GPER Activation Attenuates Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome Sex-Dependently and Inhibits Alveolar Macrophage Activation

Background: Acute respiratory distress syndrome (ARDS), a common and critical disease, is clinically characterized by uncontrolled inflammation and alveolar-capillary barrier disruption. Estrogen can reportedly alleviate ARDS caused by numerous insults in mice. Moreover, the estradiol receptors α, not β,participated in E2-induced attenuation of ARDS. But the role of another estradiol receptor, G protein-coupled estradiol receptor 1 (GPER1) in ARDS are not undertood. This study is aimed to investigate the effect of GPER activation on LPS-induced ARDS in mice.Methods: Female mice were randomly subjected to bilateral ovarectomy (OVX) or sham surgery two weeks before lung injury. The GPER-selective agonist G1 or vehicle were intraperitoneally injected 0.5 h before intratracheal administration of LPS or phosphate-buffered saline in male and female mice. After 24 h, mice were sacrificed to collect blood, bronchoalveolar lavage fluid (BALF), and lung tissue. Histological injury and inflammatory cell infiltration in lung tissue, as well as cytokine and protein concentrations in BALF were determined. In vitro experiments were also performed on alveolar macrophages (MH-S cells) to investigate the effect of GPER activation on LPS-induced inflammatory responses.Results: Activation of GPER by G1 administration significantly ameliorated lung pathological damage, attenuated alveolar capillary barrier destruction, inhibited recruitment of inflammatory cells into alveoli, and decreased concentrations of the pro-inflammatory factors tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in BALF of LPS-administered male and OVX female mice, but not intact female mice. In vitro experiments demonstrated that G1 pretreatment significantly inhibited LPS-mediated increases of TNF-α, IL-6, and MIP2 in a dose-dependent manner.Conclusions: These results demonstrated that GPER activation attenuated lung injury of male and OVX female mice by inhibiting the inflammatory response of alveolar macrophages.

A preliminary exploration of the micro-scale behaviour of capillary barrier effect using microfluidics

Capillary barrier effect (CBE) is employed in a large number of geotechnical applications to decrease deep percolation or increase slope stability. However, the micro-scale behaviour of CBE is rarely investigated, and thus hampers the scientific design of capillary barrier systems. This study uses microfluidics to explore the micro-scale behaviour of CBE. Capillarity-driven water flow processes from fine to coarse porous media with different pore topologies and sizes were performed and analysed. The experimental results demonstrate that the basic physics of CBE is the preferential water movement into the fine porous media due to the larger capillarity. The effects of CBE on water flow processes can be identified as delaying the occurrence of breakthrough into the coarse porous media and increasing the water storage of the fine porous media. The CBE can impede the increase of the normalized length and decrease the normalized width of the water front, suggesting that the two normalized parameters are potential indicators to assess the performance of CBE at micro scale. CBE can be formed in square and honeycomb networks with the ratio of coarse to fine pore throat width larger than 2.0 when gravity is neglected, and its performance can be affected by pore topology and size.

Extracellular Vesicles and Alveolar Epithelial-Capillary Barrier Disruption in Acute Respiratory Distress Syndrome: Pathophysiological Role and Therapeutic Potential

Extracellular vesicles (EVs) mediate intercellular communication by transferring genetic material, proteins and organelles between different cells types in both health and disease. Recent evidence suggests that these vesicles, more than simply diagnostic markers, are key mediators of the pathophysiology of acute respiratory distress syndrome (ARDS) and other lung diseases. In this review, we will discuss the contribution of EVs released by pulmonary structural cells (alveolar epithelial and endothelial cells) and immune cells in these diseases, with particular attention to their ability to modulate inflammation and alveolar-capillary barrier disruption, a hallmark of ARDS. EVs also offer a unique opportunity to develop new therapeutics for the treatment of ARDS. Evidences supporting the ability of stem cell-derived EVs to attenuate the lung injury and ongoing strategies to improve their therapeutic potential are also discussed.

Experimental evaluation of salinity geosynthetics capillary barriers

This paper explores the transient upward flow of saline water in one-dimensional soil and soil-geosynthetics columns to evaluate preventive measures to mitigate salinity rise. Unsaturated soil concepts are utilised to elucidate the salinity movement through geotextile and geocomposite drain interfaces. The presence of a geotextile layer slowed down the capillary rise of the saline water. However, it did not prevent the breakthrough of the saline water due to the hydrophilicity of the geotextile and the suction at the geotextile base being close to the geotextile's water entry suction value. In contrast, using a geocomposite drain mitigated the upward saline wetting front. It acted as a salinity capillary barrier due to the initial hydrophobicity of its geotextile component and the air gap present in the geonet core.

Construction And Test of An Instrumented 2D Channel With Rainfall And Insolation Control.

This paper presents the construction and testing of a large instrumented 2D channel for the simulation of the performance of compacted barriers under controlled conditions of insolation and rainfall. Details of the main apparatus devices and capabilities and the results of a long-term test performed on a capillary barrier (CB) are presented. The performed test aimed to simulate the CB behavior over a period of one year in typical semi-arid conditions. The channel behavior was considered very promising with its components functioning as expected and providing the desired information. Concerning the CB performance, it is shown that the upper clayey layer of soil presented undesirable shrinkage cracks that impacted the CB performance, mainly at the end of the period of evaluation. The obtained results point to the need to use of silty or low plasticity clayey soils in the CB design, despite the higher expected values of hydraulic conductivity, as well as the adoption of layers thicker than usual in order to preserve the integrity of the clayey soil near the interface with the bottom coarse soil layer.

Gene transfer of MRCKα rescues lipopolysaccharide-induced acute lung injury by restoring alveolar capillary barrier function

Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) is characterized by alveolar edema accumulation with reduced alveolar fluid clearance (AFC), alveolar-capillary barrier disruption, and substantial inflammation, all leading to acute respiratory failure. Enhancing AFC has long been considered one of the primary therapeutic goals in gene therapy treatments for ARDS. We previously showed that electroporation-mediated gene delivery of the Na+, K+-ATPase β1 subunit not only increased AFC, but also restored alveolar barrier function through upregulation of tight junction proteins, leading to treatment of LPS-induced ALI in mice. We identified MRCKα as an interaction partner of β1 which mediates this upregulation in cultured alveolar epithelial cells. In this study, we investigate whether electroporation-mediated gene transfer of MRCKα to the lungs can attenuate LPS-induced acute lung injury in vivo. Compared to mice that received a non-expressing plasmid, those receiving the MRCKα plasmid showed attenuated LPS-increased pulmonary edema and lung leakage, restored tight junction protein expression, and improved overall outcomes. Interestingly, gene transfer of MRCKα did not alter AFC rates. Studies using both cultured microvascular endothelial cells and mice suggest that β1 and MRCKα upregulate junctional complexes in both alveolar epithelial and capillary endothelial cells, and that one or both barriers may be positively affected by our approach. Our data support a model of treatment for ALI/ARDS in which improvement of alveolar-capillary barrier function alone may be of more benefit than improvement of alveolar fluid clearance.

Valorisation of Partially Oxidized Tailings in a Cover System to Reclaim an Old Acid Generating Mine Site

The reclamation of acid-generating mine tailings typically involves building cover systems to limit interactions with water or oxygen. The choice of cover materials is critical to ensure long-term performance, and partly determines the environmental footprint of the reclamation strategy. The objective of this research was to evaluate if tailings pre-oxidized on-site could be used in cover systems. Column experiments were performed to assess the effectiveness of a cover with capillary barrier effects (CCBE), where the moisture retention layer (MRL) was made of pre-oxidized tailings with little to no remaining sulfides (LS tailings). The columns were submitted to regular wetting and drying cycles, and their hydrological and geochemical behaviour was monitored for 510 days. The LS tailings showed satisfying hydrological properties as an MRL and remained saturated throughout the test. The concentrations of Cu in the drainage decreased by more than two orders of magnitude compared to non-covered tailings. In addition, the pH increased by nearly one unit compared to the control column, and Fe and S concentrations decreased by around 50%. Despite these improvements, the leachate water remained acidic and contaminated, indicating that acid drainage continued to be generated despite a hydrologically efficient CCBE.