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Apoptosis : An International Journal on... Dec 2023Pulmonary fibrosis (PF) is a disease in which excessive extracellular matrix (ECM) accumulation occurs in pulmonary mesenchyme, which induces the destruction of alveolar... (Review)
Review
Pulmonary fibrosis (PF) is a disease in which excessive extracellular matrix (ECM) accumulation occurs in pulmonary mesenchyme, which induces the destruction of alveolar structures and poor prognosis. Macrophage death is responsible for ECM accumulation after alveolar epithelial injury in PF. Depending on the local micro-environments, macrophages can be polarized to either classically activated (M1) or alternatively activated (M2) macrophage phenotypes. In general, M1 macrophages can promote inflammation and sterilization, stop the continuous damage process and prevent excessive repair, while M2 macrophages are anti-inflammatory and promote tissue repair, and excessive M2 macrophage activity may inhibit the absorption and degradation of ECM. Emerging evidence has revealed that death forms such as pyroptosis mediated by inflammasome affect polarization direction and ultimately lead to the development of PF. Pharmacological manipulation of macrophages death signals may serve as a logical therapeutic strategy for PF. This review will focus on the current state of knowledge regarding the regulation and underlying mechanisms of macrophages and their mediators in the influence of macrophage death on the development of PF. We expect to provide help in developing effective therapeutic strategies in clinical settings.
Topics: Humans; Macrophages, Alveolar; Pulmonary Fibrosis; Apoptosis; Macrophages; Inflammation
PubMed: 37707713
DOI: 10.1007/s10495-023-01888-4 -
JCI Insight Jul 2023Multiorgan fibrosis in systemic sclerosis (SSc) accounts for substantial mortality and lacks effective therapies. Lying at the crossroad of TGF-β and TLR signaling,...
Multiorgan fibrosis in systemic sclerosis (SSc) accounts for substantial mortality and lacks effective therapies. Lying at the crossroad of TGF-β and TLR signaling, TGF-β-activated kinase 1 (TAK1) might have a pathogenic role in SSc. We therefore sought to evaluate the TAK1 signaling axis in patients with SSc and to investigate pharmacological TAK1 blockade using a potentially novel drug-like selective TAK1 inhibitor, HS-276. Inhibiting TAK1 abrogated TGF-β1 stimulation of collagen synthesis and myofibroblasts differentiation in healthy skin fibroblasts, and it ameliorated constitutive activation of SSc skin fibroblasts. Moreover, treatment with HS-276 prevented dermal and pulmonary fibrosis and reduced the expression of profibrotic mediators in bleomycin-treated mice. Importantly, initiating HS-276 treatment even after fibrosis was already established prevented its progression in affected organs. Together, these findings implicate TAK1 in the pathogenesis of SSc and identify targeted TAK1 inhibition using a small molecule as a potential strategy for the treatment of SSc and other fibrotic diseases.
Topics: Mice; Animals; Fibrosis; Scleroderma, Systemic; Pulmonary Fibrosis; Fibroblasts
PubMed: 37306632
DOI: 10.1172/jci.insight.165358 -
Expert Review of Respiratory Medicine Jun 2020: Idiopathic pulmonary fibrosis (IPF) is a chronic, devastating, and progressive lung disease that is characterized by fibrosis and respiratory failure. IPF holds high... (Review)
Review
: Idiopathic pulmonary fibrosis (IPF) is a chronic, devastating, and progressive lung disease that is characterized by fibrosis and respiratory failure. IPF holds high morbidity and poor prognosis and still faces considerable problems of reliable diagnosis and valid prognosis. A growing body of literature have reported changes in the level of various biomarkers in IPF patients, which means that they are expected to become a new tool for the clinical practice of IPF.: We reviewed the recent literature about biomarkers and focus on the role they play in IPF. We systematically searched Medline/PubMed through February 2020. Many works of literature have shown that a variety of biomolecules and genomics played multiple roles in the diagnosis or differential diagnosis, prognosis, and indication of acute deterioration of IPF and so on.: Significant advances have been made in the role of biomarkers for IPF these years; however, current data indicate that a single biomarker is unlikely to have a transformative effect on clinical practice; therefore, the combined effect of various biomarkers can be considered to improve the accuracy of diagnosis and prognosis. Further research of biomarkers may provide new insights for the diagnosis, prognosis, and even therapy of IPF.
Topics: Biomarkers; Diagnosis, Differential; Humans; Idiopathic Pulmonary Fibrosis; Lung; Prognosis
PubMed: 32187497
DOI: 10.1080/17476348.2020.1745066 -
The European Respiratory Journal Apr 2024
Topics: Humans; Pulmonary Fibrosis; Pulmonary Emphysema; Emphysema
PubMed: 38575167
DOI: 10.1183/13993003.00353-2024 -
Biomolecules Mar 2023Pulmonary fibrosis (PF) is an interstitial lung disease characterized by the destruction of the pulmonary parenchyma caused by excessive extracellular matrix deposition.... (Review)
Review
Pulmonary fibrosis (PF) is an interstitial lung disease characterized by the destruction of the pulmonary parenchyma caused by excessive extracellular matrix deposition. Despite the well-known etiological factors such as senescence, aberrant epithelial cell and fibroblast activation, and chronic inflammation, PF has recently been recognized as a metabolic disease and abnormal lipid signature was observed both in serum and bronchoalveolar lavage fluid (BALF) of PF patients and mice PF model. Clinically, observational studies suggest a significant link between high-fat diet (HFD) and PF as manifested by high intake of saturated fatty acids (SFAs) and meat increases the risk of PF and mice lung fibrosis. However, the possible mechanisms between HFD and PF remain unclear. In the current review we emphasize the diversity effects of the epigenetic dysregulation induced by HFD on the fibrotic factors such as epithelial cell injury, abnormal fibroblast activation and chronic inflammation. Finally, we discuss the potential ways for patients to improve their conditions and emphasize the prospect of targeted therapy based on epigenetic regulation for scientific researchers or drug developers.
Topics: Animals; Mice; Pulmonary Fibrosis; Diet, High-Fat; Epigenesis, Genetic; Lung; Inflammation
PubMed: 36979493
DOI: 10.3390/biom13030558 -
International Journal of Chronic... 2023The comorbidity of pulmonary fibrosis and COPD/emphysema has garnered increasing attention. However, no bibliometric analysis of this comorbidity has been conducted thus...
OBJECTIVE
The comorbidity of pulmonary fibrosis and COPD/emphysema has garnered increasing attention. However, no bibliometric analysis of this comorbidity has been conducted thus far. This study aims to perform a bibliometric analysis to explore the current status and cutting-edge trends in the field, and to establish new directions for future research.
METHODS
Statistical computing, graphics, and data visualization tools such as VOSviewer, CiteSpace, Biblimatrix, and WPS Office were employed.
RESULTS
We identified a total of 1827 original articles and reviews on the comorbidity of pulmonary fibrosis and COPD/emphysema published between 2004 and 2023. There was an observed increasing trend in publications related to this comorbidity. The United States, Japan, and the United Kingdom were the countries with the highest contributions. Professor Athol Wells and the University of Groningen had the highest h-index and the most articles, respectively. Through cluster analysis of co-cited documents, we identified the top 17 major clusters. Keyword analysis predicted that NF-κB, oxidative stress, physical activity, and air pollution might be hot spots in this field in the future.
CONCLUSION
This bibliometric analysis demonstrates a continuous increasing trend in literature related to the comorbidity of pulmonary fibrosis and COPD/emphysema. The research hotspots and trends identified in this study provide a reference for in-depth research in this field, aiming to promote the development of the comorbidity of pulmonary fibrosis and COPD/emphysema.
Topics: Humans; Pulmonary Fibrosis; Pulmonary Disease, Chronic Obstructive; Comorbidity; Emphysema; Pulmonary Emphysema
PubMed: 37720874
DOI: 10.2147/COPD.S426763 -
Journal of Clinical Pharmacology Jul 2024Idiopathic pulmonary fibrosis (IPF) is a continuous, progressive, and lethal age-related respiratory disease. It is characterized by condensed and rigid lung tissue,... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a continuous, progressive, and lethal age-related respiratory disease. It is characterized by condensed and rigid lung tissue, which leads to a decline in the normal functioning of the lungs. The pathophysiology of IPF has still not been completely elucidated, so current strategies are lagging behind with respect to improving the condition of patients with IPF and increasing their survival rate. The desire for a better understanding of the pathobiology of IPF and its early detection has led to the identification of various biomarkers associated with IPF. The use of drugs such as pirfenidone and nintedanib as a safe and effective treatment alternative have marked a new chapter in the treatment of IPF. However, nonpharmacological therapies, involving long-term oxygen therapy, transplantation of the lungs, pulmonary rehabilitation, ventilation, and palliative care for cough and dyspnea, are still considered to be beneficial as supplementary methods for IPF therapy. A major risk factor for IPF is aging, with associated hallmarks such as telomere attrition, senescence, epigenetic drift, stem cell exhaustion, loss of proteostasis, and mitochondrial dysfunction. These are promising earmarks for the development of potential therapy for the disease. In this review, we have discussed current and emerging novel therapeutic strategies for IPF, especially for targets associated with age-related mechanisms.
Topics: Humans; Idiopathic Pulmonary Fibrosis; Indoles; Animals; Pyridones; Aging
PubMed: 38346921
DOI: 10.1002/jcph.2408 -
Experimental Gerontology Oct 2021Idiopathic pulmonary fibrosis (IPF) is a chronic lung fibrosing disease with high prevalence that has a prognosis worse than many cancers. There has been a recent influx... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a chronic lung fibrosing disease with high prevalence that has a prognosis worse than many cancers. There has been a recent influx of new observations aimed at explaining the mechanisms responsible for the initiation and progression of pulmonary fibrosis. However, despite this, the pathogenesis of the disease is largely unclear. Recent progress has been made in the characterization of specific pathologic and clinical features that have enhanced the understanding of pathologically activated molecular pathways during the onset and progression of IPF. This review highlights several of the advances that have been made and focus on the pathobiology of IPF. The work also details the different factors that are responsible for the disposition of the disease - these may be internal factors such as cellular mechanisms and genetic alterations, or they may be external factors from the environment. The changes that primarily occur in epithelial cells and fibroblasts that lead to the activation of profibrotic pathways are discussed in depth. Finally, a complete repertoire of the treatment therapies that have been used in the past as well as future medications and therapies is provided.
Topics: Epithelial Cells; Fibroblasts; Fibrosis; Humans; Idiopathic Pulmonary Fibrosis; Prognosis
PubMed: 34274426
DOI: 10.1016/j.exger.2021.111473 -
Seminars in Radiation Oncology Apr 2021Radiation-induced lung injury encompasses radiation-induced pneumonitis, inflammation of the lung which may manifest as a dose-limiting acute or subacute toxicity, and... (Review)
Review
Radiation-induced lung injury encompasses radiation-induced pneumonitis, inflammation of the lung which may manifest as a dose-limiting acute or subacute toxicity, and radiation-induced lung fibrosis, a late effect of lung exposure to radiation. This review aims to highlight developments in molecular radiation biology of radiation-induced lung injury and their implications in clinical practice.
Topics: Humans; Lung; Lung Injury; Pulmonary Fibrosis; Radiation Pneumonitis; Radiobiology
PubMed: 33610273
DOI: 10.1016/j.semradonc.2020.11.006 -
Expert Opinion on Investigational Drugs Dec 2021Lung injury in severe COVID-19 pneumonia can rapidly evolve to established pulmonary fibrosis, with prognostic implications in the acute phase of the disease and... (Review)
Review
INTRODUCTION
Lung injury in severe COVID-19 pneumonia can rapidly evolve to established pulmonary fibrosis, with prognostic implications in the acute phase of the disease and long-lasting impact on the quality of life of COVID-19 survivors. This is an emerging medical need, and it has been hypothesized that antifibrotic treatments could have a role in ameliorating the fibrotic process in the lungs of these patients.
AREAS COVERED
The safety and efficacy of available antifibrotic drugs (nintedanib and pirfenidone) and novel promising agents are being assessed in several ongoing clinical trials that were performed either in critically ill patients admitted to intensive care, or in discharged patients presenting fibrotic sequalae from COVID-19. Literature search was performed using Medline and Clinicaltrials.org databases (2001-2021).
EXPERT OPINION
Despite the strong rationale support the use of antifibrotic therapies in COVID-related fibrosis, there are several uncertainties regarding the timing for their introduction and the real risks/benefits ratio of antifibrotic treatment in the acute and the chronic phases of the disease. The findings of ongoing clinical trials and the long-term observation of longitudinal cohorts will eventually clarify the best management approach for these patients.
Topics: Animals; Antifibrotic Agents; COVID-19; Critical Illness; Humans; Indoles; Pulmonary Fibrosis; Pyridones
PubMed: 34842488
DOI: 10.1080/13543784.2021.2010188