18 research outputs found
Modeling human endometrial decidualization from the interaction between proteome and secretome
CONTEXT: Decidualization of the human endometrium, which involves morphological and biochemical modifications of the endometrial stromal cells (ESCs), is a prerequisite for adequate trophoblast invasion and placenta formation. OBJECTIVE: This study aims to investigate the proteome and secretome of in vitro decidualized ESCs. These data were combined with published genomic information and integrated to model the human decidualization interactome. DESIGN: Prospective experimental case-control study. SETTING: A private research foundation. PATIENTS: Sixteen healthy volunteer ovum donors. INTERVENTION: Endometrial samples were obtained, and ESCs were isolated and decidualized in vitro. MAIN OUTCOME MEASURES: Two-dimensional difference in-gel electrophoresis, matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry, Western blot, human protein cytokine array, ELISA, and bioinformatics analysis were performed. RESULTS: The proteomic analysis revealed 60 differentially expressed proteins (36 over- and 24 underexpressed) in decidualized versus control ESCs, including known decidualization markers (cathepsin B) and new biomarkers (transglutaminase 2, peroxiredoxin 4, and the ACTB protein). In the secretomic analysis, a total of 13 secreted proteins (11 up- and 2 down-regulated) were identified, including well-recognized markers (IGF binding protein-1 and prolactin) and novel ones (myeloid progenitor inhibitory factor-1 and platelet endothelial cell adhesion molecule-1). These proteome/secretome profiles have been integrated into a decidualization interactome model. CONCLUSIONS: Proteomic and secretomic have been used as hypothesis-free approaches together with complex bioinformatics to model the human decidual interactome for the first time. We confirm previous knowledge, describe new molecules, and we have built up a model for human in vitro decidualization as invaluable tool for the diagnosis, therapy, and interpretation of biological phenomena.The participation of T.G.-G. was supported by a grant of the Ministry of Education and Science AP2007-04066 (FPU). CNIC was supported by the Spanish Ministry of Science and Innovation and the Pro-CNIC Foundation.S
Graphene and related materials in hierarchical fiber composites: Production techniques and key industrial benefits
Fiber-reinforced composites (FRC) are nowadays one of the most widely used class of high-tech materials. In particular, sporting goods, cars and the wings and fuselages of airplanes are made of carbon fiber reinforced composites (CFRC). CFRC are mature commercial products, but are still challenging materials. Their mechanical and electrical properties are very good along the fiber axis, but can be very poor perpendicular to it; interfacial interactions have to be tailored for specific applications to avoid crack propagation– and delamination; fiber production includes high-temperature treatments of adverse environmental impact, leading to high costs. Recent research work shows that the performance of CFRC can be improved by addition of graphene or related 2-dimensional materials (GRM). Graphene is a promising additive for CFRC because: 1) Its all-carbon aromatic structure is similar to the one of carbon fiber (CF). 2) Its 2-dimensional shape, high aspect ratio, high flexibility and mechanical strength allow it to be used as a coating on the surface of fiber, or as a mechanical/electrical connection between different fiber layers. 3) Its tunable surface chemistry allows its interaction to be enhanced with either the fiber or the polymer matrix used in the composite and 4) in contrast to carbon fibers or nanotubes, it is easily produced on a large scale at room temperature, without metal catalysts. Here, we summarize the key strategic advantages that could be obtained in this way, and some of the recent results that have been obtained in this field within the Graphene Flagship project and worldwide
Urinary metals and metal mixtures and oxidative stress biomarkers in an adult population from Spain: The Hortega Study
INTRODUCTION: Few studies have investigated the role of exposure to metals and metal mixtures on oxidative stress in the general population. OBJECTIVES: We evaluated the cross-sectional association of urinary metal and metal mixtures with urinary oxidative stress biomarkers, including oxidized to reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), and 8‑oxo‑7,8‑dihydroguanine (8-oxo-dG), in a representative sample of a general population from Spain (Hortega Study). METHODS: Urine antimony (Sb), barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), molybdenum (Mo), vanadium (V) and zinc (Zn) were measured by ICPMS in 1440 Hortega Study participants. RESULTS: The geometric mean ratios (GMRs) of GSSG/GSH comparing the 80th to the 20th percentiles of metal distributions were 1.15 (95% confidence intervals [95% CI]: 1.03-1.27) for Mo, 1.17 (1.05-1.31) for Ba, 1.23 (1.04-1.46) for Cr and 1.18 (1.00-1.40) for V. For MDA, the corresponding GMRs (95% CI) were 1.13 (1.03-1.24) for Zn and 1.12 (1.02-1.23) for Cd. In 8-oxo-dG models, the corresponding GMR (95% CI) were 1.12 (1.01-1.23) for Zn and 1.09 (0.99-1.20) for Cd. Cr for GSSG/GSH and Zn for MDA and 8-oxo-dG drove most of the observed associations. Principal component (PC) 1 (largely reflecting non-essential metals) was positively associated with GSSG/GSH. The association of PC2 (largely reflecting essential metals) was positive for GSSG/GSH but inverse for MDA. CONCLUSIONS: Urine Ba, Cd, Cr, Mo, V and Zn were positively associated with oxidative stress measures at metal exposure levels relevant for the general population. The potential health consequences of environmental, including nutritional, exposure to these metals warrants further investigation
Urinary metals and metal mixtures and oxidative stress biomarkers in an adult population from Spain: The Hortega Study.
Few studies have investigated the role of exposure to metals and metal mixtures on oxidative stress in the general population.
We evaluated the cross-sectional association of urinary metal and metal mixtures with urinary oxidative stress biomarkers, including oxidized to reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), and 8‑oxo‑7,8‑dihydroguanine (8-oxo-dG), in a representative sample of a general population from Spain (Hortega Study).
Urine antimony (Sb), barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), molybdenum (Mo), vanadium (V) and zinc (Zn) were measured by ICPMS in 1440 Hortega Study participants.
The geometric mean ratios (GMRs) of GSSG/GSH comparing the 80th to the 20th percentiles of metal distributions were 1.15 (95% confidence intervals [95% CI]: 1.03-1.27) for Mo, 1.17 (1.05-1.31) for Ba, 1.23 (1.04-1.46) for Cr and 1.18 (1.00-1.40) for V. For MDA, the corresponding GMRs (95% CI) were 1.13 (1.03-1.24) for Zn and 1.12 (1.02-1.23) for Cd. In 8-oxo-dG models, the corresponding GMR (95% CI) were 1.12 (1.01-1.23) for Zn and 1.09 (0.99-1.20) for Cd. Cr for GSSG/GSH and Zn for MDA and 8-oxo-dG drove most of the observed associations. Principal component (PC) 1 (largely reflecting non-essential metals) was positively associated with GSSG/GSH. The association of PC2 (largely reflecting essential metals) was positive for GSSG/GSH but inverse for MDA.
Urine Ba, Cd, Cr, Mo, V and Zn were positively associated with oxidative stress measures at metal exposure levels relevant for the general population. The potential health consequences of environmental, including nutritional, exposure to these metals warrants further investigation.This work was supported by the Strategic Action for Research in Health Sciences [CP12/03080, PI10/0082, PI13/01848, PI07/0497 and PI11/00726]; GRUPOS 03/101, PROMETEO/2009/029 and 2005/027, AMP07/075 and ACOMP/2013/039 from the Valencia Government; GRS/279/A/08 from Castilla-Leon Government; European Network of Excellence Ingenious Hypercare (EPSS-037093) from the European Commission; Retics (PREDIMED RD06/0045/0006); CIBER Fisiopatología Obesidad y Nutrición (CIBERobn) [CIBER-02-08-2009, CB06/03 and CB12/03/30016] and CIBER de Diabetes y Enfermedades Metabólicas Relacionadas (CIBERDEM CB07/0/018). The Strategic Action for Research in Health sciences, Retics, CIBEROBN and CIBERDEM are initiatives from Carlos III Health Institute Madrid and the Spanish Ministry of Economy and Competitiveness and co-funded with European Funds for Regional Development (FEDER). The authors declare they have no actual or potential competing financial interests.S
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Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology
In preeclampsia (PE), cytotrophoblast (CTB) invasion of the uterus and spiral arteries is often shallow. Thus, the placenta's role has been a focus. In this study, we tested the hypothesis that decidual defects are an important determinant of the placental phenotype. We isolated human endometrial stromal cells from nonpregnant donors with a previous pregnancy that was complicated by severe PE (sPE). Compared with control cells, they failed to decidualize in vitro as demonstrated by morphological criteria and the analysis of stage-specific antigens (i.e., IGFBP1, PRL). These results were bolstered by global transcriptional profiling data that showed they were transcriptionally inert. Additionally, we used laser microdissection to isolate the decidua from tissue sections of the maternal-fetal interface in sPE. Global transcriptional profiling revealed defects in gene expression. Also, decidual cells from patients with sPE, which dedifferentiated in vitro, failed to redecidualize in culture. Conditioned medium from these cells failed to support CTB invasion. To mimic aspects of the uterine environment in normal pregnancy, we added PRL and IGFBP1, which enhanced invasion. These data suggested that failed decidualization is an important contributor to down-regulated CTB invasion in sPE. Future studies will be aimed at determining whether this discovery has translational potential with regard to assessing a woman's risk of developing this pregnancy complication
Arsenic exposure and human blood DNA methylation and hydroxymethylation profiles in two diverse populations from Bangladesh and Spain
This work was supported by the Strategic Action for Research in Health sciences (PI15/00071) and CIBERCV, which are initiatives from Instituto de Salud Carlos III and the Spanish Ministry of Science and Innovation and co-funded with European Funds for Regional Development (FEDER) , and the United States National Institute of Health (grants R01 CA133595, P30 ES009089, T32 ES007322, P42 ES010349, and F31 ES029019) . MTP was supported by the Third AstraZeneca Award for Spanish Young Researchers. ADR received the support of a fellowship from "la Caixa" Foundation (ID 100010434, fellowship code "LCF/BQ/DR19/11740016") .Domingo-Relloso, A.; Bozack, A.; Kiihl, S.; Rodriguez-Hernandez, Z.; Rentero-Garrido, P.; Casasnovas, JA.; Leon-Latre, M.... (2022). Arsenic exposure and human blood DNA methylation and hydroxymethylation profiles in two diverse populations from Bangladesh and Spain. Environmental Research. 204:1-12. https://doi.org/10.1016/j.envres.2021.11202111220