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Bleomycin pulmonary fibrosis

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https://www.readbyqxmd.com/read/28434932/combinatorial-treatment-of-idiopathic-pulmonary-fibrosis-using-nanoparticles-with-prostaglandin-e-and-sirna-s
#1
O B Garbuzenko, V Ivanova, V Kholodovych, D C Reimer, K R Reuhl, E Yurkow, D Adler, T Minko
Inhalation delivery of prostaglandin E (PGE2) in combination with selected siRNA(s) was proposed for the efficient treatment of idiopathic pulmonary fibrosis (IPF). Nanostructured lipid carriers (NLC) were used as a delivery system for PGE2 with and without siRNAs targeted to MMP3, CCL12, and HIF1Alpha mRNAs. The model of IPF was developed in SKH1 mice by intratracheal administration of bleomycin at a dose of 1.5U/kg. Results showed that NLC-PGE2 in combination with three siRNAs delivered locally to the lungs by inhalation markedly reduced mouse body mass, substantially limited hydroxyproline content in the lungs and disturbances of the mRNAs and protein expression, restricted lung tissue damage and prevented animal mortality...
April 18, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28422760/cannabinoid-cb1-receptor-overactivity-contributes-to-the-pathogenesis-of-idiopathic-pulmonary-fibrosis
#2
Resat Cinar, Bernadette R Gochuico, Malliga R Iyer, Tony Jourdan, Tadafumi Yokoyama, Joshua K Park, Nathan J Coffey, Hadass Pri-Chen, Gergő Szanda, Ziyi Liu, Ken Mackie, William A Gahl, George Kunos
Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease without effective treatment, highlighting the need for identifying new targets and treatment modalities. The pathogenesis of IPF is complex, and engaging multiple targets simultaneously might improve therapeutic efficacy. To assess the role of the endocannabinoid/cannabinoid receptor 1 (endocannabinoid/CB1R) system in IPF and its interaction with inducible nitric oxide synthase (iNOS) as dual therapeutic targets, we analyzed lung fibrosis and the status of the endocannabinoid/CB1R system and iNOS in mice with bleomycin-induced pulmonary fibrosis (PF) and in lung tissue and bronchoalveolar lavage fluid (BALF) from patients with IPF, as well as controls...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28420366/pirfenidone-attenuates-bleomycin-induced-pulmonary-fibrosis-in-mice-by-regulating-nrf2-bach1-equilibrium
#3
Yuan Liu, Fuai Lu, Lirong Kang, Zhihua Wang, Yongfu Wang
BACKGROUND: Oxidative stress is one of the important factors involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The equilibrium of Nuclear factor-erythroid-related factor 2 (Nrf2)/[BTB (broad-complex, tramtrack and bric-a-brac) and CNC (cap'n'collar protein) homology 1, Bach1] determines the expression level of antioxidant factors, further regulating the function of oxidation/antioxidation capacity. Pirfenidone (PFD) is one of two currently for IPF therapy approved drugs...
April 18, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28417017/galectin-1-inhibition-attenuates-profibrotic-signaling-in-hypoxia-induced-pulmonary-fibrosis
#4
Jaymin J Kathiriya, Niyati Nakra, Jenna Nixon, Puja S Patel, Vijay Vaghasiya, Ahmed Alhassani, Zhi Tian, Diane Allen-Gipson, Vrushank Davé
Idiopathic pulmonary fibrosis (IPF) is characterized by lung remodeling arising from epithelial injury, aberrant fibroblast growth, and excessive deposition of extracellular matrix. Repeated epithelial injury elicits abnormal wound repair and lung remodeling, often associated with alveolar collapse and edema, leading to focal hypoxia. Here, we demonstrate that hypoxia is a physiological insult that contributes to pulmonary fibrosis (PF) and define its molecular roles in profibrotic activation of lung epithelial cells...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28415591/the-purinergic-receptor-subtype-p2y2-mediates-chemotaxis-of-neutrophils-and-fibroblasts-in-fibrotic-lung-disease
#5
Tobias Müller, Susanne Fay, Rodolfo Paula Vieira, Harry Karmouty-Quintana, Sanja Cicko, Korcan Ayata, Gernot Zissel, Torsten Goldmann, Giuseppe Lungarella, Davide Ferrari, Francesco Di Virgilio, Bernard Robaye, Jean-Marie Boeynaems, Michael R Blackburn, Marco Idzko
Idiopathic pulmonary fibrosis (IPF) is a devastating disease with few available treatment options. Recently, the involvement of purinergic receptor subtypes in the pathogenesis of different lung diseases has been demonstrated. Here we investigated the role of the purinergic receptor subtype P2Y2 in the context of fibrotic lung diseases.The concentration of different nucleotides was measured in the broncho-alveolar lavage (BAL) fluid derived from IPF patients and animals with bleomycin-induced pulmonary fibrosis...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414242/discovery-of-2-2-ethyl-6-4-2-3-hydroxyazetidin-1-yl-2-oxo-ethyl-piperazin-1-yl-8-methyl-imidazo-1-2-a-pyridin-3-yl-methyl-amino-4-4-fluorophenyl-thiazole-5-carbonitrile-glpg1690-a-first-in-class-autotaxin-inhibitor-undergoing-clinical-evaluation-for-the-treatment
#6
Nicolas Desroy, Christopher Housseman, Xavier Bock, Agnès Joncour, Natacha Bienvenu, Laëtitia Cherel, Virginie Labeguere, Emilie Rondet, Christophe Peixoto, Jean-Marie Joël Grassot, Olivier Picolet, Denis Annoot, Nicolas Triballeau, Alain Monjardet, Emanuelle Wakselman, Veronique Roncoroni, Sandrine Le Tallec, Roland Blanque, Celine Cottereaux, Nele Vandervoort, Thierry Christophe, Patrick Mollat, Marieke B A C Lamers, Marielle Auberval, Boska Hrvacic, Jovica Ralic, Line Oste, Ellen Van der Aar, Reginald Brys, Bertrand Heckmann
Autotaxin is a circulating enzyme with a major role in the production of lysophosphatic acid (LPA) species in blood. A role for the autotaxin/LPA axis has been suggested in many disease areas including pulmonary fibrosis. Structural modifications of the known autotaxin inhibitor lead compound 1, to attenuate hERG inhibition, remove CYP3A4 time-dependent inhibition and improve pharmacokinetic properties, led to the identification of clinical candidate GLPG1690 (11). Compound 11 was able to cause a sustained reduction of LPA levels in plasma in vivo and was shown to be efficacious in a bleomycin-induced pulmonary fibrosis model in mice, and in reducing extra-cellular matrix deposition in the lung whilst also reducing LPA 18:2 content in bronchoalveolar lavage fluid...
April 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28412654/nigella-sativa-a-traditional-tunisian-herbal-medicine-attenuates-bleomycin-induced-pulmonary-fibrosis-in-a-rat-model
#7
Anouar Abidi, Alexandre Robbe, Nadia Kourda, Saloua Ben Khamsa, Alexandre Legrand
The present study investigated the effects of Nigella sativa oil (NSO) on bleomycin (BLM)-induced lung fibrosis in rats. The rat model of pulmonary fibrosis (PF) was established by intratracheal instillation of BLM, and the effect of 1ml/kg oral NSO treatment once daily observed. The effect of NSO was studied over a period of 50daysusing (1)H RMN analysis on the urine and broncho alveolar lavage fluid (Balf) of the rats. Histopathological (inflammation and fibrosis) and immunohistochemical (TGF-β1 density) changes were evaluated...
April 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28408888/prevention-of-bleomycin-induced-pulmonary-inflammation-and-fibrosis-in-mice-by-paeonol
#8
Meng-Han Liu, An-Hsuan Lin, Hsin-Kuo Ko, Diahn-Warng Perng, Tzong-Shyuan Lee, Yu Ru Kou
Pulmonary fibrosis is a severe and progressive disease that is characterized by an abnormal deposition of extracellular matrix, such as collagens. The pathogenesis of this disease may be initiated by oxidative damage of lung epithelial cells by fibrogenic stimuli, leading to lung inflammation, which in turn promotes various lung fibrotic responses. The profibrogenic effect of transforming growth factor-β1 (TGF-β1) on lung fibroblasts is crucial for the pathogenesis of this disease. Paeonol, the main phenolic compound present in the Chinese herb Paeonia suffruticosa, has antioxidant and anti-inflammatory properties...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28408209/role-of-mir-34a-in-tgf-%C3%AE-1-and-drug-induced-epithelial-mesenchymal-transition-in-alveolar-type-ii-epithelial-cells
#9
Mikihisa Takano, Chinami Nekomoto, Masashi Kawami, Ryoko Yumoto
Epithelial-mesenchymal transition (EMT) of alveolar type II epithelial cells may play an important role in the pulmonary fibrosis induced by drugs such as bleomycin (BLM) and methotrexate (MTX). In this study, we examined the role of microRNAs (miRNAs) in drug-induced EMT using RLE/Abca3, a cell line having alveolar type II cell-like phenotype. Based on the screening using miRNA microarray analysis, it was found that the expression of some miRNAs, such as miR-34a, was increased by transforming growth factor (TGF)-β1 and BLM...
April 10, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28400960/longitudinal-assessment-of-bleomycin-induced-lung-fibrosis-by-micro-ct-correlates-with-histological-evaluation-in-mice
#10
Francesca Ruscitti, Francesca Ravanetti, Jeroen Essers, Yanto Ridwan, Sasha Belenkov, Wim Vos, Francisca Ferreira, Alex KleinJan, Paula van Heijningen, Cedric Van Holsbeke, Antonio Cacchioli, Gino Villetti, Franco Fabio Stellari
BACKGROUND: The intratracheal instillation of bleomycin in mice induces early damage to alveolar epithelial cells and development of inflammation followed by fibrotic tissue changes and represents the most widely used model of pulmonary fibrosis to investigate human IPF. Histopathology is the gold standard for assessing lung fibrosis in rodents, however it precludes repeated and longitudinal measurements of disease progression and does not provide information on spatial and temporal distribution of tissue damage...
2017: Multidisciplinary Respiratory Medicine
https://www.readbyqxmd.com/read/28395719/-alphacalcidol-combined-with-dexamethasone-for-reducing-pulmonary-fibrosis-in-mice-and-its-mechanism
#11
Xiaoyu Yang, Ling Wu, Guoping Li, Qin Ran, Lei Zhang
Objective To study the effect of alphacalcidol and dexamethasone on pulmonary fibrosis and its mechanism. Methods Forty C57BL/6 mice were randomly divided into five groups: normal control group, pulmonary fibrosis group, alphacalcidol group, dexamethasone group, dexamethasone combined with alphacalcidol group. The normal control group was given 0.5 μL/g normal saline by one-time intratracheal injection as well as 0.2 mL normal saline by daily intragastric infusion. The other groups received 0.5 μL/g bleomycin solution by one-time intratracheal injection; besides, the pulmonary fibrosis group were subjected to 0...
April 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28389259/autophagy-induction-by-celastrol-augments-protection-against-bleomycin-induced-experimental-pulmonary-fibrosis-in-rats-role-of-adaptor-protein-p62-sqstm1
#12
Thomas Divya, Anandasadagopan Sureshkumar, Ganapasam Sudhandiran
Pulmonary fibrosis (PF) is a chronic pulmonary disease of unknown cause with high mortality. Autophagy is an important homeostatic process that decides the fate of cells under stress conditions. This study is aimed to investigate whether impaired autophagic activity leads to fibrosis and pharmacological induction of autophagy provides protection against bleomycin (BLM)-induced PF. A single dose of BLM (3 U/kg body weight) was administered intratracheally to induce fibrosis in rats. Celastrol, a triterpenoid (5 mg/kg/body weight, intraperitoneally) was given in every 81 h for a period of 28 days...
April 4, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28386328/kallistatin-protects-against-bleomycin-induced-idiopathic-pulmonary-fibrosis-by-inhibiting-angiogenesis-and-inflammation
#13
Xiaoping Huang, Xiao Wang, Xiaolan Xie, Shulan Zeng, Zhaofa Li, Xianxiang Xu, Huiyong Yang, Fei Qiu, Junsheng Lin, Yong Diao
Aberrant angiogenesis and vascular remodeling are the main features of idiopathic pulmonary fibrosis. Kallistatin is an anti-angiogenic peptide with known effects on endothelial cells. This study aimed to demonstrate that kallistatin has beneficial effects on bleomycin (BLM)-induced pulmonary fibrosis in a rat model by inhibiting angiogenesis. Twenty-five rats were randomly divided into five experimental groups: (A) Saline only (SA)-as the negative control, (B) BLM only (BLM)-as the model group, (C) BLM and 0...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28385812/sirtuin-7-is-decreased-in-pulmonary-fibrosis-and-regulates-the-fibrotic-phenotype-of-lung-fibroblasts
#14
Anne Elizabeth Wyman, Zahid Noor, Rita Fishelevich, Virginia Lockatell, Nirav G Shah, Nevins W Todd, Sergei P Atamas
Pulmonary fibrosis is a severe condition with no cure and limited therapeutic options. Better understanding of its pathophysiology is needed. Recent studies have suggested that pulmonary fibrosis may be driven by accelerated aging-related mechanisms. Sirtuins (SIRTs), particularly SIRT1, -3, and -6, are well-known mediators of aging, however limited data exist on the contribution of sirtuins to lung fibrosis. We assessed the mRNA and protein levels of all seven known sirtuins in primary lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD) in comparison with lung fibroblasts from healthy controls...
April 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28381537/type-i-collagen-targeted-pet-probe-for-pulmonary-fibrosis-detection-and-staging-in-preclinical-models
#15
Pauline Désogère, Luis F Tapias, Lida P Hariri, Nicholas J Rotile, Tyson A Rietz, Clemens K Probst, Francesco Blasi, Helen Day, Mari Mino-Kenudson, Paul Weinreb, Shelia M Violette, Bryan C Fuchs, Andrew M Tager, Michael Lanuti, Peter Caravan
Pulmonary fibrosis is scarring of the lungs that can arise from radiation injury, drug toxicity, environmental or genetic causes, and for unknown reasons [idiopathic pulmonary fibrosis (IPF)]. Overexpression of collagen is a hallmark of organ fibrosis. We describe a peptide-based positron emission tomography (PET) probe ((68)Ga-CBP8) that targets collagen type I. We evaluated (68)Ga-CBP8 in vivo in the bleomycin-induced mouse model of pulmonary fibrosis. (68)Ga-CBP8 showed high specificity for pulmonary fibrosis and high target/background ratios in diseased animals...
April 5, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28365359/leflunomide-prevents-ros-induced-systemic-fibrosis-in-mice
#16
Florence Morin, Niloufar Kavian, Sandrine Chouzenoux, Olivier Cerles, Carole Nicco, Christiane Chéreau, Frédéric Batteux
Systemic sclerosis (SSc) is a connective tissue disorder characterized by fibrosis of the skin and inner organs, vasculopathy and immunological abnormalities. Recent insights into the polarization of macrophages in scleroderma and into the implication of STAT6 and KLF4 in this process have prompted us to investigate the effects of the inhibition of STAT6 signaling pathway by leflunomide in mice. SSc was induced in BALB/c mice by daily subcutaneous injections of hypochlorous acid (HOCl) or bleomycin. Mice were treated (or not) every other day, for 4 or 6 weeks, by leflunomide...
March 30, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28365154/activation-and-overexpression-of-sirt1-attenuates-lung-fibrosis-via-p300
#17
Zhilin Zeng, Sheng Cheng, Huilong Chen, Qinghai Li, Yinan Hu, Qi Wang, Xianying Zhu, Jun Wang
Persistent fibroblast activation is a predominant feature of idiopathic pulmonary fibrosis (IPF), but the transcriptional and epigenetic mechanisms controlling this process are not well understood. Silent information regulator type-1 (Sirt1) is a member of class Ⅲ histone deacetylase with important regulatory roles in a variety of pathophysiologic processes, but its role in fibrotic lung diseases is not clearly elucidated. Sirt1 expression in lung tissues of IPF patients and in a mouse model of bleomycin (BLM)-induced lung fibrosis were evaluated by immunofluorescence...
March 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28364627/protective-role-of-rhapontin-in-experimental-pulmonary-fibrosis-in-vitro-and-in-vivo
#18
Lijun Tao, Juan Cao, Wencheng Wei, Haifeng Xie, Mian Zhang, Chaofeng Zhang
BACKGROUND: Pulmonary fibrosis is a scaring process related to chronic lung injury of all causes. The treatment options for pulmonary fibrosis are very limited. Rhapontin has anti-inflammatory effect and anti-proliferative activity which is widely distributed in the medicinal plants of Rheum genus in China. However, the anti-fibrotic activities of rhapontin have not been previously investigated. METHODS: The effect of rhapontin on TGF-β1-mediated extracellular matrix (ECM) deposition in primary lung fibroblast (PLF) cells, on TGF-β1 secretion in LPS-stimulated human THP-1 derived macrophages in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis was investigated in vivo...
March 29, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28357073/effect-of-bosentan-is-correlated-with-mmp-9-timp-1-ratio-in-bleomycin-induced-pulmonary-fibrosis
#19
Wan-Li Zuo, Jie-Min Zhao, Ji-Xiong Huang, Wei Zhou, Ze-Hong Lei, Yan-Ming Huang, Yan-Fen Huang, Hai-Gang Li
Pulmonary fibrosis (PF) is a life-threatening non-tumorous disease characterized by progressive fibrosis and worsening lung function. Various drugs, such as bleomycin, can contribute to lung injury and PF, with lung injury potentially occurring in 10% of bleomycin users. Bleomycin is the most commonly used drug in the establishment of an animal model of PF in rats. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) serve an important role in controlling tissue organization and fibrosis following injury...
February 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28353632/attenuation-of-bleomycin-induced-pulmonary-fibrosis-in-rats-with-s-allyl-cysteine
#20
Takuma Tsukioka, Shigekazu Takemura, Yukiko Minamiyama, Shinjiro Mizuguchi, Michihito Toda, Shigeru Okada
Pulmonary fibrosis is a complex disease with high mortality and morbidity. As there are currently no effective treatments, development of new strategies is essential for improving therapeutic outcomes. S-allyl cysteine (SAC) is a constituent of aged garlic extract that has demonstrated efficacy as an antioxidant and anti-inflammatory agent. The current study examines the effects of SAC on pulmonary fibrosis induced by a single intratracheal instillation of bleomycin (2.5 mg/kg). SAC was administered to rats as 0...
March 29, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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