International Journal of Molecular Sciences

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Dear Colleagues,

Both chronic and acute infections play a significant role in the pathogenesis and clinical course of chronic obstructive pulmonary disease (COPD) and both cystic fibrosis (CF) and non-CF bronchiectasis. There is also specific evidence that chronic infection, even in the absence of acute infection, has an influence on the manifestations and disease course. The infections found in COPD, CF, and bronchiectasis share a number of clinical similarities, the most striking of which are bacterial persistence despite the use of antibiotics and antibiotic resistance.

In the last two decades, antibiotic resistance rate has increased dramatically and poses serious threats for patients and the public health. There are different reasons for this increase in resistance, but the overuse of antibiotics in the community is certainly the most prominent. On the other hand, chronic use of antibiotics in chronic diseases like COPD, CF and bronchiectasis is also potentially associated to an increase in MDR pathogens. During the last decade, a growing interest has been raised in evaluating nontuberculous mycobacteria’s role in chronic respiratory diseases like bronchiectasis.

Prof. Dr. Francesco B. Blasi
Guest Editor

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15 pages, 2207 KiB

Open AccessArticle

Apalutamide Prevents SARS-CoV-2 Infection in Lung Epithelial Cells and in Human Nasal Epithelial Cells

by Amene Majidipur, Margot Morin-Dewaele, Jeanne Gaspar Lopes, Francois Berry, Julien Fouchet, Sophie Bartier, Anais Dufros Duval, Pascale Soyeux, Eric Huet, Bruno Louis, André Coste, Émilie Béquignon, Carolina Saldana, Philippe Le Corvoisier, Damien Destouches, Jean-Michel Pawlotsky, Alexandre de la Taille, Francis Vacherot, Patrice Bruscella and Virginie Firlej

Int. J. Mol. Sci. 2023, 24(4), 3288; https://doi.org/10.3390/ijms24043288 - 07 Feb 2023

Cited by 1 | Viewed by 2431

Abstract

In early 2020, the novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, and rapidly propagated worldwide causing a global health emergency. SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) protein for cell entry, followed by proteolytic cleavage of the Spike (S) protein by the transmembrane serine protease 2 (TMPRSS2), allowing fusion of the viral and cellular membranes. Interestingly, TMPRSS2 is a key regulator in prostate cancer (PCa) progression which is regulated by androgen receptor (AR) signaling. Our hypothesis is that the AR signaling may regulate the expression of TMPRSS2 in human respiratory cells and thus influence the membrane fusion entry pathway of SARS-CoV-2. We show here that TMPRSS2 and AR are expressed in Calu-3 lung cells. In this cell line, TMPRSS2 expression is regulated by androgens. Finally, pre-treatment with anti-androgen drugs such as apalutamide significantly reduced SARS-CoV-2 entry and infection in Calu-3 lung cells but also in primary human nasal epithelial cells. Altogether, these data provide strong evidence to support the use of apalutamide as a treatment option for the PCa population vulnerable to severe COVID-19. Full article

(This article belongs to the Special Issue Lung Diseases: Chronic Respiratory Infections 2.0)

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21 pages, 3978 KiB

Open AccessArticle

Nintedanib-αVβ6 Integrin Ligand Conjugates Reduce TGFβ-Induced EMT in Human Non-Small Cell Lung Cancer

by Elena Andreucci, Kelly Bugatti, Silvia Peppicelli, Jessica Ruzzolini, Matteo Lulli, Lido Calorini, Lucia Battistini, Franca Zanardi, Andrea Sartori and Francesca Bianchini

Int. J. Mol. Sci. 2023, 24(2), 1475; https://doi.org/10.3390/ijms24021475 - 12 Jan 2023

Viewed by 2458

Abstract

Growth factors and cytokines released in the lung cancer microenvironment promote an epithelial-to-mesenchymal transition (EMT) that sustains the progression of neoplastic diseases. TGFβ is one of the most powerful inducers of this transition, as it induces overexpression of the fibronectin receptor, αvβ6 integrin, in cancer cells which, in turn, is strongly associated with EMT. Thus, αvβ6 integrin receptors may be exploited as a target for the selective delivery of anti-tumor agents. We introduce three novel synthesized conjugates, in which a selective αvβ6 receptor ligand is linked to nintedanib, a potent kinase inhibitor used to treat advanced adenocarcinoma lung cancer in clinics. The αvβ6 integrin ligand directs nintedanib activity to the target cells of the tumor microenvironment, avoiding the onset of negative side effects in normal cells. We found that the three conjugates inhibit the adhesion of cancer cells to fibronectin in a concentration-dependent manner and that αvβ6-expressing cells internalized the conjugated compounds, thus permitting nintedanib to inhibit 2D and 3D cancer cell growth and suppress the clonogenic ability of the EMT phenotype as well as intervening in other aspects associated with the EMT transition. These results highlight αvβ6 receptors as privileged access points for dual-targeting molecular conjugates engaged in an efficient and precise strategy against non-small cell lung cancer. Full article

(This article belongs to the Special Issue Lung Diseases: Chronic Respiratory Infections 2.0)

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