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1.
Gels ; 10(7)2024 Jul 06.
Article in English | MEDLINE | ID: mdl-39057471

ABSTRACT

In this study, an innovative conductive hybrid biomaterial was synthetized using collagen (COL) and reduced graphene oxide (rGO) in order for it to be used as a wound dressing. The hydrogels were plasticized with glycerol and enzymatically cross-linked with horseradish peroxidase (HRP). A successful interaction among the components was demonstrated by FTIR, XRD, and XPS. It was demonstrated that increasing the rGO concentration led to higher conductivity and negative charge density values. Moreover, rGO also improved the stability of hydrogels, which was expressed by a reduction in the biodegradation rate. Furthermore, the hydrogel's stability against the enzymatic action of collagenase type I was also strengthened by both the enzymatic cross-linking and the polymerization of dopamine. However, their absorption capacity, reaching values of 215 g/g, indicates the high potential of the hydrogels to absorb fluids. The rise of these properties positively influenced the wound closure process, achieving an 84.5% in vitro closure rate after 48 h. These findings clearly demonstrate that these original composite biomaterials can be a viable choice for wound healing purposes.

2.
Biomedicines ; 12(6)2024 May 21.
Article in English | MEDLINE | ID: mdl-38927349

ABSTRACT

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.

3.
Polymers (Basel) ; 16(8)2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38675000

ABSTRACT

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.

4.
Biomacromolecules ; 24(11): 5183-5193, 2023 11 13.
Article in English | MEDLINE | ID: mdl-37906697

ABSTRACT

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.


Subject(s)
Chitosan , Chitosan/chemistry , Staphylococcus aureus , Escherichia coli , Tissue Scaffolds/chemistry , Bandages , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry
5.
Life Sci ; 333: 122166, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37827232

ABSTRACT

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.


Subject(s)
Ovarian Neoplasms , Humans , Female , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Drug Resistance, Neoplasm , Apoptosis , Cell Line, Tumor , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Glutathione/metabolism
6.
Int J Lab Hematol ; 45(6): 833-838, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37621152

ABSTRACT

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.


Subject(s)
Leukemia, Myeloid, Acute , Humans , Prognosis , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathology , Mutation , CCAAT-Enhancer-Binding Proteins/genetics , Transcription Factors/genetics
7.
Front Endocrinol (Lausanne) ; 14: 1130139, 2023.
Article in English | MEDLINE | ID: mdl-37274341

ABSTRACT

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.


Subject(s)
Abortion, Spontaneous , Pregnancy Complications , Premature Birth , Pregnancy , Infant, Newborn , Humans , Female , Cesarean Section , Machine Learning
8.
Polymers (Basel) ; 15(12)2023 Jun 20.
Article in English | MEDLINE | ID: mdl-37376399

ABSTRACT

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.

9.
Microvasc Res ; 148: 104498, 2023 07.
Article in English | MEDLINE | ID: mdl-36863509

ABSTRACT

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.


Subject(s)
Endothelial Progenitor Cells , Humans , Endothelial Progenitor Cells/metabolism , Adenosine/pharmacology , Adenosine/metabolism , Adenosine-5'-(N-ethylcarboxamide)/metabolism , Vascular Endothelial Growth Factor A/metabolism , Stem Cells/metabolism , Culture Media, Conditioned/metabolism
10.
Children (Basel) ; 10(3)2023 Feb 22.
Article in English | MEDLINE | ID: mdl-36979984

ABSTRACT

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.

11.
Metabolites ; 13(2)2023 Feb 16.
Article in English | MEDLINE | ID: mdl-36837911

ABSTRACT

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.

12.
Pharmaceutics ; 14(9)2022 Aug 25.
Article in English | MEDLINE | ID: mdl-36145521

ABSTRACT

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.

13.
Biomater Adv ; 139: 213007, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35891602

ABSTRACT

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.


Subject(s)
Chitosan , Graphite , Hemostatics , Chitosan/chemistry , Gelatin/pharmacology , Graphite/pharmacology , Hemorrhage , Hemostatics/pharmacology , Humans , Polymers
14.
Int J Mol Sci ; 23(13)2022 Jun 30.
Article in English | MEDLINE | ID: mdl-35806336

ABSTRACT

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.


Subject(s)
Atherosclerosis , Endothelial Progenitor Cells , Phthalazines , Animals , Aorta/metabolism , Aorta/pathology , Atherosclerosis/drug therapy , Atherosclerosis/etiology , Atherosclerosis/metabolism , Atherosclerosis/pathology , Cells, Cultured , Diet, High-Fat/adverse effects , Endothelial Progenitor Cells/drug effects , Endothelial Progenitor Cells/metabolism , Endothelial Progenitor Cells/pathology , Inflammation/drug therapy , Inflammation/genetics , Inflammation/metabolism , Inflammation/pathology , Lipoproteins, LDL/metabolism , Liver/metabolism , Mice , Phthalazines/pharmacology , Scavenger Receptors, Class E/genetics , Scavenger Receptors, Class E/metabolism
15.
Int J Mol Sci ; 23(2)2022 Jan 15.
Article in English | MEDLINE | ID: mdl-35055129

ABSTRACT

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.


Subject(s)
Culture Media, Conditioned/pharmacology , Diabetes Mellitus, Type 2/metabolism , Mesenchymal Stem Cells/cytology , Recombinant Proteins/pharmacology , Wound Healing/drug effects , Angiopoietin-1/metabolism , Angiopoietin-1/pharmacology , Angiopoietin-2/metabolism , Angiopoietin-2/pharmacology , Animals , Cell Differentiation , Cell Proliferation , Cells, Cultured , Culture Media, Conditioned/chemistry , Diabetes Mellitus, Type 2/chemically induced , Diet, High-Fat/adverse effects , Disease Models, Animal , Humans , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase 9/pharmacology , Mesenchymal Stem Cells/metabolism , Mice , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/pharmacology , Wharton Jelly/cytology , Wharton Jelly/metabolism
16.
Colloids Surf B Biointerfaces ; 206: 111941, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34216847

ABSTRACT

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.


Subject(s)
Graphite , Proanthocyanidins , Bandages , Gelatin , Humans , Proanthocyanidins/pharmacology
17.
Int J Mol Sci ; 21(19)2020 Sep 28.
Article in English | MEDLINE | ID: mdl-32998232

ABSTRACT

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.


Subject(s)
Estradiol/pharmacology , Estrogen Receptor alpha/genetics , Estrogen Receptor beta/genetics , Neovascularization, Physiologic/drug effects , Receptor, Adenosine A2A/genetics , Wounds, Penetrating/genetics , Adenosine/analogs & derivatives , Adenosine/pharmacology , Animals , Cell Proliferation/drug effects , Endothelial Cells/cytology , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Estrogen Receptor alpha/antagonists & inhibitors , Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/antagonists & inhibitors , Estrogen Receptor beta/metabolism , Female , Gene Expression Regulation , Lung/cytology , Lung/metabolism , Male , Mice , Mice, Knockout , Neovascularization, Physiologic/genetics , Phenethylamines/pharmacology , Pyrazoles/pharmacology , Pyrimidines/pharmacology , Receptor Cross-Talk , Receptor, Adenosine A2A/metabolism , Sex Factors , Signal Transduction , Wound Healing/drug effects , Wound Healing/genetics , Wounds, Penetrating/drug therapy , Wounds, Penetrating/metabolism , Wounds, Penetrating/pathology
18.
Purinergic Signal ; 16(3): 427-437, 2020 09.
Article in English | MEDLINE | ID: mdl-32808144

ABSTRACT

We aim to investigate the role of A2A receptor in peritonitis-related sepsis by injection of a fecal solution (FS) as a model of polymicrobial infection. C57/black J6 wild-type (WT) and A2A-deficient mice (A2AKO) were exposed to sepsis induced by intraperitoneal injection of a FS (FS-induced peritonitis) or instead was injected with saline buffer (Sham). Survival rate and sepsis score were measured up to 48 h. The presence of bacteria in tissue homogenates was analyzed. Telemetry and speckle laser Doppler were used for systemic blood pressure and peripheral blood perfusion analysis, respectively. Histological analysis and identification of active caspase 3 were performed in selected organs, including the liver. The survival rate of A2AKO mice exposed to FS-induced peritonitis was significantly higher, and the sepsis score was lower than their respective WT counterpart. Injection of FS increases (50 to 150 folds) the number of colonies forming units in the liver, kidney, blood, and lung in WT mice, while these effects were significantly attenuated in A2AKO mice exposed to FS-induced peritonitis. A significant reduction in both systolic and diastolic blood pressure, as well as in the peripheral perfusion was observed in WT and A2AKO mice exposed to FS-induced peritonitis. Although, these last effects were significantly attenuated in A2AKO mice. Histological analysis showed a large perivascular infiltration of polymorphonuclear in the liver of WT and A2AKO mice exposed to FS-induced peritonitis, but again, this effect was attenuated in A2AKO mice. Finally, high expression of active caspase 3 was found only in the liver of WT mice exposed to FS-induced peritonitis. The absence of the A2A receptor increases the survival rate in mice exposed to polymicrobial sepsis. This outcome was associated with both hemodynamic compensation and enhanced anti-bacterial response.


Subject(s)
Peritonitis/metabolism , Receptor, Adenosine A2A/metabolism , Sepsis/metabolism , Animals , Blood Pressure/physiology , Disease Models, Animal , Mice , Mice, Knockout , Peritonitis/genetics , Peritonitis/microbiology , Peritonitis/mortality , Receptor, Adenosine A2A/genetics , Sepsis/genetics , Sepsis/mortality , Survival Rate
19.
Int J Nanomedicine ; 15: 1229-1238, 2020.
Article in English | MEDLINE | ID: mdl-32110019

ABSTRACT

INTRODUCTION: In the last years, the utilization of phytomedicines has increased given their good therapeutic activity and fewer side effects compared to allopathic medicines. However, concerns associated with the biocompatibility and toxicity of natural compounds, limit the phytochemical therapeutic action, opening the opportunity to develop new systems that will be able to effectively deliver these substances. This study has developed a nanocomposite of chitosan (CS) functionalized with graphene oxide (GO) for the delivery of proanthocyanidins (PAs), obtained from a grape seed extract (Ext.). METHODS: The GO-CS nanocomposite was covalently bonded and was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), atomic force microscopy (AFM) and by dynamic light scattering (DLS). The loading and release of Ext. from the GO-CS nanocomposite were performed in simulated physiological, and the cytotoxicity of the raw materials (GO and Ext.) and nanocomposites (GO-CS and GO-CS-Ext.) was determined using a human kidney cell line (HEK 293). RESULTS: The chemical characterization indicated that the covalent union was successfully achieved between the GO and CS, with 44 wt. % CS in the nanocomposite. The GO-CS nanocomposite was thermostable and presented an average diameter of 480 nm (by DLS). The Ext. loading capacity was approximately 20 wt. %, and under simulated physiological conditions, 28.4 wt.% Ext. (g) was released per g of the nanocomposite. GO-CS-Ext. was noncytotoxic, presenting a 97% survival rate compared with 11% for the raw extract and 48% for the GO-CS nanocomposite at a concentration of 500 µg mL-1 after 24 hrs. CONCLUSION: Due to π-π stacking and hydrophilic interactions, GO-CS was reasonably efficient in binding Ext., with high loading capacity and Ext. release from the nanocomposite. The GO-CS nanocomposite also increased the biocompatibility of PAs-rich Ext., representing a new platform for the sustained release of phytodrugs.


Subject(s)
Nanocomposites/administration & dosage , Nanocomposites/chemistry , Proanthocyanidins/administration & dosage , Chitosan/chemistry , Drug Delivery Systems/methods , Grape Seed Extract/administration & dosage , Grape Seed Extract/chemistry , Grape Seed Extract/isolation & purification , Graphite/chemistry , HEK293 Cells , Humans , Microscopy, Electron, Scanning , Photoelectron Spectroscopy , Proanthocyanidins/isolation & purification , Spectroscopy, Fourier Transform Infrared
20.
Biosensors (Basel) ; 9(1)2019 Feb 27.
Article in English | MEDLINE | ID: mdl-30818887

ABSTRACT

Rheumatoid arthritis (RA) has been associated with a higher risk of developing cardiovascular (CV) diseases. It has been proposed that systemic inflammation plays a key role in premature atherosclerosis development, and is therefore crucial to determine whether systemic components from RA patients promotes endothelial cell-oxidative stress by affecting reactive oxygen species (ROS) and nitric-oxide (NO) production. The aim of this study was to evaluate whether plasma from RA patients impair NO synthesis and ROS production by using the cell-line ECV-304 as a biosensor. NO synthesis and ROS production were measured in cells incubated with plasma from 73 RA patients and 52 healthy volunteers by fluorimetry. In addition, traditional CV risk factors, inflammatory molecules and disease activity parameters were measured. Cells incubated with plasma from RA patients exhibited reduced NO synthesis and increased ROS production compared to healthy volunteers. Furthermore, the imbalance between NO synthesis and ROS generation in RA patients was not associated with traditional CV risk factors. Our data suggest that ECV-304 cells can be used as a biosensor of systemic inflammation-induced endothelial cell-oxidative stress. We propose that both NO and ROS production are potential biomarkers aimed at improving the current assessment of CV risk in RA.


Subject(s)
Biosensing Techniques , Inflammation/blood , Nitric Oxide/isolation & purification , Plasma , Arthritis, Rheumatoid/blood , Atherosclerosis/blood , Atherosclerosis/pathology , Cell Line , Endothelial Cells/drug effects , Humans , Inflammation/pathology , Nitric Oxide/biosynthesis , Oxidative Stress/drug effects , Reactive Oxygen Species/chemistry , Reactive Oxygen Species/isolation & purification
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