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https://www.readbyqxmd.com/read/28732066/inhibition-of-pulmonary-%C3%AE-carotene-15-15-oxygenase-expression-by-glucocorticoid-involves-ppar%C3%AE
#1
Xiaoming Gong, Raju Marisiddaiah, Lewis P Rubin
β-carotene 15,15'-oxygenase (BCO1) catalyzes the first step in the conversion of dietary provitamin A carotenoids to vitamin A. This enzyme is expressed in a variety of developing and adult tissues, suggesting that its activity may regulate local retinoid synthesis. Vitamin A and related compounds (retinoids) are critical regulators of lung epithelial development, integrity, and injury repair. A balance between the actions of retinoids and glucocorticoids (GCs) promotes normal lung development and, in particular, alveolarization...
2017: PloS One
https://www.readbyqxmd.com/read/28729471/hypoxic-vascular-response-and-ventilation-perfusion-matching-in-end-stage-copd-may-depend-on-p22phox
#2
Chandran Nagaraj, Christoph Tabeling, Bence M Nagy, Pritesh P Jain, Leigh M Marsh, Rita Papp, Michael Pienn, Martin Witzenrath, Bahil Ghanim, Walter Klepetko, E Kenneth Weir, Stefan Heschl, Grazyna Kwapiszewska, Andrea Olschewski, Horst Olschewski
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease in which the amount of emphysema and airway disease may be very different between individuals, even in end-stage disease. Emphysema formation may be linked to the involvement of the small pulmonary vessels. The NAPDH oxidase (Nox) family is emerging as a key disease-related factor in vascular diseases, but currently its role in hypoxia-induced pulmonary remodelling in COPD remains unclear.Here we investigate the role of p22phox, a regulatory subunit of Nox, in COPD lungs, hypoxic pulmonary vasoconstriction (HPV), hypoxia-induced pulmonary vascular remodelling and pulmonary hypertension...
July 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28729000/airway-microbiota-signals-anabolic-and-catabolic-remodeling-in-the-transplanted-lung
#3
Stéphane Mouraux, Eric Bernasconi, Céline Pattaroni, Angela Koutsokera, John-David Aubert, Johanna Claustre, Christophe Pison, Pierre-Joseph Royer, Antoine Magnan, Romain Kessler, Christian Benden, Paola M Soccal, Benjamin J Marsland, Laurent P Nicod
BACKGROUND: Homeostatic turnover of the extracellular matrix conditions the structure and function of the healthy lung. In lung transplantation, long-term management remains limited by Chronic Lung Allograft Dysfunction (CLAD), an umbrella term used for a heterogeneous entity ultimately associated with pathological airway and/or parenchyma remodeling. OBJECTIVE: To assess whether the local cross-talk between the pulmonary microbiota and host cells is a key determinant in the control of lower airway remodeling post-transplantation...
July 17, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28727907/novel-role-of-surfactant-protein-a-in-bacterial-sinusitis
#4
George T Noutsios, Amanda L Willis, Julie G Ledford, Eugene H Chang
BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disorder of the upper airway characterized by chronic inflammation and significant sinonasal remodeling. CRS is comprised of 2 major subgroups, based on whether polyps are present or absent. In some cases, it is characterized by colonization with opportunistic pathogens such as Pseudomonas aeruginosa (PA), Staphylococcus aureus, and other bacteria. The innate immune system of the sinonasal epithelium is the first line of defense against inhaled pathogens...
July 20, 2017: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/28725641/mechanisms-mediating-pediatric-severe-asthma-and-potential-novel-therapies
#5
REVIEW
Aldara Martin Alonso, Sejal Saglani
Although a rare disease, severe therapy-resistant asthma in children is a cause of significant morbidity and results in utilization of approximately 50% of health-care resources for asthma. Improving control for children with severe asthma is, therefore, an urgent unmet clinical need. As a group, children with severe asthma have severe and multiple allergies, steroid resistant airway eosinophilia, and significant structural changes of the airway wall (airway remodeling). Omalizumab is currently the only add-on therapy that is licensed for use in children with severe asthma...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28723660/poly-adp-ribose-polymerase-inhibitors-as-radiosensitizers-a-systematic-review-of-pre-clinical-and-clinical-human-studies
#6
REVIEW
Paul Lesueur, François Chevalier, Jean-Baptiste Austry, Waisse Waissi, Hélène Burckel, Georges Noël, Jean-Louis Habrand, Yannick Saintigny, Florence Joly
BACKGROUND: Poly-(ADP-Ribose)-Polymerase (PARP) inhibitors are becoming important actors of anti-neoplasic agents landscape, with recent but narrow FDA's approvals for ovarian BRCA mutated cancers and prostatic cancer. Nevertheless, PARP inhibitors are also promising drugs for combined treatments particularly with radiotherapy. More than seven PARP inhibitors have been currently developed. Central Role of PARP in DNA repair, makes consider PARP inhibitor as potential radiosensitizers, especially for tumors with DNA repair defects, such as BRCA mutation, because of synthetic lethality...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28720577/lysyl-oxidase-like-protein-loxl2-promotes-lung-metastasis-of-breast-cancer
#7
Fernando Salvador, Alberto Martin, Celia López-Menéndez, Gema Moreno-Bueno, Vanesa Santos, Alberto Vazquez-Naharro, Patricia G Santamaría, Saleta Morales, Pierre Dubus, Laura Muinelo-Romay, Rafael López López, Jason C Tung, Valerie M Weaver, Francisco Portillo, Amparo Cano
The lysyl oxidase-like protein LOXL2 has been suggested to contribute to tumor progression and metastasis, but in vivo evidence has been lacking. Here we provide functional evidence that LOXL2 is a key driver of breast cancer metastasis in two conditional transgenic mouse models of PyMT-induced breast cancer. LOXL2 ablation in mammary tumor cells dramatically decreased lung metastasis, whereas LOXL2 overexpression promoted metastatic tumor growth. LOXL2 depletion or overexpression in tumor cells does not affect extracellular matrix stiffness or organization in primary and metastatic tumors, implying a function for LOXL2 independent of its conventional role in extracellular matrix remodeling...
July 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28720422/drug-targeting-to-myofibroblasts-implications-for-fibrosis-and-cancer
#8
Saleh Yazdani, Ruchi Bansal, Jai Prakash
Myofibroblasts are the key players in extracellular matrix remodeling, a core phenomenon in numerous devastating fibrotic diseases. Not only in organ fibrosis, but also the pivotal role of myofibroblasts in tumor progression, invasion and metastasis has recently been highlighted. Myofibroblast targeting has gained tremendous attention in order to inhibit the progression of incurable fibrotic diseases, or to limit the myofibroblast-induced tumor progression and metastasis. In this review, we outline the origin of myofibroblasts, their general characteristics and functions during fibrosis progression in three major organs: liver, kidneys and lungs as well as in cancer...
July 15, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28718833/coconut-oil-aggravates-pressure-overload-induced-cardiomyopathy-without-inducing-obesity-systemic-insulin-resistance-or-cardiac-steatosis
#9
Ilayaraja Muthuramu, Ruhul Amin, Andrey Postnov, Mudit Mishra, Frank Jacobs, Olivier Gheysens, Paul P Van Veldhoven, Bart De Geest
Studies evaluating the effects of high-saturated fat diets on cardiac function are most often confounded by diet-induced obesity and by systemic insulin resistance. We evaluated whether coconut oil, containing C12:0 and C14:0 as main fatty acids, aggravates pressure overload-induced cardiomyopathy induced by transverse aortic constriction (TAC) in C57BL/6 mice. Mortality rate after TAC was higher (p < 0.05) in 0.2% cholesterol 10% coconut oil diet-fed mice than in standard chow-fed mice (hazard ratio 2.32, 95% confidence interval 1...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28713812/the-biology-of-eosinophils-and-their-role-in-asthma
#10
REVIEW
Claire N McBrien, Andrew Menzies-Gow
This review will describe the structure and function of the eosinophil. The roles of several relevant cell surface molecules and receptors will be discussed. We will also explore the systemic and local processes triggering eosinophil differentiation, maturation, and migration to the lungs in asthma, as well as the cytokine-mediated pathways that result in eosinophil activation and degranulation, i.e., the release of multiple pro-inflammatory substances from eosinophil-specific granules, including cationic proteins, cytokines, chemokines growth factors, and enzymes...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28713373/15-deoxy-delta-12-14-prostaglandin-j2-inhibits-lung-inflammation-and-remodeling-in-distinct-murine-models-of-asthma
#11
Diego S Coutinho, Edna A Anjos-Valotta, Caio V M F do Nascimento, Ana Lucia A Pires, Marcelo H Napimoga, Vinícius F Carvalho, Rafael C Torres, Patrícia M R E Silva, Marco A Martins
15-deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) has been described as an anti-inflammatory lipid mediator in several in vitro and in vivo studies, but its effect on allergic pulmonary inflammation remains elusive. The aim of this study was to investigate the therapeutic potential of 15d-PGJ2 based on distinct murine models of allergic asthma triggered by either ovalbumin (OVA) or house dust mite extract (HDM). Characteristics of lung inflammation, airway hyper-reactivity (AHR), mucus exacerbation, and lung remodeling in sensitized A/J mice treated or not with 15d-PGJ2 were assessed...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28711881/clinical-utility-of-ykl-40-in-polymyositis-dermatomyositis-associated-interstitial-lung-disease
#12
Hironao Hozumi, Tomoyuki Fujisawa, Noriyuki Enomoto, Ran Nakashima, Yasunori Enomoto, Yuzo Suzuki, Masato Kono, Masato Karayama, Kazuki Furuhashi, Akihiro Murakami, Naoki Inui, Yutaro Nakamura, Tsuneyo Mimori, Takafumi Suda
OBJECTIVE: Interstitial lung disease (ILD) is involved in polymyositis/dermatomyositis (PM/DM), a disease associated with poor prognoses. Chitinase-3-like-1 protein (YKL-40) has pleiotropic biological activities involved in inflammation, cell proliferation, and tissue remodeling; however, the clinical application of YKL-40 remains limited. We investigated the clinical significance of YKL-40 in PM/DM-ILD. METHODS: Sixty-nine consecutive patients with PM/DM-ILD and 34 healthy controls were analyzed...
July 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28710117/genetic-and-epigenetic-drivers-of-neuroendocrine-tumors-net
#13
Annunziata Di Domenico, Tabea Wiedmer, Ilaria Marinoni, Aurel Perren
Neuroendocrine tumors (NET) of the gastrointestinal tract and the lung are a rare and heterogeneous group of tumors. The molecular characterization and the clinical classification of these tumors have been evolving slowly and show differences according to organs of origin. Novel technologies such as next-generation sequencing revealed new molecular aspects of NET over the last years. Notably, whole exome/genome sequencing (WES/WGS) approaches underlined the very low mutation rate of well differentiated NET of all organs compared to other malignancies, while the engagement of epigenetic changes in driving NET evolution is emerging...
July 14, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28709839/fungal-immunomodulatory-protein-fve-could-modulate-airway-remodel-through-by-affect-il17-cytokine
#14
Yu-Tzu Lee, Chia-Ta Wu, Hai-Lun Sun, Jiunn-Liang Ko, Ko-Haung Lue
BACKGROUND: Asthma is one of the most common allergic diseases. Our previous studies have reported that FIP-fve in acute allergic mouse model can reduce inflammation, improve the balance of the Th1/Th2 system. However, the effects of reducing airway remodeling on FIP-fve is still unknown. OBJECTIVE: We hypothesized that orally administrated FIP-fve should be able to reduce airway remodeling in chronic allergic models. METHODS: The chronic asthma animal model was established with 6-8 weeks female Balb/c mice...
June 29, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28704475/protective-effect-of-galectin-9-in-murine-model-of-lung-emphysema-involvement-of-neutrophil-migration-and-mmp-9-production
#15
Yuko Horio, Hidenori Ichiyasu, Keisuke Kojima, Naoki Saita, Yohei Migiyama, Toyohisa Iriki, Kazuhiko Fujii, Toshiro Niki, Mitsuomi Hirashima, Hirotsugu Kohrogi
PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and pulmonary emphysema. Persistent inflammation and remodeling of the lungs and airways result in reduced lung function and a lower quality of life. Galectin (Gal)-9 plays a crucial role as an immune modulator in various diseases. However, its role in the pathogenesis of pulmonary emphysema is unknown. This study investigates whether Gal-9 is involved in pulmonary inflammation and changes in emphysema in a porcine pancreatic elastase (PPE)-induced emphysema model...
2017: PloS One
https://www.readbyqxmd.com/read/28700567/recombinant-ccn1-prevents-hyperoxia-induced-lung-injury-in-neonatal-rats
#16
Ruben Vaidya, Ronald Zambrano, Julia K Hummler, Shihua Luo, Matthew R Duncan, Karen Young, Lester F Lau, Shu Wu
BACKGROUND: Cystein rich protein 61 (Cyr61/CCN1) is a member of the CCN family of matricellular proteins that plays an improtant role in tissue development and remodeling. However, the role of CCN1 in in the pathogensis of bronchopulmonary dysplasia (BPD) is unknown. Accordingly, we have investigated the effects of CCN1 on a hyperoxia-induced lung injury model in neonatal rats. METHODS: In experiment 1: newborn rats were randomized to room air (RA) or 85% oxygen (O2) for 7 or 14 days and we assessed the expression of CCN1...
July 12, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28698228/perturbations-to-lysyl-oxidase-expression-broadly-influence-the-transcriptome-of-lung-fibroblasts
#17
Ivana Mižíková, Francesco Palumbo, Tamás Tábi, Susanne Herold, István Vadász, Konstantin Mayer, Werner Seeger, Rory E Morty
Lysyl oxidases are credited with pathogenic roles in lung diseases, including cancer, fibrosis, pulmonary hypertension, congenital diaphragmatic hernia, and bronchopulmonary dysplasia (BPD). Lysyl oxidases facilitate the covalent intra- and inter-molecular cross-linking of collagen and elastin fibers, thereby imparting tensile strength to the extracellular matrix (ECM). Alternative ECM-independent roles have recently been proposed for lysyl oxidases, including regulation of growth factor signaling, chromatin remodeling, and transcriptional regulation; all of which impact cell phenotype...
July 10, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28696800/effect-of-nintedanib-on-airway-inflammation-and-remodeling-in-a-murine-chronic-asthma-model
#18
Hwa Young Lee, Jung Hur, In Kyoung Kim, Ji Young Kang, Hyoung Kyu Yoon, Sook Young Lee, Soon Suk Kwon, Young Kyoon Kim, Chin Kook Rhee
INTRODUCTION: Nintedanib is a multi-tyrosine kinase receptor inhibitor recently approved for treatment of idiopathic pulmonary fibrosis. Although angiogenesis is a key process involved in airway structural changes in patients with bronchial asthma, the effect of nintedanib targeting the angiokinase pathway on airway inflammation and remodeling has not been evaluated. METHODS: We used a 3-month ovalbumin (OVA) challenge mouse model of airway remodeling. Nintedanib was orally administrated during the challenge period, and the effects were examined based on the percentage of airway inflammatory cells, airway hyper-reactivity (AHR), peribronchial goblet cell hyperplasia, total lung collagen and smooth muscle area...
July 11, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28694354/myocardial-upregulation-of-cathepsin-d-by-ischemic-heart-disease-promotes-autophagic-flux-and-protects-against-cardiac-remodeling-and-heart-failure
#19
Penglong Wu, Xun Yuan, Faqian Li, Jianhua Zhang, Wei Zhu, Meng Wei, Jingbo Li, Xuejun Wang
BACKGROUND: Lysosomal dysfunction is implicated in human heart failure for which ischemic heart disease is the leading cause. Altered myocardial expression of CTSD (cathepsin D), a major lysosomal protease, was observed in human heart failure, but its pathophysiological significance has not been determined. METHODS AND RESULTS: Western blot analyses revealed an increase in the precursor but not the mature form of CTSD in myocardial samples from explanted human failing hearts with ischemic heart disease, which is recapitulated in chronic myocardial infarction produced via coronary artery ligation in Ctsd(+/+) but not Ctsd(+/-) mice...
July 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28694203/soluble-epoxide-hydrolase-inhibitor-auda-decreases-bleomycin-induced-pulmonary-toxicity-in-mice-by-inhibiting-the-p38-smad3-pathways
#20
Xin-Wei Dong, Yong-Liang Jia, Ling-Tian Ge, Bo Jiang, Jun-Xia Jiang, Shen Jian, Ya-Chao Jin, Guan Yan, Yun Sun, Qiang-Min Xie
Bleomycin (BLM) has potent tumor cell-killing properties that have given it an important place in cancer chemotherapy, but pulmonary toxicity is its major adverse effect. Soluble epoxide hydrolase (sEH) inhibitors have been reported to have protective effects in fibrosis models, but the effects of AUDA, an sEH inhibitor of BLM-induced pulmonary toxicity and fibrosis, remain to be researched. In this study, we assessed the effects of AUDA on the BLM-induced pulmonary fibrosis in a mouse model, and transforming growth factor (TGF)-β1-induced epithelial proliferation and epithelial-mesenchymal transition (EMT) in vitro by monitoring changes in pulmonary function, inflammatory response, fibrotic remodeling, and signaling pathways...
July 7, 2017: Toxicology
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