Simple and Fast Prediction of Gestational Diabetes Mellitus Based on Machine Learning and Near-Infrared Spectra of Serum: A Proof of Concept Study at Different Stages of Pregnancy.

Gestational diabetes mellitus (GDM) is a hyperglycemic state that is typically diagnosed by an oral glucose tolerance test (OGTT), which is unpleasant, time-consuming, has low reproducibility, and results are tardy. The machine learning (ML) predictive models that have been proposed to improve GDM diagnosis are usually based on instrumental methods that take hours to produce a result. Near-infrared (NIR) spectroscopy is a simple, fast, and low-cost analytical technique that has never been assessed for the prediction of GDM. This study aims to develop ML predictive models for GDM based on NIR spectroscopy, and to evaluate their potential as early detection or alternative screening tools according to their predictive power and duration of analysis. Serum samples from the first trimester (before GDM diagnosis) and the second trimester (at the time of GDM diagnosis) of pregnancy were analyzed by NIR spectroscopy. Four spectral ranges were considered, and 80 mathematical pretreatments were tested for each. NIR data-based models were built with single- and multi-block ML techniques. Every model was subjected to double cross-validation. The best models for first and second trimester achieved areas under the receiver operating characteristic curve of 0.5768 ± 0.0635 and 0.8836 ± 0.0259, respectively. This is the first study reporting NIR-spectroscopy-based methods for the prediction of GDM. The developed methods allow for prediction of GDM from 10 µL of serum in only 32 min. They are simple, fast, and have a great potential for application in clinical practice, especially as alternative screening tools to the OGTT for GDM diagnosis.

Enhancing Alginate Hydrogels as Possible Wound-Healing Patches: The Synergistic Impact of Reduced Graphene Oxide and Tannins on Mechanical and Adhesive Properties.

Hydrogels are three-dimensional crosslinked materials known for their ability to absorb water, exhibit high flexibility, their biodegradability and biocompatibility, and their ability to mimic properties of different tissues in the body. However, their application is limited by inherent deficiencies in their mechanical properties. To address this issue, reduced graphene oxide (rGO) and tannins (TA) were incorporated into alginate hydrogels (Alg) to evaluate the impact of the concentration of these nanomaterials on mechanical and adhesive, as well as cytotoxicity and wound-healing properties. Tensile mechanical tests demonstrated improvements in tensile strength, elastic modulus, and toughness upon the incorporation of rGO and TA. Additionally, the inclusion of these materials allowed for a greater energy dissipation during continuous charge-discharge cycles. However, the samples did not exhibit self-recovery under environmental conditions. Adhesion was evaluated on pig skin, revealing that higher concentrations of rGO led to enhanced adhesion, while the concentration of TA did not significantly affect this property. Moreover, adhesion remained consistent after 10 adhesion cycles, and the contact time before the separation between the material and the surface did not affect this property. The materials were not cytotoxic and promoted healing in human fibroblast-model cells. Thus, an Alg/rGO/TA hydrogel with enhanced mechanical, adhesive, and wound-healing properties was successfully developed.

Multifunctional Chitosan Scaffold Platforms Loaded with Natural Polyphenolic Extracts for Wound Dressing Applications.

Chitosan (CS)-based scaffolds loaded with Pinus radiata extract bark (PE) and grape seed extract (GSE) were successfully developed for wound dressing applications. The effects of incorporating GSE and PE in CS scaffolds were investigated in relation to their physicochemical and biological properties. All scaffolds exhibited porous structures with the ability to absorb more than 70 times their weight when contacted with blood and phosphate buffer solution. The incorporation of GSE and PE into the CS scaffolds increased their blood absorption ability and degradation rates over time. All scaffolds showed a clotting ability above 95%, with their surfaces being favorable for red blood cell attachment. Both GSE and PE were released from the CS scaffolds in a sustained manner. Scaffolds loaded with GSE and PE inhibited the bacterial activity of S. aureus and E. coli by 40% and 44% after 24 h testing. In vitro cell viability studies demonstrated that all scaffolds were nontoxic to HaCaT cells. Importantly, the addition of GSE and PE further increased cell viability compared to that of the CS scaffold. This study provides a new synthesis method to immobilize GSE and PE on CS scaffolds, enabling the formation of novel material platforms with a high potential for wound dressing applications.

Metabolomics profiling and chemoresistance mechanisms in ovarian cancer cell lines: Implications for targeting glutathione pathway.

Ovarian cancer presents a significant challenge due to its high rate of chemoresistance, which complicates the effectiveness of drug-response therapy. This study provides a comprehensive metabolomic analysis of ovarian cancer cell lines OVCAR-3 and SK-OV-3, characterizing their distinct metabolic landscapes. Metabolomics coupled with chemometric analysis enabled us to discriminate between the metabolic profiles of these two cell lines. The OVCAR-3 cells, which are sensitive to doxorubicin (DOX), exhibited a preference for biosynthetic pathways associated with cell proliferation. Conversely, DOX-resistant SK-OV-3 cells favored fatty acid oxidation for energy maintenance. Notably, a marked difference in glutathione (GSH) metabolism was observed between these cell lines. Our investigations further revealed that GSH depletion led to a profound change in drug sensitivity, inducing a shift from a cytostatic to a cytotoxic response. The results derived from this comprehensive metabolomic analysis offer potential targets for novel therapeutic strategies to overcome drug resistance. Our study suggests that targeting the GSH pathway could potentially enhance chemotherapy's efficacy in treating ovarian cancer.

Ethical enactivism for smart and inclusive STEAM learning design.

Current global challenges of the 21st century promote STEAM (science, technology, engineering, arts and mathematics) education and digitalization as a means for humans to be the central actors in the construction of a sustainable society that favors a sense of worth and global wellbeing. In this scenario, new educational technology tools and immersive learning affordances (possibilities), offer unprecedented potential for the design of smart and dynamic learning systems and contexts that can enhance learning processes across varied audiences and educational settings. However, current STEAM education practice lacks attention to equipping all citizens with the necessary skills to use digital technologies in an ethical, critical and creative way. This gap calls for attention in design processes, principles and practices that are attentive to ethical considerations and values-based approaches. On the other hand, in its formulation STEAM as an educational approach is framed in four fundamental pillars: creativity, inclusion, citizenship and emerging technologies, which also put attention on the inclusion of disadvantaged and underrepresented social groups during STEAM education design. Following an apparent need to explore ethical and inclusive design in STEAM education, and inspired in the 4E cognition framework, ethical enactivism and embodied and ecosomaesthetics experience design, here we propose a theoretical framework grounded on systems thinking for the design of smart and dynamic STEAM learning systems and settings. The framework is aimed at STEAM educational psychologists, educational technologists, learning designers and educational practitioners who wish to address the global challenges of 21st century education by means of creative, innovative and inclusive education design.

Mutations in the bZip region of the CEBPA gene: A novel prognostic factor in patients with acute myeloid leukemia.

BACKGROUND: Hematopoiesis, the process of blood cell formation involves on a complex network of transcription factors. Among them, the CCAAT-enhancer-binding protein alpha (CEBPA) plays a crucial role in maintaining the balance between myeloid proliferation and differentiation. Imbalances in this network can lead to disrupted differentiation and contribute to the development of malignant diseases. AIM: Understanding of disease development and explore potential therapeutic strategies for hematological disorders associated CEPBA gen. MATERIALS AND METHODS: The research involved a comprehensive analysis of CEBPA gene mutations in the context of acute myeloid leukemia (AML). This encompassed a thorough exploration of point mutations and double mutations in AML patients. RESULTS: In the context of acute myeloid leukemia (AML), mutations in the CEBPA gene, especially point mutations, are frequently observed. A significant number of AML patients present with double mutations in CEBPA, which have been linked to a more favorable prognosis in terms of overall survival and event-free survival. These patients also tend to exhibit enhanced responsiveness to treatment. DISCUSSION: Unraveling the intricate interplay of transcription factors, particularly CEBPA, holds significant implications for decoding the mechanisms governing hematopoiesis. This understanding offers a potential avenue for deciphering disease development and devising novel therapeutic strategies for hematological disorders. CONCLUSION: The findings underscore that CEBPA mutations correlate with enhanced overall survival and event-free survival, with relevance to those presenting within the bZip framework. This knowledge may contribute to advancing personalized treatments for hematological conditions.

Machine learning applied in maternal and fetal health: a narrative review focused on pregnancy diseases and complications.

Introduction: Machine learning (ML) corresponds to a wide variety of methods that use mathematics, statistics and computational science to learn from multiple variables simultaneously. By means of pattern recognition, ML methods are able to find hidden correlations and accomplish accurate predictions regarding different conditions. ML has been successfully used to solve varied problems in different areas of science, such as psychology, economics, biology and chemistry. Therefore, we wondered how far it has penetrated into the field of obstetrics and gynecology. Aim: To describe the state of art regarding the use of ML in the context of pregnancy diseases and complications. Methodology: Publications were searched in PubMed, Web of Science and Google Scholar. Seven subjects of interest were considered: gestational diabetes mellitus, preeclampsia, perinatal death, spontaneous abortion, preterm birth, cesarean section, and fetal malformations. Current state: ML has been widely applied in all the included subjects. Its uses are varied, the most common being the prediction of perinatal disorders. Other ML applications include (but are not restricted to) biomarker discovery, risk estimation, correlation assessment, pharmacological treatment prediction, drug screening, data acquisition and data extraction. Most of the reviewed articles were published in the last five years. The most employed ML methods in the field are non-linear. Except for logistic regression, linear methods are rarely used. Future challenges: To improve data recording, storage and update in medical and research settings from different realities. To develop more accurate and understandable ML models using data from cutting-edge instruments. To carry out validation and impact analysis studies of currently existing high-accuracy ML models. Conclusion: The use of ML in pregnancy diseases and complications is quite recent, and has increased over the last few years. The applications are varied and point not only to the diagnosis, but also to the management, treatment, and pathophysiological understanding of perinatal alterations. Facing the challenges that come with working with different types of data, the handling of increasingly large amounts of information, the development of emerging technologies, and the need of translational studies, it is expected that the use of ML continue growing in the field of obstetrics and gynecology.

Self-Assembled CNF/rGO/Tannin Composite: Study of the Physicochemical and Wound Healing Properties.

In this study, a conductive composite material, based on graphene oxide (GO), nanocellulose (CNF), and tannins (TA) from pine bark, reduced using polydopamine (PDA), was developed for wound dressing. The amount of CNF and TA was varied in the composite material, and a complete characterization including SEM, FTIR, XRD, XPS, and TGA was performed. Additionally, the conductivity, mechanical properties, cytotoxicity, and in vitro wound healing of the materials were evaluated. A successful physical interaction between CNF, TA, and GO was achieved. Increasing CNF amount in the composite reduced the thermal properties, surface charge, and conductivity, but its strength, cytotoxicity, and wound healing performance were improved. The TA incorporation slightly reduced the cell viability and migration, which may be associated with the doses used and the extract's chemical composition. However, the in-vitro-obtained results demonstrated that these composite materials can be suitable for wound healing.

Body Adiposity Partially Mediates the Association between FTO rs9939609 and Lower Adiponectin Levels in Chilean Children.

Children carrying the minor allele 'A' at the fat mass and obesity-associated protein (FTO) gene have higher obesity prevalence. We examined the link between FTO rs9939609 polymorphism and plasma adiponectin and the mediating role of body adiposity, in a cross-sectional study comprising 323 children aged 6-11 years. Adiponectin and FTO genotypes were assessed using a commercial kit and a real-time polymerase chain reaction with high-resolution melting analysis, respectively. Body adiposity included body mass index z-score, body fat percentage and waist-to-hip ratio. To investigate adiponectin (outcome) associations with FTO and adiposity, linear regressions were implemented in additive models and across genotype categories, adjusting for sex, age and Tanner's stage. Using mediation analysis, we determined the proportion of the association adiponectin-FTO mediated by body adiposity. Lower adiponectin concentrations were associated with one additional risk allele (ßadditive = -0.075 log-µg/mL [-0.124; -0.025]), a homozygous risk genotype (ßAA/TT = -0.150 [-0.253; -0.048]) and a higher body mass index z-score (ß = -0.130 [-0.176; -0.085]). Similar results were obtained for body fat percentage and waist-to-hip ratio. Body adiposity may mediate up to 29.8% of the FTO-adiponectin association. In conclusion, FTO rs9939609-related differences in body adiposity may partially explain lower adiponectin concentrations. Further studies need to disentangle the biological pathways independent from body adiposity.

Adenosine promoted angiogenesis mediated by the release of small extracellular vesicles from human endothelial progenitor cells.

Endothelial progenitor cells (EPCs) are stem cells mainly derived from bone marrow; from where they migrate to repair and regenerate damaged tissues. eEPCs have been classified into two sub-populations, early (eEPC) and late EPCs (lEPC), depending on maturation stages in vitro. In addition, eEPC release endocrine mediators, including small extracellular vesicles (sEVs), which in turn may enhance the eEPC-mediated wound healing properties. Nevertheless, adenosine contributes to angiogenesis by recruiting eEPC at the injury site. However, whether ARs may enhance the secretome of eEPC, including sEVs, is unknown. Therefore, we aimed to investigate whether AR activation increase the release of sEVs in eEPC, which in turn has paracrine effects on recipient endothelial cells. Results shown that 5'-N-ethylcarboxamidoadenosine (NECA), a non-selective agonist, increase both the protein levels of the vascular endothelial growth factor (VEGF), and the number of sEVs released to the conditioned medium (CM) in primary culture of eEPC. Importantly, CM and EVs harvested from NECA-stimulated eEPC promote in vitro angiogenesis, without changes in cell proliferation, in recipient ECV-304 endothelial cells. This constitutes the first evidence showing that adenosine enhances sEVs release from eEPC, which has pro-angiogenic capacity on recipient endothelial cells.

Comparison of Diagnostic Models to Estimate the Risk of Metabolic Syndrome in a Chilean Pediatric Population: A Cross-Sectional Study.

The pediatric population has various criteria for measuring metabolic syndrome (MetS). The diversity of consensus for diagnosis has led to different non-comparable reported prevalence. Given the increase in its prevalence in pediatric ages, it is necessary to develop efficient methods to encourage early detection. Consequently, early screening for the risk of MetS could favor timely action in preventing associated comorbidities in adulthood. This study aimed to establish the diagnostic capacity of models that use non-invasive (anthropometric) and invasive (serum biomarkers) variables for the early detection of MetS in Chilean children. A cross-sectional study was carried out on 220 children aged 6 to 11. Multivariate logistic regressions and discriminant analyses were applied to determine the diagnostic capacity of invasive and non-invasive variables. Based on these results, four diagnostic models were created and compared: (i) anthropometric, (ii) hormonal (insulin, leptin, and adiponectin), (iii) Lipid A (high-density cholesterol lipoprotein [HDL-c] and triglycerides [TG]) and (iv) Lipid B (TG/HDL-c). The prevalence of MetS was 26.8%. Lipid biomarkers (HDL-c and TG) and their ratio (TG/HDL-c) presented higher diagnostic capacity, above 80%, followed by body mass index (BMI, 0.71-0.88) and waist-to-height ratio (WHtR, 0.70-0.87). The lipid model A was the most accurate (sensitivity [S] = 62.7%, specificity [E] = 96.9%, validity index 87.7%), followed by the anthropometric model (S = 69.5%, E = 88.8% and validity index = 83.6%). In conclusion, detecting MetS was possible through invasive and non-invasive methods tested in overweight and obese children. The proposed models based on anthropometric variables, or serum biomarkers of the lipid model A, presented acceptable validity indices. Moreover, they were higher than those that measured adipokines, leptin, and adiponectin. The anthropometric model was the most cost-effective and easy to apply in different environments.

The Effect on Hemostasis of Gelatin-Graphene Oxide Aerogels Loaded with Grape Skin Proanthocyanidins: In Vitro and In Vivo Evaluation.

Using in vitro and in vivo models, this study investigated the hemostatic potential to control bleeding of both unloaded gelatin-graphene oxide aerogels and the same loaded with proanthocyanidins (PAs) from Vitis vinifera grape skin extract. Our results showed that the physicochemical and mechanical properties of the aerogels were not affected by PA inclusion. In vitro studies showed that PA-loaded aerogels increased the surface charge, blood absorption capacity and cell viability compared to unloaded ones. These results are relevant for hemostasis, since a greater accumulation of blood cells on the aerogel surface favors aerogel-blood cell interactions. Although PAs alone were not able to promote hemostasis through extrinsic and intrinsic pathways, their incorporation into aerogels did not affect the in vitro hemostatic activity of these composites. In vivo studies demonstrated that both aerogels had significantly increased hemostatic performance compared to SpongostanTM and gauze sponge, and no noticeable effects of PA alone on the in vivo hemostatic performance of aerogels were observed; this may have been related to its poor diffusion from the aerogel matrix. Thus, PAs have a positive effect on hemostasis when incorporated into aerogels, although further studies should be conducted to elucidate the role of this extract in the different stages of hemostasis.

Loxin Reduced the Inflammatory Response in the Liver and the Aortic Fatty Streak Formation in Mice Fed with a High-Fat Diet.

Oxidized low-density lipoprotein (ox-LDL) is the most harmful form of cholesterol associated with vascular atherosclerosis and hepatic injury, mainly due to inflammatory cell infiltration and subsequent severe tissue injury. Lox-1 is the central ox-LDL receptor expressed in endothelial and immune cells, its activation regulating inflammatory cytokines and chemotactic factor secretion. Recently, a Lox-1 truncated protein isoform lacking the ox-LDL binding domain named LOXIN has been described. We have previously shown that LOXIN overexpression blocked Lox-1-mediated ox-LDL internalization in human endothelial progenitor cells in vitro. However, the functional role of LOXIN in targeting inflammation or tissue injury in vivo remains unknown. In this study, we investigate whether LOXIN modulated the expression of Lox-1 and reduced the inflammatory response in a high-fat-diet mice model. Results indicate that human LOXIN blocks Lox-1 mediated uptake of ox-LDL in H4-II-E-C3 cells. Furthermore, in vivo experiments showed that overexpression of LOXIN reduced both fatty streak lesions in the aorta and inflammation and fibrosis in the liver. These findings were associated with the down-regulation of Lox-1 in endothelial cells. Then, LOXIN prevents hepatic and aortic tissue damage in vivo associated with reduced Lox-1 expression in endothelial cells. We encourage future research to understand better the underlying molecular mechanisms and potential therapeutic use of LOXIN.

Novel and effective hemostats based on graphene oxide-polymer aerogels: In vitro and in vivo evaluation.

In this study, graphene oxide (GO)-based aerogels cross-linked with chitosan (CS), gelatin (GEL), and polyvinyl alcohol (PVA) were characterized and their hemostatic efficiencies both in vitro and in vivo were investigated and compared to commercial materials (ChitoGauze®XR and Spongostan™). All aerogels exhibited highly porous structures and a negative surface charge density favorable to their interaction with blood cells. The in vitro studies showed that all aerogels coagulated >60 % of the blood contained in their structures after 240 s of the whole-blood clotting assay, the GO-CS aerogel being the one with the highest blood clotting. All aerogels showed high hemocompatibility, with hemolytic rates <5 %, indicating their use as biomaterials. Among them, the GO-GEL aerogel exhibited the lowest hemolytic activity, due possibly to its high GEL content compared to the GO amount. According to their blood clotting activity, aerogels did not promote coagulation through extrinsic and intrinsic pathways. However, their surfaces are suitable for accelerating hemostasis by promoting alternative routes. All aerogels adhered platelets and gathered RBCs on their surfaces, and in addition the GO-CS aerogel surface also promoted the formation of filamentous fibrin networks adhered on its structure. Furthermore, in vivo evaluations revealed that all aerogels significantly shortened the hemostatic times and reduced the blood loss amounts compared both to the Spongostan™ and ChitoGauze®XR commercial materials and to the gauze sponge (control group). The hemostatic performance in vitro and in vivo of these aerogels suggests that they could be used as hemostats for controlling profuse bleedings.

Secretome from Human Mesenchymal Stem Cells-Derived Endothelial Cells Promotes Wound Healing in a Type-2 Diabetes Mouse Model.

Tissue regeneration is often impaired in patients with metabolic disorders such as diabetes mellitus and obesity, exhibiting reduced wound repair and limited regeneration capacity. We and others have demonstrated that wound healing under normal metabolic conditions is potentiated by the secretome of human endothelial cell-differentiated mesenchymal stem cells (hMSC-EC). However, it is unknown whether this effect is sustained under hyperglycemic conditions. In this study, the wound healing effect of secretomes from undifferentiated human mesenchymal stem cells (hMSC) and hMSC-EC in a type-2 diabetes mouse model was analyzed. hMSC were isolated from human Wharton's jelly and differentiated into hMSC-EC. hMSC and hMSC-EC secretomes were analyzed and their wound healing capacity in C57Bl/6J mice fed with control (CD) or high fat diet (HFD) was evaluated. Our results showed that hMSC-EC secretome enhanced endothelial cell proliferation and wound healing in vivo when compared with hMSC secretome. Five soluble proteins (angiopoietin-1, angiopoietin-2, Factor de crecimiento fibroblástico, Matrix metallopeptidase 9, and Vascular Endothelial Growth Factor) were enriched in hMSC-EC secretome in comparison to hMSC secretome. Thus, the five recombinant proteins were mixed, and their pro-healing property was evaluated in vitro and in vivo. Functional analysis demonstrated that a cocktail of these proteins enhanced the wound healing process similar to hMSC-EC secretome in HFD mice. Overall, our results show that hMSC-EC secretome or a combination of specific proteins enriched in the hMSC-EC secretome enhanced wound healing process under hyperglycemic conditions.

Carbamazepine Biosensor Development for Epilepsy Patient Screening.

The San Carlos population in Chile is an example of an underserved community due to lack of timely access to regular controls and laboratory results. One particular challenge is the adherence to treatment of Epilepsy patients. In this work, we present the design and proof-of-concept of a Point of Care Device (POCD) to measure carbamazepine levels in saliva to screen for correct dose prescription among epilepsy patients. We present the Screen Printed Electrode design and activating circuit and preliminary results to verify feasibility of the biosensor. Future steps include the fabrication of the device itself and validation with the target population.

Improved hemocompatibility for gelatin-graphene oxide composite aerogels reinforced with proanthocyanidins for wound dressing applications.

Aerogels based on gelatin and graphene oxide (GO) were synthesized by microwave-assisted reactions, incorporating grape skin extracts -high in proanthocyanidins (PAs)- to develop a hemostatic device with improved properties. The effects of incorporating PAs into the aerogels were investigated in relation to their physicochemical properties, absorption ability, clotting activity and cytotoxicity in human dermal fibroblast (HDF) cells. The aerogels presented highly resistant porous structures, capable of absorbing more than 50 times their weight when in contact with a phosphate saline solution (PBS) and fresh human blood. Interestingly, the addition of PAs increased the negative surface charges and the blood absorption ability of the aerogels, which may make them suitable for hemostasis. The incorporation of 5% and 10% (w/w) of extracts into the aerogels increased the total coagulated blood content by 36.6% and 24.5% compared with gelatin-GO aerogel, respectively. These improvements in the hemostatic properties of the aerogels were greater with the inclusion of 5% (w/w) of grape skin extracts into the aerogels. The aerogels were also able to adhere red blood cells onto their surfaces, which could favor the formation of stable fibrin networks to promote hemostasis. Their clotting activity suggested the activation of alternative routes based on complement coagulation systems. Finally, the aerogels were non-toxic for HDF cells and the PAs were successfully released from their matrices. Thus, gelatin-GO aerogels reinforced with PAs are promising as topical phytodrug delivery systems, with great potential for wound healing processes.

Preeclampsia and Increased Permeability Over the Blood-Brain Barrier: A Role of Vascular Endothelial Growth Receptor 2.

BACKGROUND: Cerebral complications in preeclampsia are leading causes of maternal mortality worldwide but pathophysiology is largely unknown and a challenge to study. Using an in vitro model of the human blood-brain barrier (BBB), we explored the role of vascular endothelial growth factor receptor 2 (VEGFR2) in preeclampsia. METHODS: The human brain endothelial cell line (hCMEC/D3) cultured on Tranwells insert was exposed (12 hours) to plasma from women with preeclampsia (n = 28), normal pregnancy (n = 28), and nonpregnant (n = 16) controls. Transendothelial electrical resistance (TEER) and permeability to 70 kDa fluorescein isothiocyanate (FITC)-dextran were measured for the assessment of BBB integrity. We explored possible underlying mechanisms, with a focus on the expression of tight junction proteins and phosphorylation of 2 tyrosine residues of VEGFR2, associated with vascular permeability and migration (pY951) and cell proliferation (pY1175). Plasma concentrations of soluble FMS-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were also measured. RESULTS: hCMEC/D3 exposed to plasma from women with preeclampsia exhibited reduced TEER and increased permeability to 70 kDa FITC-dextran. These cells upregulated the messenger ribonucleic acid (mRNA) levels of VEGFR2, and pY951-VEGFR2, but reduced pY1175-VEGFR2 (P < 0.05 in all cases). No difference in mRNA expression of tight junction protein was observed between groups. There was no correlation between angiogenic biomarkers and BBB permeability. CONCLUSIONS: We present a promising in vitro model of the BBB in preeclampsia. Selective tyrosine phosphorylation of VEGFR2 may participate in the increased BBB permeability in preeclampsia irrespective of plasma concentrations of angiogenic biomarkers.

Synthesis and characterization of graphene oxide chitosan aerogels reinforced with flavan-3-ols as hemostatic agents.

The natural mechanisms of the body cannot control massive hemorrhaging, resulting in a requirement for hemostatic intervention. In this study, Graphene oxide and Chitosan aerogels reinforced with grape seed (SD) and skin (SK) extracts were developed for use as hemostatic agents by evaluating the influence of pH on their synthesis, and the amount of grape extract added on the physical and chemical properties of the aerogels. The material was evaluated by FTIR, XRD, Raman spectroscopy, DLS, uniaxial compression tests and SEM. The capacity of the aerogels to absorb water, PBS and blood, as well as their coagulation capacity, were determined. In addition, the release profile for grape extracts in PBS and the material's cytotoxicity were determined. The aerogels that were synthesized under basic conditions and loaded with grape extracts were more rigid and negatively charged, and they presented smaller pores than the un-loaded acidic aerogels. For all aerogels, the hemoglobin absorption was greater than 90 % in the first 30 s. A higher density of adsorbed blood cells was observed on aerogels loaded with a higher amount of grape extract. The maximum release of extract from the aerogels occurred for those loaded with SK extracts at a basic pH; the aerogels that were prepared under acidic conditions dissolved in the media. Aerogels loaded with SK extracts under alkaline conditions were not cytotoxic toward human dermal fibroblasts and exhibited cell viabilities above 90 %. These findings suggest that these aerogels have the potential for use as hemostatic agents in wound management.

Advantages in Wound Healing Process in Female Mice Require Upregulation A2A-Mediated Angiogenesis under the Stimulation of 17ß-Estradiol.

Estrogenic steroids and adenosine A2A receptors promote the wound healing and angiogenesis processes. However, so far, it is unclear whether estrogen may regulate the expression and pro-angiogenic activity of A2A receptors. Using in vivo analyses, we showed that female wild type (WT) mice have a more rapid wound healing process than female or male A2A-deficient mice (A2AKO) mice. We also found that pulmonary endothelial cells (mPEC) isolated from female WT mice showed higher expression of A2A receptor than mPEC from male WT mice. mPEC from female WT mice were more sensitive to A2A-mediated pro-angiogenic response, suggesting an ER and A2A crosstalk, which was confirmed using cells isolated from A2AKO. In those female cells, 17ß-estradiol potentiated A2A-mediated cell proliferation, an effect that was inhibited by selective antagonists of estrogen receptors (ER), ERα, and ERß. Therefore, estrogen regulates the expression and/or pro-angiogenic activity of A2A adenosine receptors, likely involving activation of ERα and ERß receptors. Sexual dimorphism in wound healing observed in the A2AKO mice process reinforces the functional crosstalk between ER and A2A receptors.