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Article
| Open Access
Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity
There is a need for an accurate measure of pulmonary oxygenation function that can be used as an intermediate endpoint in pragmatic clinical trials, to increase statistical power and efficiency. Here, the authors show that the S/F94, a modification of the S/F ratio, is a simple, meaningful and effective intermediate outcome measure.
- Maaike C. Swets
- , Steven Kerr
- & J. Kenneth Baillie
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Article
| Open Access
Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage
Macrophages are increasingly recognized as key drivers of lung damage in acute pneumonia including COVID-19. Here, the authors report on a first-in-class, inhalable, carbohydrate-coupled microRNA-inhibitor for selective targeting of macrophages and that prevents pulmonary hyperinflammation.
- Christina Beck
- , Deepak Ramanujam
- & Stefan Engelhardt
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Article
| Open Access
Circadian clock molecule REV-ERBα regulates lung fibrotic progression through collagen stabilization
The molecular clock REV-ERBα regulates lung injury during fibrosis, but the role of REV-ERBα in fibrogenesis remains unknown. Here, the authors show that REV-ERBα interacts with the lysyl oxidase-collagen axis during fibrogenesis and demonstrate the therapeutic potential of Rev-erbα agonist against lung fibrosis.
- Qixin Wang
- , Isaac Kirubakaran Sundar
- & Irfan Rahman
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Article
| Open Access
Retinoids stored locally in the lung are required to attenuate the severity of acute lung injury in male mice
Retinoids can act as transcriptional regulators to regulate cell proliferation, differentiation, and other processes. Here, the authors show that uncompromised vitamin A (retinoid) metabolism and signaling in alveolar lipofibroblasts, endothelial and epithelial cells are required to lessen the severity of an acute inflammatory challenge in adult mouse lungs.
- Igor O. Shmarakov
- , Galina A. Gusarova
- & William S. Blaner
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Article
| Open Access
Locally organised and activated Fth1hi neutrophils aggravate inflammation of acute lung injury in an IL-10-dependent manner
Acute respiratory distress syndrome (ARDS) is an acute pulmonary disease involving neutrophils. Here the authors characterise lung neutrophil infiltration during ARDS and show that there are neutrophils with different function and transcriptional profile which are regulated by IL-10.
- Kun Wang
- , Muyun Wang
- & Wei Gao
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Article
| Open Access
Stratifin as a novel diagnostic biomarker in serum for diffuse alveolar damage
No reliable serum biomarker for diffuse alveolar damage, a poor prognosis subtype of drug-induced interstitial lung disease, is currently available. Here, the authors show stratifin/14-3-3σ in serum is a promising biomarker for diagnosis of this type of disease.
- Noriaki Arakawa
- , Atsuhito Ushiki
- & Masayuki Hanaoka
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Article
| Open Access
The mitochondrial calcium uniporter of pulmonary type 2 cells determines severity of acute lung injury
Acute lung injury caused by inhalation of pathogens leads to mortality, but the mechanisms are unclear. Here, the authors show in mice that that loss of the mitochondrial calcium uniporter (MCU) of alveolar type 2 cells (AT2) impaired mitochondrial Ca2+ buffering and surfactant secretion, and increased mortality, in response to LPS instillation, suggesting the MCU as a potential therapeutic target in ALI.
- Mohammad Naimul Islam
- , Galina A. Gusarova
- & Jahar Bhattacharya
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Article
| Open Access
Host lung microbiota promotes malaria-associated acute respiratory distress syndrome
The reasons why malaria manifests with a variety of well-recognized clinical phenotypes remain poorly understood. Here, using distinct rodent models, the authors reveal that the microbiota colonizing the lung promotes respiratory distress syndrome and mortality during malaria infections.
- Debanjan Mukherjee
- , Ângelo Ferreira Chora
- & Maria M. Mota
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Article
| Open Access
ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury
Endogenous ACE2 is a receptor for SARS-CoV-2 and a recombinant soluble ACE2 protein can inhibit SARS-CoV-2 infection acting as a decoy. Here the authors show that B38-CAP, an ACE2-like enzyme but not a decoy for the virus, is protective against SARS-CoV-2-induced lung injury in animal models.
- Tomokazu Yamaguchi
- , Midori Hoshizaki
- & Keiji Kuba
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Article
| Open Access
Severe T cell hyporeactivity in ventilated COVID-19 patients correlates with prolonged virus persistence and poor outcomes
Perturbed T cell responses and disturbed cytokine secretion have been shown during SARS-CoV2 infection in patients. Here the authors show reduced polyclonal T cell activity in COVID-19 patients that is caused by plasma factors and linked to poor prognosis and viral persistence.
- Kerstin Renner
- , Tobias Schwittay
- & Matthias Mack
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Article
| Open Access
Targeting the deubiquitinase STAMBP inhibits NALP7 inflammasome activity
How NALP7 inflammasome formation is regulated is unclear. Here the authors show that STAMBP prevents lysosomal degradation of NALP7 and present BC-1471 as a potential therapeutic STAMBP inhibitor, showing it can reduce TLR-induced IL-1β production.
- Joseph S. Bednash
- , Nathaniel Weathington
- & Rama K. Mallampalli
Longitudinal multicompartment characterization of host-microbiota interactions in patients with acute respiratory failure