Biology subjects

Sapin, V.

Publications and source records attributed to Sapin, V..

3 recordsLinked to original sources

bioRxiv2022

Spatial distribution and physicochemical properties of respirable volcanic ash from the 16-17 August 2006 Tungurahua eruption (Ecuador), and alveolar epithelium response in-vitro

BackgroundTungurahua volcano (Ecuador) intermittently emitted ash between 1999 and 2016, enduringly affecting the surrounding rural area and its population, but its health impact remains poorly documented. ObjectivesWe aim at assessing the respiratory health hazard posed by the 16-17 August 2006 most intense eruptive phase of Tungurahua. MethodsBased on detailed field surveys and grain size analyses, we mapped the spatial distribution of the health-relevant ash size fractions produced by the eruption in the area impacted by ash fallout. We used Scanning Electron Microscopy and Raman Spectroscopy to quantify the mineralogy, composition, surface texture and morphology of a respirable ash sample isolated by aerodynamic separation. The cytotoxicity and pro-inflammatory potential of this respirable ash towards lung tissues was assessed in-vitro using A549 alveolar epithelial cells, by Electron Microscopy and biochemical assays (LDH assay, RT-qPCR, multiplex immunoassays). ResultsThe eruption produced a high amount of inhalable and respirable ash (12.0-0.04 kg/m2 of sub-10 {micro}m and 5.3-0.02 kg/m2 of sub-4 {micro}m ash deposited). Their abundance and proportion vary greatly across the deposit within the first 20 km from the volcano. The respirable ash is characteristic of an andesitic magma and no crystalline silica is detected. Morphological features and surface textures are complex and highly variable, with few fibres observed. In-vitro experiments show that respirable volcanic ash are internalized by A549 cells and processed in the endosomal pathway, causing little cell damage, but some changes in cell morphology and membrane texture. The ash trigger a weak pro-inflammatory response. DiscussionThese data provide the first understanding of the respirable ash hazard near Tungurahua, and the extent to which it varies spatially in a fallout deposit. Given the long exposure duration of the surrounding population, the chronic effects of this inhalable, weakly bio-reactive ash on health could be further investigated.

ecology↗

bioRxiv2021

TLR4 regulation in human fetal membranes as an explicative mechanism of a pathological preterm case.

The integrity of human fetal membranes is crucial for harmonious fetal development throughout pregnancy. Their premature rupture is often the consequence of a physiological phenomenon previously exacerbated. Beyond all biological processes implied, inflammation is of primary importance and is qualified as "sterile" at the end of pregnancy. Complementary methylomic and transcriptomic strategies on amnion and choriodecidua explants taken from the altered (cervix zone) and intact fetal membranes at term and before labor were used in this study. By cross-analyzing genome-wide studies strengthened by in vitro experiments, we deciphered how the expression of Toll-like receptor 4 (TLR4), a well-known actor of pathological fetal membrane rupture, is controlled. Indeed, it is differentially regulated in the altered zone and between both layers by a dual mechanism: 1) the methylation of TLR4 and miRNA promoters and 2) targeting by miRNA (let-7a-2 and miR-125b-1) acting on the 3-UTR of TLR4. Consequently, this study demonstrates that a fine regulation of TLR4 is required for sterile inflammation establishment at the end of pregnancy and that it may be dysregulated in the pathological premature rupture of membranes.

cell biology↗

bioRxiv2018

Inhibition of the Receptor for Advanced Glycation End-Products in Acute Respiratory Distress Syndrome: A Randomised Laboratory Trial in Piglets

BackgroundThe receptor for advanced glycation end products (RAGE) modulates the pathogenesis of acute respiratory distress syndrome (ARDS). RAGE inhibition was recently associated with attenuated lung injury and restored alveolar fluid clearance (AFC) in a mouse model of ARDS. However, clinical translation will first require assessment of this strategy in larger animals.\n\nMethodsForty-eight anaesthetised Landrace piglets were randomised into a control group and three treatment groups. Animals allocated to treatment groups underwent orotracheal instillation of hydrochloric acid i) alone; ii) in combination with intravenous administration of a RAGE antagonist peptide (RAP), a S100P-derived peptide that prevents activation of RAGE by its ligands, or iii) in combination with intravenous administration of recombinant soluble (s)RAGE that acted as a decoy receptor. The primary outcome measure was net AFC at 4 h. Arterial oxygenation was assessed hourly for 4 h and alveolar-capillary permeability, alveolar inflammation, lung histology and lung mRNA expression of the epithelial sodium channel (1-ENaC), 1-Na,K-ATPase and aquaporin (AQP)-5 were assessed at 4 h.\n\nFindingsTreatment with either RAP or sRAGE improved net AFC rates (median [interquartile range], 21.2 [18.8-21.7] and 19.5 [17.1-21.5] %/h, respectively, versus 12.6 [3.2-18.8] %/h in injured, untreated controls), improved oxygenation and decreased alveolar inflammation and histological evidence of tissue injury after acid-induced ARDS. RAGE inhibition also restored lung mRNA expression of 1-Na,K-ATPase and AQP-5.\n\nInterpretationRAGE inhibition restored AFC and attenuated lung injury in a piglet model of acid-induced ARDS.\n\nFundingAuvergne Regional Council, Agence Nationale de la Recherche, Direction Generale de lOffre de Soins.\n\nResearch in ContextO_ST_ABSEvidence before this studyC_ST_ABSThe acute respiratory distress syndrome (ARDS), a clinical syndrome of diffuse pulmonary oedema and inflammation, currently lacks effective therapies and is associated with high mortality and morbidity. The degrees of lung epithelial injury and of alveolar fluid clearance (AFC) impairment, as evaluated by plasma levels of soluble receptor for glycation end-products (RAGE), are major prognostic factors in ARDS and potential therapeutic targets for ongoing research. For example, targeting RAGE with recombinant sRAGE or an anti-RAGE monoclonal antibody has proven beneficial in a translational mouse model of acid-induced ARDS.\n\nAdded value of this studyIn a piglet model of acid-induced ARDS, treatment with RAGE antagonist peptide or recombinant sRAGE restored AFC and attenuated the features of lung injury, thereby confirming, in the closest evolutionary model species to humans, previous evidence from rodent models that modulation of RAGE may be a therapeutic option for ARDS. Although this is an important step towards future clinical translation, future studies should assess the best methods to modulate RAGE and further confirm the safety of manipulating this pathway in patients with ARDS.

physiology↗