major T helper cell (Th) 2 cytokines implicated in the pathogenesis of several lung diseases, including pulmonary fibrosis. In this study, using a novel repetitive intradermal bleomycin model in which mice develop extensive lung fibrosis and a progressive decline in lung function compared to saline-treated control mice, we investigated profibrotic functions of Th2 cytokines. To determine the role of IL-13 signaling in the pathogenesis of bleomycin-induced pulmonary fibrosis, wild-type, IL-13, and IL-4Rα-deficient mice were treated with bleomycin, and lungs were assessed for changes in lung function and pulmonary fibrosis...
August 3, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28763902/-role-of-yes-associated-protein-1-in-angiotensin%C3%A2-induced-pulmonary-fibrosis-in-rats
#16
M X Pan, B B Zheng, N N Sun, Z M Zheng, Q J Yang, Y Meng
Objective: To explore the mechanism of Yes-associated protein 1 (Yap1) in angiotensinⅡ(AngⅡ)-induced pulmonary fibrosis. Methods:In vivo, 18 male Wistar rats were randomly divided into three equal groups with 6 rats in each group, including control group, bleomycin-treated group (BLM), and BLM+ AngⅡ group. 28 days later, the lung tissues in all groups were harvested for the HE and Masson staining as well as the immunohistochemical (IHC) staining for Yap1. In vitro, the isolated fibroblasts were treated with 10(-7) mmol/L AngⅡor the AngⅡ-targeted inhibitor irbesartan for the scheduled time for mRNA and protein expressions of Yap1, PDZ-binding motif (TAZ), and collagen Ⅰusing PCR and Western blot, as well as the translocation test from the nucleus to the cytoplasm of Yap1 and TAZ...
July 25, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28757441/exogenous-nitric-oxide-enhances-the-prophylactic-effect-of-aminoguanidine-a-preferred-inos-inhibitor-on-bleomycin-induced-fibrosis-in-the-lung-implications-for-the-direct-roles-of-the-no-molecule-in-vivo
#17
Chao Chen, Xiao-Jing Yun, Li-Ze Liu, Hong Guo, Lian-Feng Liu, Xiao-Ling Chen
OBJECTIVE: Inducible nitric oxide synthase (iNOS) aggravates and endothelial nitric oxide synthase (eNOS) ameliorates fibrosis in the lung. Our previous study demonstrated that aminoguanidine (AG), a preferred iNOS inhibitor, prevents bleomycin-induced injury and fibrosis in the lung. The diethylenetriamine nitric oxide adduct (DETA/NO) is a slow-release NO donor. Here, to clarify the exact role of the nitric oxide (NO) molecule in the pathogenesis of pulmonary fibrosis in vivo, we observed the effects of inhalation of aerosolized DETA/NO on fibrosis in the lungs of bleomycin-exposed rats with AG treatment, including the effects on the myofibroblast number, collagen deposition, peroxynitrite anion (ONOO(-)) formation, and injury in the lung...
July 27, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28752966/-the-study-of-the-effect-and-mechanism-of-glucagon-like-peptide-1-in-bleomycin-induced-pulmonary-fibrosis-in-mice
#18
Mei Liu, Si Gou, Hai-Tao Chen, Zhong-Hua Chen
OBJECTIVE: To investigate the potential value and mechanisms of glucagon like peptide-1 (GLP-1) on bleomycin (BLM)-induced pulmonary fibrosis in mice. METHODS: Mice were treated with a single sublethal dose of BLM (3 mg/kg ) via intratracheal infusion to produce pulmonary fibrosis, and then liraglutide (2 mg/kg) was given to the mice for 28 days by intraperitoneal injection. 28 days after BLM infusion, the number of total cells, macrophages and neutrophils, lymphocytes, and the content of transforming growth factor-beta 1 (TGF-β1) in bronchoalveolar lavage fluid (BALF) were measured...
July 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28752965/-the-effect-of-sodium-ferulate-in-experimental-pulmonary-fibrosis-via-nalp3-inflammasome
#19
Ju Kuang, Xiao-Lin Wei, Min Xie
OBJECTIVE: To investigate the activation of NALP3 inflammasome in the process of experimental pulmonary fibrosis (PF), and evaluate the effect of sodium ferulate (SF) in the relationship of NALP3 and PF. METHODS: Establishing PF experimental model via bleomycin (BLM) intratracheal injection (BLM group, SF group), treated with SF daily (SF group) or PBS [BLM group, control (CON) group] and mice were executed on day 21. Ashcroft score was used to assess lung fibrosis in mice PF model...
July 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28751023/lysocardiolipin-acyltransferase-regulates-tgf-%C3%AE-mediated-lung-fibroblast-differentiation
#20
Long Shuang Huang, Peiyue Jiang, Carol Feghali-Bostwick, Sekhar P Reddy, Joe G N Garcia, Viswanathan Natarajan
Lysocardiolipin acyltransferase (LYCAT), a cardiolipin remodeling enzyme, plays a key role in mitochondrial function and vascular development. We previously reported that reduced LYCAT mRNA levels in peripheral blood mononuclear cells correlated with poor pulmonary function outcomes and decreased survival in IPF patients. Further LYCAT overexpression reduced lung fibrosis, and LYCAT knockdown accentuated experimental pulmonary fibrosis. NADPH Oxidase 4 (NOX4) expression and oxidative stress are known to contribute to lung fibroblast differentiation and progression of fibrosis...
July 24, 2017: Free Radical Biology & Medicine
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