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Bleomycin pulmonary fibrosis

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https://www.readbyqxmd.com/read/28915889/anti-fibrotic-efficacy-of-nintedanib-in-pulmonary-fibrosis-via-the-inhibition-of-fibrocyte-activity
#1
Seidai Sato, Shintaro Shinohara, Shinya Hayashi, Shun Morizumi, Shuichi Abe, Hiroyasu Okazaki, Yanjuan Chen, Hisatsugu Goto, Yoshinori Aono, Hirohisa Ogawa, Kazuya Koyama, Haruka Nishimura, Hiroshi Kawano, Yuko Toyoda, Hisanori Uehara, Yasuhiko Nishioka
BACKGROUND: Nintedanib, a tyrosine kinase inhibitor that is specific for platelet-derived growth factor receptors (PDGFR), fibroblast growth factor receptors (FGFR), and vascular endothelial growth factor receptors (VEGFR), has recently been approved for idiopathic pulmonary fibrosis. Fibrocytes are bone marrow-derived progenitor cells that produce growth factors and contribute to fibrogenesis in the lungs. However, the effects of nintedanib on the functions of fibrocytes remain unclear...
September 15, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28915065/targeting-hif-1%C3%AE-pdk1-axis-by-dichloroacetate-dca-suppresses-bleomycin-induced-pulmonary-fibrosis
#2
Justin Goodwin, Hyunsung Choi, Meng-Hsiung Hsieh, Michael L Neugent, Jung-Mo Ahn, Heather N Hayenga, Pankaj K Singh, David B Shackelford, In-Kyu Lee, Vladimir Shulaev, Shanta Dhar, Norihiko Takeda, Jung-Whan Kim
RATIONALE: Hypoxia has long been implicated in the pathogenesis of fibrotic diseases. Aberrantly activated myofibroblasts are the primary pathological driver of fibrotic progression, yet how various microenvironmental influences such as hypoxia contribute to their sustained activation and differentiation is poorly understood. OBJECTIVES: As a defining feature of hypoxia is its impact on cellular metabolism, we sought to investigate how hypoxia-induced metabolic reprogramming affects myofibroblast differentiation and fibrotic progression, and to test the pre-clinical efficacy of targeting glycolytic metabolism for the treatment of pulmonary fibrosis...
September 15, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28878780/p2y6-receptor-activation-promotes-inflammation-and-tissue-remodeling-in-pulmonary-fibrosis
#3
Tobias Müller, Susanne Fay, Rodolfo Paula Vieira, Harry Karmouty-Quintana, Sanja Cicko, Cemil Korcan Ayata, Gernot Zissel, Torsten Goldmann, Giuseppe Lungarella, Davide Ferrari, Francesco Di Virgilio, Bernard Robaye, Jean-Marie Boeynaems, Eduardo R Lazarowski, Michael R Blackburn, Marco Idzko
Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis and very few available treatment options. The involvement of the purinergic receptor subtypes P2Y2 and P2X7 in fibrotic lung disease has been demonstrated recently. In this study, we investigated the role of P2Y6 receptors in the pathogenesis of IPF in humans and in the animal model of bleomycin-induced lung injury. P2Y6R expression was upregulated in lung structural cells but not in bronchoalveolar lavage (BAL) cells derived from IPF patients as well as in animals following bleomycin administration...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28878315/cholesterol-modified-hydroxychloroquine-loaded-nanocarriers-in-bleomycin-induced-pulmonary-fibrosis
#4
Li Liu, Jun Ren, Zhiyao He, Ke Men, Ye Mao, Tinghong Ye, Hua Chen, Ling Li, Bocheng Xu, Yuquan Wei, Xiawei Wei
An increasing number of reports have suggested the use of hydroxychloroquine (HCQ) as an adjunct anti-cancer treatment to enhance the chemotherapeutic response, as well as for the treatment of several fibrotic skin diseases and cystic fibrosis. In this study, we synthesized a cholesterol-modified HCQ (Chol-HCQ) and hypothesized that a systemic delivery system with Chol-HCQ nanocarriers could be effective for the treatment of bleomycin-induced pulmonary fibrosis. Chol-HCQ significantly inhibits the proliferation of rat lung fibroblasts, regulates inflammation and ameliorates bleomycin-induced pulmonary fibrosis in rats...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28877257/rosmarinic-acid-potentiates-carnosic-acid-induced-apoptosis-in-lung-fibroblasts
#5
Sana Bahri, Frédérique Mies, Ridha Ben Ali, Mona Mlika, Saloua Jameleddine, Kathleen Mc Entee, Vadim Shlyonsky
Pulmonary fibrosis is characterized by over-population and excessive activation of fibroblasts and myofibroblasts disrupting normal lung structure and functioning. Rosemary extract rich in carnosic acid (CA) and rosmarinic acid (RA) was reported to cure bleomycin-(BLM)-induced pulmonary fibrosis. We demonstrate that CA decreased human lung fibroblast (HLF) viability with IC50 value of 17.13±1.06 μM, while RA had no cytotoxic effect. In the presence of 50 μM of RA, dose-response for CA shifted to IC50 value of 11...
2017: PloS One
https://www.readbyqxmd.com/read/28862882/myeloid-derived-suppressor-cells-are-necessary-for-development-of-pulmonary-hypertension
#6
Andrew J Bryant, Vinayak Shenoy, Chunhua Fu, George Marek, Kyle J Lorentsen, Erica L Herzog, Mark L Brantly, Dorina Avram, Edward W Scott
RATIONALE: Pulmonary hypertension (PH) complicates the care of patients with chronic lung disease, such as idiopathic pulmonary fibrosis (IPF), resulting in a significant increase in morbidity and mortality. Disease pathogenesis is orchestrated by unidentified myeloid-derived cells. OBJECTIVE: We used murine models of PH and pulmonary fibrosis to study the role of circulating myeloid cells in disease pathogenesis and prevention. METHODS: We administered clodronate liposomes to bleomycin treated wild-type mice in order to induce pulmonary fibrosis and PH with a resulting increase in circulating bone marrow-derived cells...
September 1, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28836991/modeling-dna%C3%A2-damage-induced-pneumopathy-in-mice-insight-from-danger-signaling-cascades
#7
REVIEW
Florian Wirsdörfer, Verena Jendrossek
Radiation-induced pneumonitis and fibrosis represent severe and dose-limiting side effects in the radiotherapy of thorax-associated neoplasms leading to decreased quality of life or - as a consequence of treatment with suboptimal radiation doses - to fatal outcomes by local recurrence or metastatic disease. It is assumed that the initial radiation-induced damage to the resident cells triggers a multifaceted damage-signalling cascade in irradiated normal tissues including a multifactorial secretory program. The resulting pro-inflammatory and pro-angiogenic microenvironment triggers a cascade of events that can lead within weeks to a pronounced lung inflammation (pneumonitis) or after months to excessive deposition of extracellular matrix molecules and tissue scarring (pulmonary fibrosis)...
August 24, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28836874/anti-fibrosis-effect-for-hirsutella-sinensis-mycelium-based-on-inhibition-of-mtor-p70s6k-phosphorylation
#8
Huimin Yue, Yarong Zhao, Haining Wang, Feiya Ma, Fei Liu, Sunan Shen, Yayi Hou, Huan Dou
Hirsutella sinensis, cultured in vitro, is an attractive substitute for Cordyceps sinensis as health supplement. The aim of this study was to demonstrate whether H. sinensis mycelium (HSM) attenuates murine pulmonary fibrosis induced by bleomycin and to explore the underlying molecular mechanisms. Using lung fibrosis modle induced by intratracheal instillation of bleomycin (BLM; 4 mg/kg), we observed that the administration of HSM reduced HYP, TGF-β1 and the production of several pro-fibrosis cytokines (α-smooth muscle actin, fibronectin and vimentin) in fibrotic mice lung sections...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/28836192/the-bleomycin-model-of-pulmonary-fibrosis
#9
Tianju Liu, Francina Gonzalez De Los Santos, Sem H Phan
Interstitial lung disease (ILD) comprises a large number of chronic lung disease characterized by varying degrees of inflammation and fibrosis. Mostly they are idiopathic including idiopathic pulmonary fibrosis (IPF), which is a specific disorder characterized by progressive fibrosis leading commonly to end-stage lung disease, respiratory failure, and fatal outcome. IPF and many of these fibrotic ILDs lack effective therapy despite recent approval of two drugs to slow progression in certain IPF patients. Because there are no natural models for IPF, the use of animal models that reproduce key known features of the disease is warranted...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28822966/inhibitory-actions-of-the-nrg-1-erbb4-pathway-in-macrophages-during-tissue-fibrosis-in-heart-skin-and-lung
#10
Zarha Vermeulen, Anne-Sophie Hervent, Lindsey Dugaucquier, Leni Vandekerckhove, Miche Rombouts, Matthias Beyens, Dorien M Schrijvers, Guido R Y De Meyer, Stuart Maudsley, Gilles W De Keulenaer, Vincent Fm Segers
The neuregulin-1 (NRG-1)/ErbB system is an endothelium-controlled paracrine system modulating cardiac performance and adaptation. Recent studies indicate that NRG-1 has anti-fibrotic effects in the left ventricle (LV), which were explained by direct actions on cardiac fibroblasts. However, the NRG-1/ErbB system also regulates the function of macrophages. In this study, we hypothesized that the anti-fibrotic effect of NRG-1 in the heart is at least partially mediated through inhibitory effects on macrophages...
August 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28822963/%C3%AE-1a-subtype-adrenergic-agonist-therapy-for-failing-right-ventricle
#11
Patrick M Cowley, Guan-Ying Wang, Sunil K Joshi, Philip M Swigart, David H Lovett, Paul C Simpson, Anthony J Baker
Failure of the right ventricle (RV) is a serious disease with a poor prognosis and limited treatment options. Signaling by α1-adrenergic receptors (α1-ARs), in particular the α1A-subtype, mediate cardioprotective effects in multiple heart failure models. Recent studies show that chronic treatment with the α1A-subtype agonist A61603 improves function and survival in a model of LV failure. The goal of this study was to determine if chronic A61603 treatment is beneficial in a RV failure model. We used tracheal instillation of the fibrogenic antibiotic bleomycin in mice to induce pulmonary fibrosis, pulmonary hypertension, and RV failure within 2 wk...
August 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28821630/il-17a-deficiency-mitigates-bleomycin-induced-complement-activation-during-lung-fibrosis
#12
Ellyse Cipolla, Amanda J Fisher, Hongmei Gu, Elizabeth A Mickler, Manisha Agarwal, Carol A Wilke, Kevin K Kim, Bethany B Moore, Ragini Vittal
Interleukin 17A (IL-17A) and complement (C') activation have each been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). We have reported that IL-17A induces epithelial injury via TGF-β in murine bronchiolitis obliterans; that TGF-β and the C' cascade present signaling interactions in mediating epithelial injury; and that the blockade of C' receptors mitigates lung fibrosis. In the present study, we investigated the role of IL-17A in regulating C' in lung fibrosis. Microarray analyses of mRNA isolated from primary normal human small airway epithelial cells indicated that IL-17A (100 ng/ml; 24 h; n = 5 donor lungs) induces C' components (C' factor B, C3, and GPCR kinase isoform 5), cytokines (IL8, -6, and -1B), and cytokine ligands (CXCL1, -2, -3, -5, -6, and -16)...
August 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28821451/5-ht7-receptor-antagonism-sb-269970-attenuates-bleomycin-induced-pulmonary-fibrosis-in-rats-via-downregulating-oxidative-burden-and-inflammatory-cascades-and-ameliorating-collagen-deposition-comparison-to-terguride
#13
Mona K Tawfik, Samy Makary
The neurotransmitter 5-hydroxytryptamine (5-HT) is involved in regulation of local tissue inflammation and repair through a set of receptors (5-HT1-7 receptors), which are expressed in the lung. Considering the protective importance of 5-HT receptor antagonists against development of pulmonary fibrosis, we evaluated whether 5-HT7 receptor antagonist (SB-269970) modulates lung inflammatory and fibrogenic processes in comparison with 5-HT2A/B receptor antagonist (terguride), in bleomycin (BLM)-induced idiopathic pulmonary fibrosis (IPF) model...
August 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28821136/discovery-of-enzymatically-depolymerized-heparins-capable-of-treating-bleomycin-induced-pulmonary-injury-and-fibrosis-in-mice
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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