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https://www.readbyqxmd.com/read/28424787/integrating-transcriptomics-proteomics-and-metabolomics-profiling-with-system-pharmacology-for-the-delineation-of-long-term-therapeutic-mechanisms-of-bufei-jianpi-formula-in-treating-copd
#1
Peng Zhao, Jiansheng Li, Ya Li, Yange Tian, Liping Yang, Suyun Li
In previous work, we identified 145 active compounds from Bufei Jianpi formula (BJF) by system pharmacology and found that BJF showed short-term effect on chronic obstructive pulmonary disease (COPD) rats. Here, we applied the transcriptomic, proteomic, and metabolomics approaches to illustrate the long-term anti-COPD action and its system mechanism of BJF. BJF has obvious anti-COPD effect through decreasing inflammatory cytokines level, preventing protease-antiprotease imbalance and collagen deposition on week 32 by continuous oral administration to rats from weeks 9 to 20...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28424691/increased-autophagy-related-5-gene-expression-is-associated-with-collagen-expression-in-the-airways-of-refractory-asthmatics
#2
Audrey H Poon, David F Choy, Fazila Chouiali, Rakhee K Ramakrishnan, Bassam Mahboub, Severine Audusseau, Andrea Mogas, Jeffrey M Harris, Joseph R Arron, Catherine Laprise, Qutayba Hamid
BACKGROUND: Fibrosis, particularly excessive collagen deposition, presents a challenge for treating asthmatic individuals. At present, no drugs can remove or reduce excessive collagen in asthmatic airways. Hence, the identification of pathways involved in collagen deposition would help to generate therapeutic targets to interfere with the airway remodeling process. Autophagy, a cellular degradation process, has been shown to be dysregulated in various fibrotic diseases, and genetic association studies in independent human populations have identified autophagy-related 5 (ATG5) to be associated with asthma pathogenesis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28424241/microbiota-induced-antibodies-are-essential-for-host-inflammatory-responsiveness-to-sterile-and-infectious-stimuli
#3
Daniel Cisalpino, Caio T Fagundes, Camila B Brito, Fernando R Ascenção, Celso M Queiroz-Junior, Angélica T Vieira, Lirlândia P Sousa, Flávio A Amaral, Leda Q Vieira, Jacques R Nicoli, Mauro M Teixeira, Danielle G Souza
The indigenous intestinal microbiota is frequently considered an additional major organ of the human body and exerts profound immunomodulating activities. Germ-free (GF) mice display a significantly different inflammatory responsiveness pattern compared with conventional (CV) mice, and this was dubbed a "hyporesponsive phenotype." Taking into account that the deposition of immune complexes is a major event in acute inflammation and that GF mice have a distinct Ig repertoire and B cell activity, we aimed to evaluate whether this altered Ig repertoire interferes with the inflammatory responsiveness of GF mice...
April 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28421197/ginsenoside-rg1-ameliorates-cigarette-smoke-induced-airway-fibrosis-by-suppressing-the-tgf-%C3%AE-1-smad-pathway-in-vivo-and-in-vitro
#4
Sibin Guan, Qian Liu, Fengfeng Han, Wen Gu, Lin Song, Yue Zhang, Xuejun Guo, Weiguo Xu
Small airway fibrosis is a key pathological process accompanying chronic obstructive pulmonary disease (COPD) and includes fibroblast/myofibroblast transdifferentiation and excessive extracellular matrix deposition. Ginsenoside Rg1, one of the main active ingredients of Panax ginseng, has been shown to exert an antifibrotic effect in many tissues. However, little is known about the underlying mechanism and whether ginsenoside Rg1 can exert an effect on small airway fibrosis. We investigated the anti-small airway fibrosis effects of ginsenoside Rg1 in human embryonic lung fibroblasts and in COPD rats...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28417017/galectin-1-inhibition-attenuates-profibrotic-signaling-in-hypoxia-induced-pulmonary-fibrosis
#5
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/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/28413391/minocycline-induced-hyperpigmentation-in-a-patient-treated-with-erlotinib-for-non-small-cell-lung-adenocarcinoma
#7
Ann T Bell, John W Roman, Max L Gratrix, Christina E Brzezniak
INTRODUCTION: While epidermal growth factor receptor (EGFR) inhibitors have improved progression-free survival in patients with non-small cell lung cancer (NSCLC), one of the most common adverse effects is papulopustular skin eruption, which is frequently severe enough to be treated with oral minocycline or doxycycline. CASE: We present a case of an 87-year-old man who developed a severe papulopustular skin eruption secondary to erlotinib therapy for NSCLC. Control of the eruption with 100 mg of minocycline twice daily for 8 months eventually led to blue-gray skin hyperpigmentation...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28411230/interaction-of-12-15-lipoxygenase-with-fatty-acids-alters-the-leukocyte-kinetics-leading-to-improved-post-myocardial-infarction-healing
#8
Ganesh V Halade, Vasundhara Kain, Kevin A Ingle, Sumanth D Prabhu
The metabolic transformation of fatty acids to form oxylipids using 12/15lipoxygenase (LOX) can promote either resolving or non-resolving inflammation. However, the mechanism of how 12/15LOX interacts with PUFA (polyunsaturated fatty acids) in post-myocardial infarction (MI) healing is unclear. Here, we reported the role of 12/15LOX in post-MI cardiac remodeling in a PUFA (10% w/w, 22 Kcal) enriched environment. Wild-type (WT; C57BL/6J) and 12/15LOX null (12/15LOX(-/-)) male mice of 8-12-weeks age were fed PUFA-enriched diet for 1 month and subjected to permanent coronary artery ligation...
April 14, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28410559/the-irony-of-iron-overload-and-iron-deficiency-in-chronic-obstructive-pulmonary-disease
#9
Suzanne M Cloonan, Sharon Mumby, Ian M Adcock, Augustine M K Choi, Kian Fan Chung, Gregory J Quinlan
Chronic obstructive pulmonary disease (COPD) is a debilitating inflammatory lung disease associated with cigarette smoking and is third leading cause of death worldwide. With the recent emergence of genome wide association studies (GWAS), the identification of multiple COPD susceptibility genes has enhanced and expanded our understanding of the pathogenic mechanisms associated with this debilitating lung disease. An example of such a pathogenic mechanism is the role of iron metabolism in the onset and progression of COPD...
April 14, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28410043/optimising-inhaler-technique-in-chronic-obstructive-pulmonary-disease-a-complex-issue
#10
Jo Riley, Phillip Krüger
Inhaled therapies play a central role in the management of chronic obstructive pulmonary disease (COPD); however, studies indicate that many patients do not use their inhaled medication as directed, resulting in decreased medication delivery and suboptimal disease control. Key factors that should be considered when evaluating whether patients are achieving optimal outcomes with inhaled therapies are: if patients are using a correct inhalation technique; if patients have adequate dexterity to use the prescribed inhaler; if patients have sufficient inspiratory flow rate to achieve adequate lung deposition (for dry powder inhalers); and if the inhaler is accepted by the patient...
April 13, 2017: British Journal of Nursing: BJN
https://www.readbyqxmd.com/read/28408888/prevention-of-bleomycin-induced-pulmonary-inflammation-and-fibrosis-in-mice-by-paeonol
#11
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/28407046/rage-mediated-extracellular-matrix-proteins-accumulation-exacerbates-hysu-induced-pulmonary-hypertension
#12
Daile Jia, Yuhu He, Qian Zhu, Huan Liu, Caojian Zuo, Guilin Chen, Ying Yu, Ankang Lu
Aims: Extracellular matrix (ECM) proteins accumulation contributes to the progression of pulmonary arterial hypertension (PAH), a rare and fatal cardiovascular condition defined by high pulmonary arterial pressure, whether primary, idiopathic, or secondary to other causes. The receptor for advanced glycation end products (RAGE) is constitutively expressed in the lungs and plays an important role in ECM deposition. Nonetheless, the mechanisms by which RAGE mediates ECM deposition/formation in pulmonary arteries and its roles in PAH progression remain unclear...
April 11, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28402575/impaired-proliferation-and-differentiation-of-the-conducting-airway-epithelium-associated-with-bronchiolitis-obliterans-after-sulfur-mustard-inhalation-injury-in-rats
#13
Matthew D McGraw, Jaqueline S Rioux, Rhonda B Garlick, Raymond C Rancourt, Carl W White, Livia A Veress
RationaleSulfur mustard (SM) is a chemical warfare agent that causes chronic airway remodeling. The current study's objective was to assess for changes to the bronchiolar epithelium after SM exposure to explain its contribution to chronic airway remodeling.Materials and MethodsAdult male rats were exposed to a sub-lethal dose of SM inhalation (1.0 - 1.2 mg/kg) for 50 minutes. Histological sections of the bronchiolar epithelium were analyzed for changes using H&E, trichrome, and immunofluorescent staining for acetylated tubulin (AT) and club cell secretory protein (CCSP)...
April 11, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28400405/nutritional-approaches-for-managing-obesity-associated-metabolic-diseases
#14
Rachel Botchlett, Shih-Lung Woo, Mengyang Liu, Ya Pei, Xin Guo, Honggui Li, Chaodong Wu
Obesity is an ongoing pandemic and serves as a causal factor of a wide spectrum of metabolic diseases including diabetes, fatty liver disease, and cardiovascular disease. Much evidence has demonstrated that nutrient overload initiates or exacerbates inflammatory responses in tissues/organs involved in the regulation of systemic metabolic homeostasis. This obesity-associated inflammation is usually at a low-grade and viewed as metabolic inflammation. When it exists continuously, inflammation inappropriately alters metabolic pathways and impairs insulin signaling cascades in peripheral tissues/organs such as adipose tissue, the liver and skeletal muscle, resulting in local fat deposition and insulin resistance and systemic metabolic dysregulation...
April 11, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28397820/bitter-taste-receptor-agonists-mitigate-features-of-allergic-asthma-in-mice
#15
Pawan Sharma, Roslyn Yi, Ajay P Nayak, Nadan Wang, Francesca Tang, Morgan J Knight, Shi Pan, Brian Oliver, Deepak A Deshpande
Asthma is characterized by airway inflammation, mucus secretion, remodeling and hyperresponsiveness (AHR). Recent research has established the bronchodilatory effect of bitter taste receptor (TAS2R) agonists in various models. Comprehensive pre-clinical studies aimed at establishing effectiveness of TAS2R agonists in disease models are lacking. Here we aimed to determine the effect of TAS2R agonists on features of asthma. Further, we elucidated a mechanism by which TAS2R agonists mitigate features of asthma...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28395719/-alphacalcidol-combined-with-dexamethasone-for-reducing-pulmonary-fibrosis-in-mice-and-its-mechanism
#16
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/28395346/carbon-nanotubes-in-the-human-respiratory-tract-clearance-modeling
#17
Robert Sturm
Clearance of single-wall carbon nanotubes (SWCNT, diameter: 5 nm) and multi-wall carbon nanotubes (MWCNT, diameter: 50 nm) in the respiratory tract was predicted for various age groups (infants, children, adolescents, and adults). The model was founded on the assumption that lung clearance takes place in three distinct phases: (i) fast mucociliary clearance, (ii) slow bronchial clearance, and (iii) alveolar clearance. To each of these phases a specific fraction of deposited particles was attributed, the amount of which depended on particles' geometry and particles' deposition sites in the respiratory system...
March 1, 2017: Annals of Work Exposures and Health
https://www.readbyqxmd.com/read/28391751/isolated-aa-amyloidosis-of-the-radial-nerve
#18
Teresa Pérez-de la Fuente, Javier Fernández-Jara, Pilar Rodríguez-Urcelay, Jose Jiménez-Heffernan, Ángel Juárez
BACKGROUND: Amyloidosis affecting peripheral nerve is usually seen in primary amyloidosis. METHODS: We are reporting on the case of a 74-year-old man with a 16-month history of progressive left radial nerve paralysis. Perioperative imaging detected an enlarged radial nerve in the middle-distal part of the arm. The patient had an antecedent of amyloid deposits in the lung. RESULTS: A radial nerve amyloidosis was suspected and confirmed with a biopsy assisted by ultrasonography, resulting in a secondary amyloidosis form...
April 1, 2017: Hand: Official Journal of the American Association for Hand Surgery
https://www.readbyqxmd.com/read/28391040/pegylated-composite-nanoparticles-of-plga-and-polyethylenimine-for-safe-and-efficient-delivery-of-pdna-to-lungs
#19
Atul Kolte, Sushilkumar Patil, Pierre Lesimple, John W Hanrahan, Ambikanandan Misra
Achieving stable, efficient and non-toxic pulmonary gene delivery is most challenging requirement for successful gene therapy to lung. Composite nanoparticles (NPs) of the poly(lactic-co-glycolic acid) (PLGA) and cationic polymer polyethyleneimine (PEI) is an efficient alternative to viral and liposomal vectors for the pulmonary delivery of pDNA. NPs with different weight ratios (0-12.5%w/w) of PLGA/PEI were prepared and characterized for size, morphology, surface charge, pDNA loading and in vitro release. The in vitro cell uptake and transfection studies in the CFBE41o-cell line revealed that NPs with 10% w/w PEI were more efficient but they exhibited significant cytotoxicity in MTT assays, challenging the safety of this formulation...
April 6, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28390837/the-influence-of-mannitol-on-morphology-and-disintegration-of-spray-dried-nano-embedded-microparticles
#20
Afra Torge, Philipp Grützmacher, Frank Mücklich, Marc Schneider
Nano-embedded microparticles represent a promising approach to deliver nanoparticles to the lungs. Microparticles with an appropriate aerodynamic diameter enable an application by dry powder inhaler and the transport of nanoparticles into the airways. By disintegration after deposition, nanoparticles can be released to exhibit their advantages such as a sustained drug release and delivery of the drug across the mucus barrier. The use of an appropriate matrix excipient to embed the nanoparticles is essential for the necessary disintegration and release of nanoparticles...
April 5, 2017: European Journal of Pharmaceutical Sciences
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