Volatile anesthetics have demonstrated anti-inflammatory and epithelial-protective effects in several sterile experimental models of acute lung injury (ALI). However, their effects in endotoxin-induced ALI remain unclear, and recent clinical data have raised concerns regarding their potential impact on patient outcomes. We investigated whether sevoflurane restores alveolar fluid clearance (AFC) and preserves epithelial integrity in a murine model of lipopolysaccharide (LPS)-induced ALI. Wild-type (WT) and receptor for advanced glycation end-products-deficient (RAGE-/-) mice received intratracheal lipopolysaccharide (LPS) and were exposed to sevoflurane (1 vol %) or control gas for 1 h. Our primary outcome, the net AFC rate was measured 48 h after injury. Secondary outcomes included lung histology, bronchoalveolar lavage (BAL) protein and cytokine levels, and lung expression of epithelial sodium channel (ENaC), water transporter aquaporin-5 (AQP5), and adherens junction protein E-cadherin. LPS induced significant weight loss and severe lung injury, with impaired AFC and downregulation of ENaC and AQP5. Sevoflurane did not restore AFC, reduce alveolar-capillary permeability, or preserve epithelial junctional integrity. RAGE-/- mice exhibited attenuated lung injury and partial preservation of epithelial marker expression, without a statistically significant interaction with sevoflurane exposure. BAL cytokine levels were largely unaffected by sevoflurane. These findings suggest context-dependent effects of a 1-h exposure to 1.0 vol% sevoflurane in experimental ALI, with absence of epithelial benefit in a mouse model of endotoxin-induced ALI, in contrast with previously reported effects in a sterile model. This work may provide mechanistic insight into the differential translational impact of inhaled sedation strategies.

INTRODUCTION:The identification of early biomarkers is a critical prerequisite for the development and optimization of preventive strategies targeting preterm prelabour rupture of membranes (pPROM). The aim of this systematic review was to evaluate first trimester serum biomarkers for predicting the occurrence of pPROM. CONTENT:This is a systematic review of the literature made according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline. Articles were extracted from the Medline, Embase, and Web of Science databases using the keywords "first trimester" and "prelabour rupture of membranes". Two investigators used a systematic strategy to select eligible publications. SUMMARY:We selected 28 studies of interest representing 7,928 cases of pPROM. A significant association was found between pPROM and thirteen biomarkers. None of them predicted pPROM accurately when assessed by single-biomarker approaches. Results were pooled to evaluate PAPP-A, AGE, CX3CL1 and platelet count and volume, representing respectively 330, 91, 204 and 378 cases of pPROM. Other biomarkers had not been studied in enough trials for data to be combined. PAPP-A was the most widely studied biomarker, offering the best confidence and the largest effect (-0.84 [-1.33; -0.35]). The best sensitivity was found for CX3CL1, with a small to moderate effect size (0.34 [0.16-0.52]). Platelet volume exhibited a moderate effect size (-0.62 [-0.97; -0.26]). OUTLOOK:Our review highlights the urgent need for well-designed studies to identify biomarkers for early prediction of pPROM, including combined approaches.

The receptor for advanced glycation end products (RAGE) is a membrane protein involved in many diseases linked to epithelial dysfunction. Its activation mechanism remains unclear because RAGE lacks intrinsic kinase activity depending on other kinases for phosphorylation. Using an epithelial amniotic cell model (FL cells), researchers combined mass spectrometry, phosphorylation assays, microscale thermophoresis to show that RAGE intracellular domain binds to the α subunit of protein kinase CK2, leading to the phosphorylation of RAGE at serine 400. Ser400Ala mutation preserves CK2α binding but disrupts downstream signaling, altering phosphorylation of the transcription factors CREB (Ser133) and c-Jun (Ser63) after AGE ligands stimulation. In silico analyses identify binding sites for these two transcription factors in the connexin 43 promoter/UTR, a known RAGE target, associated with the overexpression of its mRNA. Overall, these findings highlight that phosphorylation at serine 400 is essential for RAGE signaling and transcriptional regulation in response to AGE ligands.

Phthalate esters (PAEs), which are widely used as plasticizers in various products, are recognized as endocrine-disrupting chemicals (EDCs) that can affect female reproductive health. Numerous studies linked PAE exposure to several health hazards, including disruption of folliculogenesis, steroidogenesis, implantation, and pregnancy maintenance, contributing to complications such as miscarriage, preeclampsia, and preterm birth. In response to growing concerns regarding their toxicity, alternative plasticizers (APs) have been introduced, with particular attention given to the commonly used compounds, including di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH), tris(2-ethylhexyl) trimellitate (TOTM), di(2-ethylhexyl) adipate (DEHA), and acetyl tributyl citrate (ATBC). While these alternatives are often presented as safer, recent studies have suggested that these compounds can also disrupt hormonal pathways and fertility regulation mechanisms. Both PAEs and APs have been shown to interact with key nuclear receptor systems, especially with peroxisome proliferator-activated receptors (PPARs) and steroid hormone receptors. These receptors are essential regulators of ovarian function, placental development, and pregnancy maintenance. Disruption of these signaling pathways, particularly in the placenta and fetal membranes, may contribute to altered inflammatory responses, impaired endocrine regulation, and increased risk of adverse pregnancy outcomes. This review provides a state-of-the-art synthesis of the current literature on PAEs and APs, focusing on exposure patterns, associations with female reproductive health and pregnancy outcomes, and the identification of dysregulated biological pathways. This review emphasizes the urgent need to limit plasticizer exposure, especially among women of reproductive age, in order to preserve reproductive health and prevent associated complications.

OBJECTIVE:To describe the temporal trends in Preterm prelabour rupture of membranes (PPROM) in metropolitan France and the geographical distribution at the administrative division level. DESIGN:Exploratory population-based study using administrative data of the French National Health Data System. SETTING:Metropolitan France, 2015 to 2023. POPULATION:Pregnancy with a diagnosis of PROM before 37 SA. METHODS:Annual crude incidence of PPROM was calculated by dividing the number of pregnancies with PPROM diagnosis by the number of live births recorded during the same period. Annual trend was estimated by a binomial negative mixed model. Smoothed standardised incidence ratios were estimated based on a BYM2 model, which accounts for spatial variability between departments. MAIN OUTCOME:PPROM cases, defined as pregnancies with first hospitalizations with a diagnosis of PROM before 37 weeks. RESULTS:Over the study period, we included 150 615 PPROM cases representing 16 735 (±596) per year. Incidence of PPROM cases showed an ascending trend over time (incidence rate ratio 1.023 per year; 95% CI: 1.017-1.030) with an annual crude incidence ranging from 2.2% in 2015 to 2.7% in 2023. A decrease in the incidence was observed in 2020 relative to other years (incidence rate ratio 0.903, 95% CI: 0.887-0.920). A map of smoothed SIRs of PPROM cases at the French administrative division level revealed geographical inequalities. CONCLUSIONS:This first population-based study describing PPROM cases in metropolitan France paves the way for further studies to explore environmental hypotheses. Identifying temporal and geographical disparities in PPROM incidence is relevant to public health policy and practice as such disparities argue for the development of targeted prevention strategies in high-risk areas.

Spontaneous preterm birth (SPTB) includes two distinct presentations: preterm labor with intact membranes (PTL-IM) and preterm premature rupture of membranes (PPROM), both associated with inflammation. In prior work, we identified first-trimester serum CX3CL1, a membrane-bound chemokine cleaved by the metalloprotease ADAM10, as an independent predictive blood biomarker for PPROM. The present study aimed to characterize the expression of ADAM10 and CX3CL1 in fetal membranes and maternal serum across gestation, and to assess serum ADAM10 as a potential predictive biomarker for SPTB. mRNA and protein expression of CX3CL1 and ADAM10 was assessed in 26 fetal membranes (amnion and choriodecidua). Serum ADAM10 was measured in a prospective cohort of 438 pregnant women with samples collected in the first trimester, second trimester and delivery. CX3CL1 expression increased in the choriodecidua during the second trimester and declined at term. ADAM10 mRNA remained stable in the amnion, while protein levels peaked in the choriodecidua in the second trimester and at term. Serum ADAM10 showed a similar pattern, with significantly higher levels in second-trimester PTL-IM cases versus term deliveries. Second trimester serum ADAM10 significantly enhanced the predictive ability of maternal risk factors for PTL-IM. Area under the ROC curve was 0.73 (95 % confidence interval: 0.65-0.81). This model identified cases with a 72 % (59 %-82 %) sensitivity and a 64 % (55 %-72 %) specificity. ADAM10 and CX3CL1 are expressed in the fetal-maternal interface, and their soluble forms measured in blood may help in the early identification of SPTB.

Exposure to ambient particulate matter (PM) with an aerodynamic diameter of <10 μm (PM10) is a well-established health hazard. There is increasing evidence that geogenic (Earth-derived) particles can induce adverse biological effects upon inhalation, though there is high variability in particle bioreactivity that is associated with particle source and physicochemical properties. In this study, we investigated physicochemical properties and biological reactivity of volcanic ash from the April 2021 eruption of La Soufrière volcano, St. Vincent, and two desert dust samples: a standardized test dust from Arizona and an aeolian Gobi Desert dust sampled in China. We determined particle size, morphology, mineralogy, surface texture and chemistry in sub-10 μm material to investigate associations between particle physicochemical properties and observed bioreactivity. We assessed cellular responses (cytotoxic and pro-inflammatory effects) to acute particle exposures (24 hr) in monocultures at the air-liquid interface using two types of cells of the human airways: BEAS-2B bronchial epithelial cells and A549 alveolar type II epithelial cells. In acellular assays, we also assessed particle oxidative potential and the presence of microorganisms. The results showed that volcanic ash and desert dust exhibit intrinsically different particle morphology, surface textures and chemistry, and variable mineralogical content. We found that Gobi Desert dust is more bioreactive than freshly erupted volcanic ash and Arizona test dust, which is possibly linked to the presence of microorganisms (bacteria) and/or nanoscale elongated silicate minerals (potentially clay such as illite or vermiculite) on particle surfaces.

Plasticizers, particularly phthalates, are widely used to enhance the properties of plastics, yet their harmful effects on human health, especially reproductive health, have raised concerns. This has led governments to promote the use of non-phthalate substitutes. Preterm premature rupture of fetal membranes (PPROM), affecting 3-4% of pregnancies and contributing to 40-50% of preterm births worldwide, has been associated with traditional phthalate exposure. However, no clear link has yet been established between alternative plasticizers and preterm births. Among these substitutes, DINCH (used as a phthalate replacement) and its metabolite, MINCH, appear to be promising options, although their health impacts remain largely unexplored. This study aims to assess the potential effects of DINCH and MINCH on the physiology of fetal membranes, focusing on the nuclear receptor PPARγ, which plays a critical role in pregnancy maintenance. An amniotic epithelial cell model was used to evaluate DINCH and MINCH influence on cytotoxicity, cell viability, and PPARγ activity, including its anti-inflammatory properties. Both exhibited no cytotoxic effects, did not alter PPARγ expression, and did not affect its anti-inflammatory properties. These findings suggest that DINCH and MINCH could serve as safe alternatives to phthalates, potentially reducing the risk of weakening and premature rupture of fetal membranes.

Despite being one of the largest intrauterine tissues in surface area, the fetal membrane that lines the intrauterine cavity is often overlooked, forgotten, or misidentified in clinical and basic science research. The feto-maternal interface is comprised of the fetal membrane (fetal component) and decidua parietalis (maternal component), which lines the intrauterine cavity and provides essential mechanical, immune, hormonal, and transport support to maintain pregnancy. Fetal membrane plays an important role in triggering and regulating labor via complex signaling cascades. Whilst several researchers have investigated the membranes world-wide, nomenclature remains inconsistent, leading to widespread ambiguity across inter-disciplinary disciplines involving science, bioengineering, and reproductive medicine. The ongoing confusion regarding its terminology, origins, structure, and function has resulted in several significant issues, including diagnostic errors and misrepresentation clinically, limitations and inaccuracies in scientific research, and regulatory and clinical miscommunication. Therefore, the Fetal Membrane Society (FMS) calls upon the field to standardize fetal membrane nomenclature, define its architecture, and summarize its region-specific differences to facilitate understanding of its biological role. Clear and consistent identification of the fetal membrane is essential in improving research accuracy, clinical outcomes, and effective communication within and between the medical and scientific communities.

Objectives The objective of our study was to evaluate serum CX3CL1/Fractalkine, a monocyte/macrophage chemoattractant expressed in cytotrophoblasts and decidual cells, as a predictive biomarker for the occurrence of preterm premature rupture of membranes (PPROM). Methods A case-control study of 438 pregnancies including 82 PPROM cases and 64 preterm labor with intact membranes cases with blood samples collected at first trimester, second trimester and delivery was conducted. The predictive ability of CX3CL1 and maternal risk factors for the occurrence of PPROM was assessed by receiver operating characteristic curve analysis. A second, independent cohort was prospectively constituted to confirm the case-control study results. Results First trimester CX3CL1 was significantly increased in PPROM cases when compared to matched controls. Multivariate regression analysis highlighted a significant difference for CX3CL1 measured during the first trimester (p<0.001). Alone, CX3CL1 predicts PPROM with a 90 % sensitivity and a specificity around 40 %. The area under the receiver operating characteristic curve for PPROM prediction were 0.64 (95% confidence interval: 0.57-0.71) for first trimester CX3CL1, and 0.61 (95% confidence interval: 0.54-0.68) for maternal risk factors (body mass index<18.5 kg/m(2), nulliparity, tobacco use and the absence of high school diploma). The combination of CX3CL1 and maternal risk factors significantly improved the area under the curve: 0.72 (95% confidence interval: 0.66-0.79) (p<0.001). The results were confirmed on a second independent cohort. Conclusions CX3CL1 is a promising blood biomarker in the early (first trimester) prediction of PPROM.

The human fetal membrane is a globally accepted biological biomaterial for wound and tissue repair and regeneration in numerous fields, including dermatology, ophthalmology, and more recently orthopedics, maxillofacial and oral surgery, and nerve regeneration. Both cells and matrix components of amnion and chorion are beneficial, releasing a diverse range of growth factors, cytokines, peptides, and soluble extracellular matrix components. Beside fetal membranes, numerous natural materials have also been reported to promote wound healing. The biological properties of these materials may potentiate the pro-healing action of fetal membranes. Comparison of such materials with fetal membranes has been scant, and their combined use with fetal membranes has been underexplored. This review presents an up-to-date overview of (i) clinical applications of human fetal membranes in wound healing and tissue regeneration; (ii) studies comparing human fetal membranes with natural materials for promoting wound healing; and (iii) the literature on the combined use of fetal membranes and natural pro-healing materials.

Acute respiratory distress syndrome (ARDS) is a serious lung condition that often leads to hospitalization in intensive care units and a high mortality rate. Sevoflurane is a volatile anesthetic with growing interest for sedation in ventilated patients with ARDS. It has been shown to have potential lung -protective effects, such as reduced inflammation and lung edema, or improved arterial oxygenation. In this study, we investigated the effects of sevoflurane on lung injury in cultured human carcinoma -derived lung alveolar epithelial (A549) cells. We found that sevoflurane was associated with improved wound healing after exposure to inflammatory cytokines, with preserved cell proliferation but no effect on cell migration properties. Sevoflurane exposure was also associated with enhanced cell viability and active autophagy in A549 cells exposed to cytokines. These findings suggest that sevoflurane may have beneficial effects on lung epithelial injury by promoting alveolar epithelial wound healing and by influencing the survival and proliferation of A549 epithelial cells in vitro . Further research is needed to confirm these findings and to investigate the key cellular mechanisms explaining sevoflurane 's potential effects on lung epithelial injury.

In recent decades, preterm birth (PTB) has become a significant research focus in the healthcare field, as it is a leading cause of neonatal mortality worldwide. Using five independent study cohorts including 1290 vaginal samples from 561 pregnant women who delivered at term ( n = 1029) or prematurely ( n = 261), we analysed vaginal metagenomics data for precise microbiome structure characterization. Then, a deep neural network (DNN) was trained to predict term birth (TB) and PTB with an accuracy of 84.10% and an area under the receiver operating characteristic curve (AUROC) of 0.875 ± 0.11. During a benchmarking process, we demonstrated that our DL model outperformed seven currently used machine learning algorithms. Finally, our results indicate that overall diversity of the vaginal microbiota should be taken in account to predict PTB and not specific species. This artificial-intelligence based strategy should be highly helpful for clinicians in predicting preterm birth risk, allowing personalized assistance to address various health issues. DeepMPTB is open source and free for academic use. It is licensed under a GNU Affero General Public License 3.0 and is available at https://deepmptb.streamlit.app/ . Source code is available at https://github.com/oschakoory/DeepMPTB and can be easily installed using Docker ( https://www.docker.com/ ).

At the feto-maternal interface, fetal membranes (FM) play a crucial role throughout pregnancy. FM rupture at term implicates different sterile inflammation mechanisms including pathways activated by the transmembrane glycoprotein receptor for advanced glycation end-products (RAGE) belonging to the immunoglobulin superfamily. As the protein kinase CK2 is also implicated in the inflammation process, we aimed to characterize the expressions of RAGE and the protein kinase CK2 as a candidate regulator of RAGE expression. The amnion and choriodecidua were collected from FM explants and/or primary amniotic epithelial cells throughout pregnancy and at term in spontaneous labor (TIL) or term without labor (TNL). The mRNA and protein expressions of RAGE and the CK2α, CK2α′, and CK2β subunits were investigated using reverse transcription quantitative polymerase chain reaction and Western blot assays. Their cellular localizations were determined with microscopic analyses, and the CK2 activity level was measured. RAGE and the CK2α, CK2α′, and CK2β subunits were expressed in both FM layers throughout pregnancy. At term, RAGE was overexpressed in the amnion from the TNL samples, whereas the CK2 subunits were expressed at the same level in the different groups (amnion/choriodecidua/amniocytes, TIL/TNL), without modification of the CK2 activity level and immunolocalization. This work paves the way for future experiments regarding the regulation of RAGE expression by CK2 phosphorylation.

Exposure to volatile organic compounds (VOCs) during the fetal period may induce negative effects on children’s health (e.g. increased risk of low birth weight and imbalanced development). Whereas VOCs have been analysed extensively in various human biological fluids (i.e. urine, blood, and breath), during pregnancy only urine has been studied and no work has been performed on amniotic fluid (AF), which is in direct contact with the fetus and is essential for its well-balanced development and maturation. This study aimed to detect VOCs in AF and to investigate their links to the lifestyle habits of pregnant women. The VOC composition of the AF collected from 76 healthy pregnant women was analysed using a gas chromatograph coupled to a mass spectrometer. The sources of VOC exposure in pregnant women were assessed using a questionnaire about their home living conditions and their professional exposure. A total of 126 VOCs belonging to 13 chemical families were detected in AF. The majority of these VOCs (92) had an exogenous origin, and their presence was linked to lifestyle habits, especially smoking and fragrance use. Considering the direct contact of these VOCs with multiple fetal organs, this study is an important contribution to the literature exploring the future potential relationships between VOCs and abnormal fetal development.

Dry eye inflammation is a key step in a vicious circle and needs to be better understood in order to break it. The goals of this work were to, first, characterize alarmins and cytokines released by ocular surface cells in the hyperosmolar context and, second, study the role of NFAT5 in this process. Finally, we studied the potential action of these alarmins in ocular surface epithelial cells and macrophages via RAGE pathways. HCE and WKD cell lines were cultured in a NaCl-hyperosmolar medium and the expression of alarmins (S100A4, S100A8, S100A9, and HMGB1), cytokines (IL6, IL8, TNFα, and MCP1), and NFAT5 were assessed using RT-qPCR, ELISA and multiplex, Western blot, immunofluorescence, and luciferase assays. In selected experiments, an inhibitor of RAGE (RAP) or NFAT5 siRNAs were added before the hyperosmolar stimulations. HCE and WKD cells or macrophages were treated with recombinant proteins of alarmins (with or without RAP) and analyzed for cytokine expression and chemotaxis, respectively. Hyperosmolarity induced epithelial cell inflammation depending on cell type. NFAT5, but not RAGE or alarmins, participated in triggering epithelial inflammation. Furthermore, the release of alarmins induced macrophage migration through RAGE. These in vitro results suggest that NFAT5 and RAGE have a role in dry eye inflammation.

Background Preclinical studies in acute respiratory distress syndrome (ARDS) have suggested that inhaled sevoflurane may have lung-protective effects and clinical trials are ongoing to assess its impact on major clinical outcomes in patients with ARDS. However, the underlying mechanisms of these potential benefits are largely unknown. This investigation focused on the effects of sevoflurane on lung permeability changes after sterile injury and the possible associated mechanisms. Methods To investigate whether sevoflurane could decrease lung alveolar epithelial permeability through the Ras homolog family member A (RhoA)/phospho-Myosin Light Chain 2 (Ser19) (pMLC)/filamentous (F)-actin pathway and whether the receptor for advanced glycation end-products (RAGE) may mediate these effects. Lung permeability was assessed in RAGE −/− and littermate wild-type C57BL/6JRj mice on days 0, 1, 2, and 4 after acid injury, alone or followed by exposure at 1% sevoflurane. Cell permeability of mouse lung epithelial cells was assessed after treatment with cytomix (a mixture of TNFɑ, IL-1β, and IFNγ) and/or RAGE antagonist peptide (RAP), alone or followed by exposure at 1% sevoflurane. Levels of zonula occludens-1, E-cadherin, and pMLC were quantified, along with F-actin immunostaining, in both models. RhoA activity was assessed in vitro. Results In mice after acid injury, sevoflurane was associated with better arterial oxygenation, decreased alveolar inflammation and histological damage, and non-significantly attenuated the increase in lung permeability. Preserved protein expression of zonula occludens-1 and less increase of pMLC and actin cytoskeletal rearrangement were observed in injured mice treated with sevoflurane. In vitro, sevoflurane markedly decreased electrical resistance and cytokine release of MLE-12 cells, which was associated with higher protein expression of zonula occludens-1. Improved oxygenation levels and attenuated increase in lung permeability and inflammatory response were observed in RAGE −/− mice compared to wild-type mice, but RAGE deletion did not influence the effects of sevoflurane on permeability indices after injury. However, the beneficial effect of sevoflurane previously observed in wild-type mice on day 1 after injury in terms of higher PaO 2 /FiO 2 and decreased alveolar levels of cytokines was not found in RAGE −/− mice. In vitro, RAP alleviated some of the beneficial effects of sevoflurane on electrical resistance and cytoskeletal rearrangement, which was associated with decreased cytomix-induced RhoA activity. Conclusions Sevoflurane decreased injury and restored epithelial barrier function in two in vivo and in vitro models of sterile lung injury, which was associated with increased expression of junction proteins and decreased actin cytoskeletal rearrangement. In vitro findings suggest that sevoflurane may decrease lung epithelial permeability through the RhoA/pMLC/F-actin pathway. Graphical Abstract