Exploration of Medicine

Special Issue Topic

Lung Fibrosis—Models and Mechanisms

Submission Deadline: July 31, 2023

Guest Editor

Prof. Bernhard Ryffel E-Mail

Professor, INEM, UMR7355, CNRS, University of Orleans, Orleans, France

Research Keywords: mechanisms of inflammation, innate immune danger sensing, inflammasome activation, IL-33 and Th17/Th22 differentiation

About the Special Issue

The lung is a critical organ for the gas exchange and health. Chronic environmental exposures may cause injury of the respiratory barrier leading to inflammation, emphysema and progressive interstitial fibrosis leading respiratory failure. We will start with an overview of human fibrotic diseases and then address the following issues:
● Aerosol and systemic exposure to particles, smoke, allergens, chemicals, ozone, radiation viral, bacterial, parasite and helminth infection
● The clinical perspectives of COPD, rodent and in vitro models, predictive for COPD?
● Idiopathic pulmonary fibrosis IPF and preclinical models
● Molecular mechanisms of fibrosis progression and cell death pathways
● Role of TLR, Inflammasome, DNA sensing and cross-talk of pathways
● InflammAging, senescence and autophagy
● Inflammatory cytokine such TNF and IL-1 family member, growth factors…
● Contribution of intestinal microbiota and metabolism such as SCFA, tryptophan serotonin…
● Prevention and therapy, new therapeutic targets and drug candidates

Keywords: TNF, IL-1, growth factors, NLRP, TLR, autophagy, senescence, pollution, microbiome, metabolites, disease models

Call for Papers

Published Articles

Open Access

Perspective

Utility of fibroblasts derived from broncho-alveolar lavage of patients with idiopathic pulmonary fibrosis or related disorders to develop in vitro models
Broncho-alveolar lavage (BAL) represents a safe tool for the differential diagnosis of various pulmonary fibrotic diseases. Idiopathic pulmonary fibrosis (IPF) belongs to a heterogeneous group of di [...] Read more.

Broncho-alveolar lavage (BAL) represents a safe tool for the differential diagnosis of various pulmonary fibrotic diseases. Idiopathic pulmonary fibrosis (IPF) belongs to a heterogeneous group of diseases, interstitial lung disease (ILD), presenting a progressive impairment of pulmonary functions. IPF is characterized by the excessive accumulation of extracellular matrix (ECM) in the alveolar parenchyma that may lead to irreversible pulmonary remodeling. Although the exact pathogenetic mechanisms leading to IPF development are still unclear it has been demonstrated that fibroblasts differentiating toward myofibroblasts are the major actors involved in this process. The possibility of obtaining and expanding fibroblasts from the BAL of ILD patients for research purposes has been recently explored. This approach is discussed here as a reliable chance, helpful to advance the scientific community knowledge and to devise two- and three-dimensional (2D/3D) pre-clinical in vitro models of these diseases, further overcoming technical and ethical concerns related to the use of fibroblasts derived from tissue biopsy.

Paolo Giannoni ... Daniela de Totero

Published: August 31, 2023 Explor Med. 2023;4:461–470
DOI: https://doi.org/10.37349/emed.2023.00156

Full Text

PDF

View:245

Download:10

Times Cited: 0

Broncho-alveolar lavage (BAL) represents a safe tool for the differential diagnosis of various pulmonary fibrotic diseases. Idiopathic pulmonary fibrosis (IPF) belongs to a heterogeneous group of diseases, interstitial lung disease (ILD), presenting a progressive impairment of pulmonary functions. IPF is characterized by the excessive accumulation of extracellular matrix (ECM) in the alveolar parenchyma that may lead to irreversible pulmonary remodeling. Although the exact pathogenetic mechanisms leading to IPF development are still unclear it has been demonstrated that fibroblasts differentiating toward myofibroblasts are the major actors involved in this process. The possibility of obtaining and expanding fibroblasts from the BAL of ILD patients for research purposes has been recently explored. This approach is discussed here as a reliable chance, helpful to advance the scientific community knowledge and to devise two- and three-dimensional (2D/3D) pre-clinical in vitro models of these diseases, further overcoming technical and ethical concerns related to the use of fibroblasts derived from tissue biopsy.

Open Access

Original Article

Mechanistic approaching study in COVID-19 patients treated with high doses of vitamin D
Aim: To evaluate angiotensin II (Ang II) and Ang-(1-7) levels and the cytokine profile in patients hospitalized with mild coronavirus disease 2019 (COVID-19) and contrast them with patients with identical clinical conditions but t [...] Read more.

Aim:

To evaluate angiotensin II (Ang II) and Ang-(1-7) levels and the cytokine profile in patients hospitalized with mild coronavirus disease 2019 (COVID-19) and contrast them with patients with identical clinical conditions but treated with high doses of vitamin D (vitD).

Methods:

From the 218 patients recruited (ClinicalTrials.gov NCT04411446), 16 participated in this sub-study and were randomized to a single oral dose of 500,000 IU vitD (n = 10) or placebo (n = 6). Plasmatic Ang II and Ang-(1-7) levels were determined by radioimmunoassay and interleukins (ILs) 1, 6, 8, and 10 and tumor necrosis factor alpha (TNF-α) by enzyme-linked immunosorbent assay before and after treatment. Parallel, serum 25-hydroxyvitamin D3 (25-OH vitD) concentrations as vitD status was measured by a chemiluminescence immunoassay.

Results:

A trend towards an increase in Ang-(1-7) and a decrease in Ang II levels were observed in placebo- and vitD-treated COVID-19 patients compared to baseline values. There was no difference in Ang II and Ang-(1-7) levels between placebo- and vitD-treated COVID-19 patients. Similar results were obtained with ILs profile. COVID-19 patients showed an increase in the protective component of the RAS which was not improved by vitD treatment.

Conclusions:

VitD did not improve RAS disbalance in COVID-19. Notwithstanding, the authors visualize that acute treatment with high doses of vitD may show a trend to a decline in inflammatory ILs and an increase in protective markers. Finally, the authors would like to highlight the limitations of this preliminary study, namely the small number of patients and the use of a large single bolus dose of vitD rather than lower daily doses for extended periods with prolonged follow-up times. All these factors need special consideration in the designs of new vitD supplementation trials. All these factors need special consideration in the designs of new vitD supplementation trials (ClinicalTrials.gov identifier: NCT04411446).

Mauro G. Silva ... Walter Manucha

Published: April 26, 2023 Explor Med. 2023;4:246–253
DOI: https://doi.org/10.37349/emed.2023.00137

Full Text

PDF

View:464

Download:20

Times Cited: 0

Aim:

To evaluate angiotensin II (Ang II) and Ang-(1-7) levels and the cytokine profile in patients hospitalized with mild coronavirus disease 2019 (COVID-19) and contrast them with patients with identical clinical conditions but treated with high doses of vitamin D (vitD).

Methods:

From the 218 patients recruited (ClinicalTrials.gov NCT04411446), 16 participated in this sub-study and were randomized to a single oral dose of 500,000 IU vitD (n = 10) or placebo (n = 6). Plasmatic Ang II and Ang-(1-7) levels were determined by radioimmunoassay and interleukins (ILs) 1, 6, 8, and 10 and tumor necrosis factor alpha (TNF-α) by enzyme-linked immunosorbent assay before and after treatment. Parallel, serum 25-hydroxyvitamin D3 (25-OH vitD) concentrations as vitD status was measured by a chemiluminescence immunoassay.

Results:

A trend towards an increase in Ang-(1-7) and a decrease in Ang II levels were observed in placebo- and vitD-treated COVID-19 patients compared to baseline values. There was no difference in Ang II and Ang-(1-7) levels between placebo- and vitD-treated COVID-19 patients. Similar results were obtained with ILs profile. COVID-19 patients showed an increase in the protective component of the RAS which was not improved by vitD treatment.

Conclusions:

VitD did not improve RAS disbalance in COVID-19. Notwithstanding, the authors visualize that acute treatment with high doses of vitD may show a trend to a decline in inflammatory ILs and an increase in protective markers. Finally, the authors would like to highlight the limitations of this preliminary study, namely the small number of patients and the use of a large single bolus dose of vitD rather than lower daily doses for extended periods with prolonged follow-up times. All these factors need special consideration in the designs of new vitD supplementation trials. All these factors need special consideration in the designs of new vitD supplementation trials (ClinicalTrials.gov identifier: NCT04411446).

Guest Editor

About the Special Issue

Call for Papers

Published Articles

Aim:

Methods:

Results:

Conclusions:

Aim:

Methods:

Results:

Conclusions: