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Bleomycin pulmonary fibrosis

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https://www.readbyqxmd.com/read/28651005/optimization-of-a-murine-and-human-tissue-model-to-recapitulate-dermal-and-pulmonary-features-of-systemic-sclerosis
#1
Tomoya Watanabe, Tetsuya Nishimoto, Logan Mlakar, Jonathan Heywood, Maya Malaab, Stanley Hoffman, Carol Feghali-Bostwick
The murine bleomycin (BLM)-induced fibrosis model is the most widely used in systemic sclerosis (SSc) studies. It has been reported that systemic delivery of BLM via continuous diffusion from subcutaneously implanted osmotic minipumps can cause fibrosis of the skin, lungs, and other internal organs. However, the mouse strain, dosage of BLM, administration period, and additional important features differ from one report to the next. In this study, by employing the pump model in C57BL/6J mice, we show a dose-dependent increase in lung fibrosis by day 28 and a transient increase in dermal thickness...
2017: PloS One
https://www.readbyqxmd.com/read/28642129/fucoxanthin-inhibits-profibrotic-protein-expression-in-vitro-and-attenuates-bleomycin-induced-lung-fibrosis-in-vivo
#2
Sun Young Ma, Won Sun Park, Dae-Sung Lee, Grace Choi, Mi-Jin Yim, Jeong Min Lee, Won-Kyo Jung, Sae Gwang Park, Su-Kil Seo, Sung Jae Park, Il Yong Han, Yung Hyun Choi, Il-Whan Choi
Pulmonary fibrosis, a potentially fatal disease, results from acute and chronic interstitial lung diseases. Fucoxanthin (Fx), a carotenoid found in brown seaweed, shows a wide range of pharmacological activities. In this study, we investigated the antifibrotic effects of fucoxanthin and their underlying molecular mechanisms in transforming growth factor-beta1 (TGF-β1)-stimulated human pulmonary fibroblasts (HPFs). Thus, the effects of Fx on TGF-β1-induced expression of fibrotic factors, such as alpha-smooth muscle actin (α-SMA), type 1 collagen, fibronectin, and interleukin-6 (IL-6), in HPFs were investigated...
June 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28629359/forced-expiration-measurements-in-mouse-models-of-obstructive-and-restrictive-lung-diseases
#3
Fien C Devos, André Maaske, Annette Robichaud, Lore Pollaris, Sven Seys, Carolina Aznar Lopez, Erik Verbeken, Matthias Tenbusch, Rik Lories, Benoit Nemery, Peter Hm Hoet, Jeroen Aj Vanoirbeek
BACKGROUND: Pulmonary function measurements are important when studying respiratory disease models. Both resistance and compliance have been used to assess lung function in mice. Yet, it is not always clear how these parameters relate to forced expiration (FE)-related parameters, most commonly used in humans. We aimed to characterize FE measurements in four well-established mouse models of lung diseases. METHOD: Detailed respiratory mechanics and FE measurements were assessed concurrently in Balb/c mice, using the forced oscillation and negative pressure-driven forced expiration techniques, respectively...
June 19, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28621667/xist-mir-139-axis-regulates-bleomycin-blm-induced-extracellular-matrix-ecm-and-pulmonary-fibrosis-through-%C3%AE-catenin
#4
Yichun Wang, Ying Liang, Junming Luo, Jing Nie, Huiming Yin, Qiong Chen, Jing Dong, Jixiang Zhu, Jiamei Xia, Wei Shuai
Pulmonary fibrosis (PF), characterized by the destruction of lung tissue architecture and the abnormal deposition of extracellular matrix (ECM) proteins, currently has no satisfactory treatment. In the present study, we investigated the hypothesis that XIST play a promotive role in bleomycin (BLM)-induced ECM and pulmonary fibrosis; XIST exerts its effect through miR-139 regulation. XIST expression was upregulated in lung tissues derived from BLM-induced mouse model of PF, and was positively correlated with β-catenin and ECM protein levels, respectively...
May 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28619646/time-dependent-effects-of-hjp272-an-endothelin-receptor-antagonist-in-bleomycin-induced-pulmonary-fibrosis
#5
Xingjian Liu, Nikhil Khadtare, Hardek Patel, Ralph Stephani, Jerome Cantor
Using a lipopolysaccharide (LPS) model of acute lung injury, we have previously shown that endothelin-1 (ET-1), a potent mediator of vasoconstriction, may act as a "gatekeeper" for the influx of inflammatory cells into the lung. To further investigate the potential of ET-1 to limit the progression of lung injury, hamsters were treated with an endothelin receptor antagonist (ERA), HJP272, either 1 h prior to intratracheal instillation of bleomycin (BLM) or 24 h afterwards. Lung injury and repair were examined by measuring the following parameters: 1) histopathological changes; 2) neutrophil content in bronchoalveolar lavage fluid (BALF); 3) lung collagen content; 4) tumor necrosis factor receptor 1 (TNFR1) expression by BALF macrophages; 5) BALF levels of: a) transforming growth factor beta-1 (TGF-β1), b) stromal cell-derived factor 1 (commonly referred to as CXCL12), and c) platelet-derived growth factor BB (PDGF-BB); 6) alveolar septal cell apoptosis (as measured by the TUNEL assay)...
June 12, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28615638/pharmacodynamic-and-pharmacokinetic-assessment-of-pulmonary-rehabilitation-mixture-for-the-treatment-of-pulmonary-fibrosis
#6
Juanjuan Zhao, Yan Ren, Yubei Qu, Wanglin Jiang, Changjun Lv
Pulmonary rehabilitation mixture (PRM), a Chinese herbal medicine formula, has been used to treat pulmonary fibrosis for decades. In this study, we systematically evaluated the pharmacodynamic and pharmacokinetic performance of PRM. The pharmacodynamic results showed that PRM could improve the condition of CoCl2-stimulated human type II alveolar epithelial cells, human pulmonary microvascular endothelial cells, human lung fibroblasts and pulmonary fibrosis rats induced by bleomycin, PRM treatment reduced the expression of platelet-derived growth factor, fibroblast growth factor, toll-like receptor 4, high-mobility group box protein 1 and hypoxia-inducible factor 1α...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28613983/azithromycin-attenuates-myofibroblast-differentiation-and-lung-fibrosis-development-through-proteasomal-degradation-of-nox4
#7
Kazuya Tsubouchi, Jun Araya, Shunsuke Minagawa, Hiromichi Hara, Akihiro Ichikawa, Nayuta Saito, Tsukasa Kadota, Nahoko Sato, Masahiro Yoshida, Yusuke Kurita, Kenji Kobayashi, Saburo Ito, Yu Fujita, Hirofumi Utsumi, Haruhiko Yanagisawa, Mitsuo Hashimoto, Hiroshi Wakui, Yutaka Yoshii, Takeo Ishikawa, Takanori Numata, Yumi Kaneko, Hisatoshi Asano, Makoto Yamashita, Makoto Odaka, Toshiaki Morikawa, Katsutoshi Nakayama, Yoichi Nakanishi, Kazuyoshi Kuwano
Accumulation of profibrotic myofibroblasts is involved in the process of fibrosis development during idiopathic pulmonary fibrosis (IPF) pathogenesis. TGFB (transforming growth factor beta) is one of the major profibrotic cytokines for myofibroblast differentiation and NOX4 (NADPH oxidase 4) has an essential role in TGFB-mediated cell signaling. Azithromycin (AZM), a second-generation antibacterial macrolide, has a pleiotropic effect on cellular processes including proteostasis. Hence, we hypothesized that AZM may regulate NOX4 levels by modulating proteostasis machineries, resulting in inhibition of TGFB-associated lung fibrosis development...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28611390/protective-and-therapeutic-effect-of-felodipine-against-bleomycin-induced-pulmonary-fibrosis-in-mice
#8
Ken-Ichiro Tanaka, Tomomi Niino, Tomoaki Ishihara, Ayaka Takafuji, Takahiro Takayama, Yuki Kanda, Toshifumi Sugizaki, Fumiya Tamura, Shota Kurotsu, Masahiro Kawahara, Tohru Mizushima
Idiopathic pulmonary fibrosis (IPF) involves alveolar epithelial injury and abnormal collagen production caused by activated fibroblasts; transforming growth factor (TGF)-β1 is implicated in this activation. In this study, we screened for chemicals capable of inhibiting TGF-β1-induced collagen production in cultured fibroblasts from medicines already in clinical use. We selected felodipine based on its extent of collagen production inhibition, clinical safety profile, and other pharmacological activity. Felodipine is a dihydropyridine Ca(2+) channel blocker that has been used clinically to treat patients with high blood pressure...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28611243/optimization-of-a-collagen-targeted-positron-emission-tomography-probe-for-molecular-imaging-of-pulmonary-fibrosis
#9
Pauline Désogère, Luis F Tapias, Tyson A Rietz, Nicholas Rotile, Francesco Blasi, Helen Day, Justin Elliot, Bryan C Fuchs, Michael Lanuti, Peter Caravan
There is a large unmet need for a simple, accurate, non-invasive, quantitative and high resolution imaging modality to detect lung fibrosis at early stage and to monitor disease progression. Overexpression of collagen is a hallmark of organ fibrosis. Here, we describe the optimization of a collagen-targeted positron emission tomography (PET) probe for staging pulmonary fibrosis. Methods: Six peptides were synthesized, conjugated to a copper chelator, and radiolabeled with copper-64. The collagen affinity of each probe was measured in a plate-based assay...
June 13, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28608724/dexamethasone-reduces-serum-level-of-il-17-in-bleomycin-a5-induced-rats-model-of-pulmonary-fibrosis
#10
Aihua Wang, Fengqiang Wang, Yingqiu Yin, Min Zhang, Ping Chen
BACKGROUND: Pulmonary fibrosis is a chronic progressive disease with limited therapeutic options and inflammatory cytokines play important roles in the pathogenesis of pulmonary fibrosis. MATERIAL AND METHOD: Here, we investigated the changes of TGF-β1, IL-8, and IL-17 in the serum of bleomycin-A5-induced rats model of pulmonary fibrosis. 120 healthy male Wistar rats were randomly divided into three groups, the control group (n = 30), the model group (n = 45) and the dexamethasone (DEX) group (n = 45)...
June 13, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28606286/-effect-of-water-soluble-c-60-fullerenes-on-pulmonary-fibrosis-induced-by-bleomycin-in-mice
#11
R Dong, M Liu, X X Huang, Z Liu, D Y Jiang, H J Xiao, H P Dai
Objective: To evaluate the role of water-soluble C(60) fullerenes in mice model of lung injury and fibrosis that induced by bleomycin. Methods: A total of 20 healthy C57BL/6J mice were randomly divided into normal control group, bleomycin group, high dose C(60) group, low dose C(60) group, each group with 5 mice. Mice were induced pulmonary fibrosis by intratracheal injection of bleomycin except the normal control group, which was induced by saline instead. In low dose C(60) group and high dose C(60) group, 1 mg·kg(-1)·d(-1) and 10 mg·kg(-1)·d(-1) water-soluble C(60) fullerenes was injected into mice intraperitoneally every day, which began from one day before intratracheal instillation of bleomycin until the end of observation...
June 13, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28598023/nintedanib-reduces-ventilation-augmented-bleomycin-induced-epithelial-mesenchymal-transition-and-lung-fibrosis-through-suppression-of-the-src-pathway
#12
Li-Fu Li, Kuo-Chin Kao, Yung-Yang Liu, Chang-Wei Lin, Ning-Hung Chen, Chung-Shu Lee, Chih-Wei Wang, Cheng-Ta Yang
Mechanical ventilation (MV) used in patients with acute respiratory distress syndrome (ARDS) can increase lung inflammation and pulmonary fibrogenesis. Src is crucial in mediating the transforming growth factor (TGF)-β1-induced epithelial-mesenchymal transition (EMT) during the fibroproliferative phase of ARDS. Nintedanib, a multitargeted tyrosine kinase inhibitor that directly blocks Src, has been approved for the treatment of idiopathic pulmonary fibrosis. The mechanisms regulating interactions among MV, EMT and Src remain unclear...
June 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28591554/nlrp3-participates-in-the-regulation-of-emt-in-bleomycin-induced-pulmonary-fibrosis
#13
Rui Tian, Yong Zhu, Jiayi Yao, Xiaoxiao Meng, Jinfeng Wang, Hui Xie, Ruilan Wang
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and irreversible lung disease. Studies have shown that epithelial-mesenchymal transition (EMT) plays an important role in the development of IPF. The NLRP3 inflammasome is reported to be activated and play an important role in many respiratory diseases. However, whether the NLRP3 inflammasome is activated in alveolar epithelial cells as well as the regulatory role of NLRP3 in EMT have not been reported. In this study, we transfected NLRP3 siRNA into A549 and RLE-6TN cells and treated them with bleomycin (BLM) for 24h...
June 4, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28577568/pirfenidone-inhibits-myofibroblast-differentiation-and-lung-fibrosis-development-during-insufficient-mitophagy
#14
Yusuke Kurita, Jun Araya, Shunsuke Minagawa, Hiromichi Hara, Akihiro Ichikawa, Nayuta Saito, Tsukasa Kadota, Kazuya Tsubouchi, Nahoko Sato, Masahiro Yoshida, Kenji Kobayashi, Saburo Ito, Yu Fujita, Hirofumi Utsumi, Haruhiko Yanagisawa, Mitsuo Hashimoto, Hiroshi Wakui, Yutaka Yoshii, Takeo Ishikawa, Takanori Numata, Yumi Kaneko, Hisatoshi Asano, Makoto Yamashita, Makoto Odaka, Toshiaki Morikawa, Katsutoshi Nakayama, Kazuyoshi Kuwano
BACKGROUND: Pirfenidone (PFD) is an anti-fibrotic agent used to treat idiopathic pulmonary fibrosis (IPF), but its precise mechanism of action remains elusive. Accumulation of profibrotic myofibroblasts is a crucial process for fibrotic remodeling in IPF. Recent findings show participation of autophagy/mitophagy, part of the lysosomal degradation machinery, in IPF pathogenesis. Mitophagy has been implicated in myofibroblast differentiation through regulating mitochondrial reactive oxygen species (ROS)-mediated platelet-derived growth factor receptor (PDGFR) activation...
June 2, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28573228/moxibustion-has-a-positive-effect-on-pulmonary-fibrosis-an-alternative-approach
#15
Lin Cheng, Rong Li, Mijuan Zhou, Fuhong Li, Quanying Chang, Cuixia Li, Xuejing Lu
BACKGROUND: An increasing number of people suffered idiopathic fibrosis (IPF) and the current treatment was far from clinical satisfaction. Moxibustion, another effective and safe unconventional therapy, had been introduced to treat this refractory disease. The study aimed to investigate the effect of moxibustion on a bleomycin A5-induced pulmonary fibrosis model. MATERIALS AND METHODS: Sprague-dawley (SD) rats were randomly allocated to the blank group, model group, moxibustion group, and prednisone group, for which they received no treatment, modeling, moxibustion treatment and prednisone treatment...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28571757/hmgb1-promotes-hlf-1-proliferation-and-ecm-production-through-activating-hif1-%C3%AE-regulated-aerobic-glycolysis
#16
JianNing Xu, JingYing Li, ZhiHong Yu, HaiWei Rao, Shu Wang, HaiBing Lan
Aerobic glycolysis is a crucial event in fibroblast differentiation, and extracellular matrix (ECM) production in the progression of pulmonary fibrosis (PF). Abnormal high mobility group protein B1 (HMGB1) activation is involved in the pathogenesis of PF. However, whether aerobic glycolysis contributes to HMGB1-induced fibroblast proliferation and ECM production in PF has not yet been determined. In this study, we investigated the effects of HMGB1 on human embryonic lung fibroblast (HLF-1) proliferation, ECM production, and aerobic glycolysis...
May 29, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28557137/modulation-of-cd11c-lung-dendritic-cells-in-respect-to-tgf-%C3%AE-in-experimental-pulmonary-fibrosis
#17
Kaustav Chakraborty, Soumya Chatterjee, Arindam Bhattacharyya
Idiopathic Pulmonary fibrosis (IPF) is a deadly progressive lung disease with very few treatment options till now. Bleomycin-induced pulmonary fibrosis (BIPF) is a commonly used mice model in IPF research. TGF-β1 has been shown to play a key role in pulmonary fibrosis (PF). Dendritic cell (DC) acts as a bridge between innate and adaptive immune system. The coexistence of chronic inflammation sustained by mature DCs with fibrosis suggests that inflammatory phenomenon has key importance in the pathogenesis of pulmonary fibrosis...
May 30, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28543309/adenovirus-vector-expressing-keratinocyte-growth-factor-using-cag-promoter-impaired-pulmonary-function-of-elastase-induced-emphysema
#18
Hiroshi Oki, Takuya Yazawa, Yasuko Baba, Yumi Kanegae, Hanako Sato, Seiko Sakamoto, Takahisa Goto, Izumu Saito, Kiyoyasu Kurahashi
Pulmonary emphysema impairs quality of life and increases mortality. Previous studies demonstrated that administration of KGF before elastase instillation prevented pulmonary emphysema in mice. We hypothesized that KGF could improve pulmonary function, and that the therapeutic administration of KGF would restore damaged lungs caused by elastase instillation in an animal model. We constructed KGF expressing adenovirus vector, which prevented bleomycin induced pulmonary fibrosis in the previous study. Adenovirus vector (1...
May 24, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28534139/pulmonary-emphysema-cross-linking-with-pulmonary-fibrosis-and-vice-versa-a-non-usual-experimental-intervention-with-elastase-and-bleomycin
#19
Isabella Cattani-Cavalieri, Adriane Graça Reis, Emanuel Kennedy-Feitosa, Vanessa Pinho-Ribeiro, Manuella Lanzetti, Lycia Brito Gitirana, Bruna Romana-Souza, Luis Cristóvão Porto, Samuel Santos Valença
Elastase (PPE) is usually used for emphysema models, whereas bleomycin (BLM) is used for fibrosis models. The aim of this study was to investigate the effect of BLM in PPE-induced emphysema, as well as the effect of PPE in BLM-induced fibrosis. C57BL/6 mice were divided into five groups: control, PPE, BLM, PPE + BLM, and BLM + PPE. Mice received saline, PPE (3 U/mouse), or BLM (20 U/kg) by intranasal instillation. Mice from the BLM and BLM + PPE groups received BLM on day 0 and saline or PPE on day 21, respectively...
May 23, 2017: Inflammation
https://www.readbyqxmd.com/read/28533545/treatment-effects-of-the-traditional-chinese-medicine-shenks-in-bleomycin-induced-lung-fibrosis-through-regulation-of-tgf-beta-smad3-signaling-and-oxidative-stress
#20
Haiyan Chu, Ying Shi, Shuai Jiang, Qicheng Zhong, Yongqiang Zhao, Qingmei Liu, Yanyun Ma, Xiangguang Shi, Weifeng Ding, Xiaodong Zhou, Jimin Cui, Li Jin, Gang Guo, Jiucun Wang
Pulmonary fibrosis is a kind of devastating interstitial lung disease due to the limited therapeutic strategies. Traditional Chinese medicine (TCM) practices have put forth Shenks as a promising treatment approach. Here, we performed in vivo study and in vitro study to delineate the anti-fibrotic mechanisms behind Shenks treatment for pulmonary fibrosis. We found that regardless of the prophylactic or therapeutic treatment, Shenks was able to attenuate BLM-induced-fibrosis in mice, down regulate extracellular matrix genes expression, and reduce collagen production...
May 22, 2017: Scientific Reports
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