Despite the central importance of the respiratory system, the exact mechanisms governing lung repair after severe injury remain unclear. The notion that alveolar type 2 cells (AT2s) self-renew and differentiate into alveolar type 1 cells (AT1s) does not fully encompass scenarios where these progenitors are severely affected by disease, e.g., H1N1 influenza or SARS-CoV-2 (COVID-19). Intrapulmonary p63 + progenitor cells, a rare cell type in mice but potentially encompassing more numerous classic basal cells in humans, are activated in such severe injury settings, proliferating and migrating into the injured alveolar parenchyma, providing a short-term “emergency” benefit. While the fate of these cells is controversial, most studies indicate that they represent a maladaptive repair pathway with a fate restriction toward airway cell types, rarely differentiating into AT2 or AT1 cells. Here, we discuss the role of intrapulmonary basal-like p63 + cells in alveolar regeneration and suggest a unified model to guide future studies.

Acute respiratory distress syndrome is associated with a robust inflammatory response that damages the vascular endothelium, impairing gas exchange. While restoration of microcapillaries is critical to avoid mortality, therapeutic targeting of this process requires a greater understanding of endothelial repair mechanisms. Here, we demonstrate that lung endothelium possesses substantial regenerative capacity and lineage tracing reveals that native endothelium is the source of vascular repair after influenza injury. Ablation of chicken ovalbumin upstream promoter–transcription factor 2 (COUP-TF2) (Nr2f2), a transcription factor implicated in developmental angiogenesis, reduced endothelial proliferation, exacerbating viral lung injury in vivo. In vitro, COUP-TF2 regulates proliferation and migration through activation of cyclin D1 and neuropilin 1. Upon influenza injury, nuclear factor κB suppresses COUP-TF2, but surviving endothelial cells ultimately reestablish vascular homeostasis dependent on restoration of COUP-TF2. Therefore, stabilization of COUP-TF2 may represent a therapeutic strategy to enhance recovery from pathogens, including H1N1 influenza and SARS-CoV-2.

While the lung bears significant regenerative capacity, severe viral pneumonia can chronically impair lung function by triggering dysplastic remodeling. The connection between these enduring changes and chronic disease remains poorly understood. We recently described the emergence of tuft cells within Krt5+ dysplastic regions after influenza injury. Using bulk and single cell transcriptomics, we characterized and delineated multiple distinct tuft cell populations that arise following influenza clearance. Distinct from intestinal tuft cells which rely on Type 2 immune signals for their expansion, neither IL-25 nor IL-4ra signaling are required to drive tuft cell development in dysplastic/injured lungs. In addition, tuft cell expansion occurred independently of type I or type III interferon signalling. Furthermore, tuft cells were also observed upon bleomycin injury, suggesting that their development may be a general response to severe lung injury. While intestinal tuft cells promote growth and differentiation of surrounding epithelial cells, in the lungs of tuft cell deficient mice, Krt5+ dysplasia still occurs, goblet cell production is unchanged, and there remains no appreciable contribution of Krt5+ cells into more regionally appropriate alveolar Type 2 cells. Together, these findings highlight unexpected differences in signals necessary for murine lung tuft cell amplification and establish a framework for future elucidation of tuft cell functions in pulmonary health and disease.

Angiotensin II is a key regulator of blood pressure and cardiovascular function in mammals. The conversion of angiotensin into its active form is carried out by Angiotensin I-Converting Enzyme (ACE). The measurement of ACE concentration in plasma or serum, its enzymatic activity, and the correlation between an insertion/deletion (I/D) genetic polymorphism of the ACE gene have been investigated as possible indicators of superior athletic performance in humans. In this context, other indicators of superior adaptation to exercise resulting in better athletic performance (such as ventricular hypertrophy, VO2 max, and competition results) were mostly used to study the association between ACE I/D polymorphism and improved performance. Despite the fact that the existing literature presents little consensus, there is sufficient scientific evidence to warrant further investigation on the usage of ACE activity and the I/D ACE gene polymorphism as biomarkers of superior athletic performance in humans of specific ethnicities or in athletes involved in certain sports. In this sense, a biomarker would be a substance or genetic component that could be measured to provide a degree of certainty, or an indication, of the presence of a certain trait or characteristic that would be beneficial to the athlete’s performance. Difficulties in interpreting and comparing the results of scientific research on the topic arise from dissimilar protocols and variation in study design. This review aims to investigate the current literature on the use of ACE I/D polymorphism as a biomarker of performance in humans through the comparison of scientific publications.

Perfil citológico e influência da idade no lavado broncoalveolar de equinos sadios e com doença inflamatória de vias aéreas assintomática were, respectively: 56.9% and 48.0% macrophages, 37.2% and 40.0% lymphocytes, 3.3% and 7.1% neutrophils, 1.7% and 1.4% mast cells, 0.3% and 0.7% eosinophils; 0,5% and 0.4% epithelial cells. When Palavras-chave: equino, doença inflamatória das vias aéreas, citologia broncoalveolar. ABSTRACT Pulmonary inflammatory diseases have been observed in equine since their domestication. Non-infectious disease processes of the lower airways are amongst the most important diseases of the equine respiratory tract. This study aims to determine the cytology profile and effect of age on the evaluation of equine bronchoalveolar lavage (BAL) obtained from healthy animals and from horses with asymptomatic inflammatory airway disease (IAD). Thirty two horses, including

Platelet rich plasma (PRP) is an autologous biological product harvested by consecutive centrifugations of whole blood and separation of plasma in a stepwise protocol. PRP has been successfully used to stimulate healing in orthopedic and dermatological conditions, both in humans and animals. The principle is the fact that α- granules inside platelets contain a high concentration of growth factors, that once released can interfere with cellular communication and speed up healing. Standardization of PRP requires establishing a gold standard for the preparation and evaluation of the product, especially considering that platelet concentration and, therefore, growth factor concentration, might vary due to a number of variables. Factors such as age, gender, race or breed, and immune status of the patient might interfere with PRP quality and with treatment results, although little is known about such interferences. This research investigated the effect of breed/species and gender in platelet concentration in autologous PRP from horses and mules. The results demonstrate that Quarter Horses provided PRP with the greatest amount of platelets, although mules had a higher concentration percentages in relation to the initial platelet counts.

Angiotensin-I converting enzyme (ACE) is a key regulator of blood pressure, electrolytes and fluid homeostasis through conversion of angiotensin I into angiotensin II. Recently, a genetic polymorphism of the ACE gene, which accounts for 47% of the variation of ACE activity in blood, has been advocated as a biomarker of athletic aptitude. Different methods of analysis and determination of ACE activity in plasma have been used in human and equine research without a consensus of a "gold standard" method. Different methods have often been used interchangeably or cited as being comparable in the existing literature; however, the actual agreement between assays has not been investigated. Therefore, in this study, we evaluated the level of agreement between three different assays using equine plasma obtained from 29 horses. Two spectrophotometric assays using Furylacryloyl-phenylalanyl-glycyl-glycine as substrate and one fluorimetric assay utilizing o-aminobenzoic acid-FRK-(Dnp)P-OH were employed. The results revealed that the measurements from the different assays were not in agreement, indicating that the methods should not be used interchangeably for measurement of equine ACE activity. Rather, a single method of analysis should be adopted to achieve comparable results and critical appraisal of the literature is needed when attempting to compare results obtained from different assays.

Objective: R-spondin 2 (RSPO2) is required for lung morphogenesis, activates Wnt signaling, and is upregulated in idiopathic lung fibrosis. Our objective was to investigate whether RSPO2 is similarly important in homeostasis of the adult lung. While investigating the characteristics of bronchoalveolar lavage in RSPO2-deficient (RSPO2 −/−) mice, we observed unexpected changes in neutrophil homeostasis and vascular permeability when compared to control (RSPO2 +/+) mice at baseline. Here we quantify these observations to explore how tonic RSPO2 expression impacts lung homeostasis. Results: Quantitative PCR (qPCR) analysis demonstrated significantly elevated myeloperoxidase (MPO) expression in bronchoalveolar lavage fluid (BALF) cells from RSPO2 −/− mice. Likewise, immunocytochemical (ICC) analysis demonstrated significantly more MPO+ cells in BALF from RSPO2 −/− mice compared to controls, confirming the increase of infiltrated neutrophils. We then assessed lung permeability/barrier disruption via Fluorescein Isothiocyanate (FITC)dextran instillation and found a significantly higher dextran concentration in the plasma of RSPO2 −/− mice compared to identically treated RSPO2 +/+ mice. These data demonstrate that RSPO2 may be crucial for blood-gas barrier integrity and can limit neutrophil migration from circulation into alveolar spaces associated with increased lung permeability and/or barrier disruption. This study indicates that additional research is needed to evaluate RSPO2 in scenarios characterized by pulmonary edema or neutrophilia.