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Idiopathic pulmonary fibrosis

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https://www.readbyqxmd.com/read/29050340/nogo-b-promotes-emt-in-lung-fibrosis-via-mmp14-mediates-free-tgf-beta1-formation
#1
Ye Xiong, Jing Zhang, Lingzhi Shi, Yunye Ning, Ying Zhu, Si Chen, Meng Yang, Jingyu Chen, Guo-Wu Zhou, Qiang Li
Idiopathic pulmonary fibrosis (IPF) is a lung disease with an extremely poor prognosis. Epithelial mesenchymal transition (EMT) appearing on the airway epithelial cell plays an essential role in the formation and development of Idiopathic pulmonary fibrosis. In this paper, Bleomycin (BLM)-induced mice model combined with bioinformatics analysis were employed to elucidate the potential mechanism of EMT in pulmonary fibrosis. The obtained results showed that endoplasmic reticulum protein Nogo-b may promote MMP14-mediated proprotein maturation of TGF-β1, accelerating the release of free TGF-β1 in type II airway epithelial cells A549, subsquently, induce the epithelial-mesenchymal transition (EMT) of the cell...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29046395/epithelial-contribution-to-the-pro-fibrotic-stiff-microenvironment-and-myofibroblast-population-in-lung-fibrosis
#2
Marta Gabasa, Paula Duch, Ignasi Jorba, Alícia Giménez, Roberto Lugo, Irina Pavelescu, Fernando Rodríguez-Pascual, Maria Molina-Molina, Antoni Xaubet, Javier Pereda, Jordi Alcaraz
The contribution of epithelial-to-mesenchymal transition (EMT) to the pro-fibrotic stiff microenvironment and myofibroblast accumulation in pulmonary fibrosis remains unclear. We examined EMT-competent lung epithelial cells and lung fibroblasts from control (fibrosis-free) donors or patients with idiopathic pulmonary fibrosis (IPF), which is a very aggressive fibrotic disorder. Cells were cultured on pro-fibrotic conditions including stiff substrata and TGF-β1, and analyzed in terms of morphology, stiffness and expression of EMT/myofibroblast markers and fibrillar collagens...
October 18, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29045951/lifestyle-behaviors-and-clinical-outcomes-in-idiopathic-pulmonary-fibrosis
#3
Baruch Vainshelboim, Jose Oliveira, Shimon Izhakian, Avraham Unterman, Mordechai Reuven Kramer
BACKGROUND: Lifestyle behaviors are not well-characterized in idiopathic pulmonary fibrosis (IPF). OBJECTIVES: To assess the association between lifestyle behaviors and clinical outcomes in patients with IPF. METHODS: A total of 34 IPF patients (median age 68 years) were assessed for daily sitting and weekly walking times using the International Physical Activity Questionnaire by in-person interview at baseline, and they were followed up for up to 40 months...
October 19, 2017: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/29045477/tubastatin-ameliorates-pulmonary-fibrosis-by-targeting-the-tgf%C3%AE-pi3k-akt-pathway
#4
Shigeki Saito, Yan Zhuang, Bin Shan, Svitlana Danchuk, Fayong Luo, Martina Korfei, Andreas Guenther, Joseph A Lasky
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal disease. Histone deacetylase 6 (HDAC6) alters function and fate of various proteins via deacetylation of lysine residues, and is implicated in TGF-β1-induced EMT (epithelial-mesenchymal transition). However, the role of HDAC6 in pulmonary fibrosis is unknown. METHODS: HDAC6 expression in IPF and control lungs was assessed by quantitative real-time PCR (qRT-PCR) and immunoblots. Lung fibroblasts were treated with TGF-β1 ± HDAC6 inhibitors (Tubacin, Tubastatin, ACY1215, or MC1568), and fibrotic markers such as type I collagen were assessed using qRT-PCR and immunoblots...
2017: PloS One
https://www.readbyqxmd.com/read/29044226/bone-marrow-transplant-induced-alterations-in-notch-signaling-promote-pathologic-th17-responses-to-%C3%AE-herpesvirus-infection
#5
S J Gurczynski, X Zhou, M Flaherty, C A Wilke, B B Moore
Idiopathic pneumonia syndrome (IPS) is a common, often fatal, complication following hematopoietic stem cell transplantation (HSCT) characterized by severe pneumonitis and interstitial fibrosis. Fully reconstituted syngeneic bone marrow transplant (BMT) mice infected with murine γ-herpesvirus-68 develop interleukin-17 (IL-17)-driven pneumonitis and fibrosis, which mimics clinical manifestations of IPS. We found CD103+ and CD11b+ dendritic cells (DCs) are selectively deficient for the Notch ligand, DLL4, following BMT and CD4+ T cells isolated from lungs and spleens of infected BMT mice display Notch signaling defects...
October 18, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29043847/smoking-related-interstitial-fibrosis-evidence-of-radiologic-regression-with-advancing-age-and-smoking-cessation
#6
Aurélie Fabre, Ann Treacy, Lisa P Lavelle, Maciek Narski, Nazia Faheem, David Healy, Jonathan D Dodd, Michael P Keane, James J Egan, Gilles Jebrak, Hervé Mal, Marcus W Butler
More data are needed regarding the radiology, co-morbidities and natural history of smoking-related interstitial fibrosis (SRIF), a common pathological finding, mainly described heretofore in association with lung cancer, where respiratory bronchiolitis (RB) usually co-exists. We prospectively acquired high resolution CT scan data (edge-enhancing lung reconstructions) to detect any radiologic interstitial lung abnormality (ILA) in individuals who ultimately underwent surgical lobectomy for lung cancer (n = 20), for radiologic/pathologic correlation...
October 18, 2017: COPD
https://www.readbyqxmd.com/read/29038949/sleep-disorders-and-health-related-quality-of-life-in-patients-with-interstitial-lung-disease
#7
Maria Mavroudi, Despoina Papakosta, Theodore Kontakiotis, Kaliopi Domvri, George Kalamaras, Vasiliki Zarogoulidou, Paul Zarogoulidis, Paschalina Latka, Haidong Huang, Wolfgang Hohenforst-Schmidt, Konstantinos Zarogoulidis
BACKGROUND: Interstitial lung diseases (ILD) are chronic and restrictive lung diseases with poor survival and quality of life. The aim of this study was to investigate the frequency of sleep disorders in idiopathic pulmonary fibrosis (IPF) and sarcoidosis and to assess patients' quality of life in relation to these disorders. METHODS: Forty patients, 19 with IPF, and 21 with sarcoidosis stage II/III were included. They were compared with 15 healthy subjects. All patients performed all-night polysomnography (PSG) and completed the Epworth, Berlin, and Stop-Bang questionnaires...
October 16, 2017: Sleep & Breathing, Schlaf & Atmung
https://www.readbyqxmd.com/read/29035378/molecular-similarities-and-differences-from-human-pulmonary-fibrosis-and-corresponding-mouse-model-maldi-imaging-mass-spectrometry-in-comparative-medicine
#8
Michaela Aichler, Thomas Kunzke, Achim Buck, Na Sun, Maximilian Ackermann, Danny Jonigk, Andreas Gaumann, Axel Walch
Animal models can reproduce some model-specific aspects of human diseases, but some animal models translate poorly or fail to translate to the corresponding human disease. Here, we develop a strategy to systematically compare human and mouse tissues, and conduct a proof-of-concept experiment to identify molecular similarities and differences using patients with idiopathic pulmonary fibrosis and a bleomycin-induced fibrosis mouse model. Our novel approach employs high-throughput tissue microarrays (TMAs) of humans and mice, high-resolution matrix-assisted laser desorption/ionization-Fourier transform-ion cyclotron resonance-mass spectrometry imaging (MALDI-FT-ICR-MSI) to spatially resolve mass spectra at the level of specific metabolites, and hierarchical clustering and pathway enrichment analysis to identify functionally similar/different molecular patterns and pathways in pathological lesions of humans and mice...
October 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29035148/treatment-of-pulmonary-fibrosis-with-sirna-against-a-collagen-specific-chaperone-hsp47-in-vitamin-a-coupled-liposomes
#9
Mitsuo Otsuka, Masanori Shiratori, Hirofumi Chiba, Koji Kuronuma, Yasushi Sato, Yoshiro Niitsu, Hiroki Takahashi
BACKGROUND: Pulmonary fibrosis is a life-threatening pathological state of progressive interstitial lung diseases, such as idiopathic pulmonary fibrosis. Myofibroblasts are known to play a critical role in the pathogenesis of pulmonary fibrosis. This study aimed to evaluate the inhibitory effect of a small interfering RNA (siRNA) on a collagen-specific chaperone heat shock protein 47 (HSP47). The siRNA was preferentially delivered to myofibroblasts in a bleomycin (BLM)-induced pulmonary fibrosis rat model using siRNA against HSP47, encapsulated in a vitamin A-coupled liposome (VA-lip-siRNA HSP47)...
October 16, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/29024319/prognostic-significance-of-glasgow-prognostic-score-in-patients-with-acute-exacerbation-of-idiopathic-pulmonary-fibrosis
#10
Hye S Kang, Kang W Cho, Soon S Kwon, Yong H Kim
BACKGROUND AND OBJECTIVE: The Glasgow prognostic score (GPS) reflects the host systemic inflammatory response and is a validated independent prognostic factor in lung cancer. We investigated GPS as a potential predictive factor of clinical outcomes in idiopathic pulmonary fibrosis (IPF) patients with acute exacerbation (AE). METHODS: This was a retrospective study performed between January 2006 and March 2016 in Bucheon St. Mary's Hospital, The Catholic University of Korea...
October 12, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/29021387/timing-of-onset-of-symptoms-in-people-with-idiopathic-pulmonary-fibrosis
#11
Thomas Hewson, Tricia M McKeever, Jack E Gibson, Vidya Navaratnam, Richard B Hubbard, John P Hutchinson
Little is known about when symptoms of idiopathic pulmonary fibrosis first develop. We identified incident cases of idiopathic pulmonary fibrosis-clinical syndrome (IPF-CS) from a UK primary care database and assessed the frequency of consultations for common symptoms in the 5 years prior to diagnosis. 1671 cases were identified with 5 years of data prior to diagnosis. Breathlessness was the most common symptom, followed by cough. Cases were significantly more likely than controls to experience these symptoms (p<0...
October 11, 2017: Thorax
https://www.readbyqxmd.com/read/29019707/glutaminolysis-promotes-collagen-translation-and-stability-via-%C3%AE-ketoglutarate-mediated-mtor-activation-and-proline-hydroxylation
#12
Jing Ge, Huachun Cui, Na Xie, Sami Banerjee, Sijia Guo, Shubham Dubey, Stephen Barnes, Gang Liu
Glutaminolysis is the metabolic process of glutamine, of which aberration has been implicated in several pathogeneses. While we and others recently found a diversity of metabolic dysregulations in organ fibrosis, it is unknown if glutaminolysis regulates the pro-fibrotic activities of myofibroblasts, the primary effector in this pathology. In this study, we found that lung myofibroblasts demonstrated significantly augmented glutaminolysis that was mediated by elevated Glutaminase 1 (Gls1). Inhibition of glutaminolysis by specific Gls1 inhibitors CB-839 and BPTES as well as Gls1 siRNA blunted the expression of collagens, but not that of Fibronectin, Elastin or myofibroblastic marker smooth muscle actin α (SMA-α)...
October 11, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29019702/inhibition-of-phgdh-attenuates-bleomycin-induced-pulmonary-fibrosis
#13
Robert B Hamanaka, Recep Nigdelioglu, Angelo Y Meliton, Yufeng Tian, Leah J Witt, Erin O'Leary, Kaitlyn A Sun, Parker S Woods, David Wu, Brandon Ansbro, Shawn Ard, Jason M Rohde, Nickolai O Dulin, Robert D Guzy, Gökhan M Mutlu
Organ fibrosis, including idiopathic pulmonary fibrosis (IPF), is associated with significant morbidity and mortality. Since currently available therapies have limited effect, there is need to better understand the mechanisms by which organ fibrosis occurs. We have recently reported that TGF-β, a key cytokine which promotes fibrogenesis, induces the expression of the enzymes of the de novo serine and glycine synthesis pathway in human lung fibroblasts and that phosphoglycerate dehydrogenase (PHGDH, the first and rate limiting enzyme of the pathway) is required to promote collagen protein synthesis downstream of TGF-β...
October 11, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29017422/nintedanib-for-idiopathic-pulmonary-fibrosis
#14
Abisola Tepede, Dinesh Yogaratnam
OBJECTIVE: To review the pharmacology, safety, and efficacy of nintedanib for the treatment of idiopathic pulmonary fibrosis (IPF). METHODS: A literature search was conducted via PubMed using the MeSH term "idiopathic pulmonary fibrosis" combined with the key word "nintedanib." Additional online searches using Google Scholar, Micromedex, and PubMed were performed to obtain prescribing and cost information. RESULTS: One phase II and 2 replicate phase III clinical trials that examined the safety and efficacy of nintedanib for IPF were identified...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/28993806/genetics-in-idiopathic-pulmonary-fibrosis-pathogenesis-prognosis-and-treatment
#15
REVIEW
Amarpreet Kaur, Susan K Mathai, David A Schwartz
Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia (IIP), is characterized by irreversible scarring of the lung parenchyma and progressive decline in lung function leading to eventual respiratory failure. The prognosis of IPF is poor with a median survival of 3-5 years after diagnosis and no curative medical therapies. Although the pathogenesis of IPF is not well understood, there is a growing body of evidence that genetic factors contribute to disease risk. Recent studies have identified common and rare genetic variants associated with both sporadic and familial forms of pulmonary fibrosis, with at least one-third of the risk for developing fibrotic IIP explained by common genetic variants...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28993537/long-term-treatment-of-patients-with-idiopathic-pulmonary-fibrosis-with-nintedanib-results-from-the-tomorrow-trial-and-its-open-label-extension
#16
Luca Richeldi, Michael Kreuter, Moisés Selman, Bruno Crestani, Anne-Marie Kirsten, Wim A Wuyts, Zuojun Xu, Katell Bernois, Susanne Stowasser, Manuel Quaresma, Ulrich Costabel
The TOMORROW trial of nintedanib comprised a randomised, placebo-controlled, 52-week period followed by a further blinded treatment period and an open-label extension. We assessed outcomes across these periods in patients randomised to nintedanib 150 mg twice daily or placebo at the start of TOMORROW. The annual rate of decline in FVC was -125.4 mL/year (95% CI -168.1 to -82.7) in the nintedanib group and -189.7 mL/year (95% CI -229.8 to -149.6) in the comparator group. The adverse event profile of nintedanib remained consistent throughout the studies...
October 9, 2017: Thorax
https://www.readbyqxmd.com/read/28991645/lung-diseases-of-the-elderly-cellular-mechanisms
#17
REVIEW
Kori Ascher, Sharon J Elliot, Gustavo A Rubio, Marilyn K Glassberg
Natural lung aging is characterized by molecular and cellular changes in multiple lung cell populations. These changes include shorter telomeres, increased expression of cellular senescence markers, increased DNA damage, oxidative stress, apoptosis, and stem cell exhaustion. Aging, combined with the loss of protective repair processes, correlates with the development and incidence of chronic respiratory diseases, including idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease. Ultimately, it is the interplay of age-related changes in biology and the subsequent responses to environmental exposures that largely define the physiology and clinical course of the aging lung...
November 2017: Clinics in Geriatric Medicine
https://www.readbyqxmd.com/read/28990892/hepatitis-c-and-pulmonary-fibrosis
#18
Oğuzhan Okutan, Ömer Ayten
Hepatitis C is one of the most important infectious agents worldwide. There are conflicting results regarding the relationship between pulmonary fibrosis and hepatitis C. It is thought that hepatitis C may play a role in the development or exacerbations of idiopathic pulmonary fibrosis, but no clear link between hepatitis C and pulmonary fibrosis development has been demonstrated yet to date. In the recent era, indirect effects of hepatitis C rather than a direct effect are more suspected on pulmonary fibrosis...
June 2017: Tüberküloz Ve Toraks
https://www.readbyqxmd.com/read/28987380/the-disturbed-redox-balance-in-pulmonary-fibrosis-is-modulated-by-the-plant-flavonoid-quercetin
#19
C Veith, M Drent, A Bast, F J van Schooten, A W Boots
Idiopathic pulmonary fibrosis (IPF) is characterized by a disturbed pulmonary redox balance associated with inflammation. To restore this balance, antioxidants are often suggested as therapy for IPF but previous clinical trials with these compounds and their precursors have not been successful in the clinic. The exogenous antioxidant quercetin, which has a versatile antioxidant profile and is effective in restoring a disturbed redox balance, might be a better candidate. The aim of this study was to evaluate the protective effect of quercetin on oxidative and inflammatory markers in IPF...
October 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28987319/mitochondria-telomeres-and-cell-senescence-implications-for-lung-ageing-and-disease
#20
REVIEW
Jodie Birch, Peter J Barnes, Joao F Passos
Cellular senescence, the irreversible loss of replicative capacity in somatic cells, plays a causal role in the development of age-related pathology and in a number of age-related chronic inflammatory diseases. The ageing lung is marked by an increasing number of senescent cells, and evidence is mounting that senescence may directly contribute to a number of age-related respiratory diseases, including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Telomere dysfunction and alterations in mitochondrial homeostasis frequently occur in cellular senescence and are important to the development of the often detrimental senescence-associated secretory phenotype (SASP)...
October 4, 2017: Pharmacology & Therapeutics
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