RESUMEN
Antigen cross-presentation, wherein dendritic cells (DCs) present exogenous antigen on major histocompatibility class I (MHC-I) molecules, is considered the primary mechanism by which DCs initiate tumor-specific CD8+ T cell responses. Here, we demonstrate that MHC-I cross-dressing, an antigen presentation pathway in which DCs acquire and display intact tumor-derived peptide:MHC-I molecules, is also important in orchestrating anti-tumor immunity. Cancer cell MHC-I expression was required for optimal CD8+ T cell activation in two subcutaneous tumor models. In vivo acquisition of tumor-derived peptide:MHC-I molecules by DCs was sufficient to induce antigen-specific CD8+ T cell priming. Transfer of tumor-derived human leukocyte antigen (HLA) molecules to myeloid cells was detected in vitro and in human tumor xenografts. In conclusion, MHC-I cross-dressing is crucial for anti-tumor CD8+ T cell priming by DCs. In addition to quantitatively enhancing tumor antigen presentation, MHC cross-dressing might also enable DCs to more faithfully and efficiently mirror the cancer cell peptidome.
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Células Dendríticas , Neoplasias , Presentación de Antígeno , Antígenos de Neoplasias , Vendajes , Linfocitos T CD8-positivos , Reactividad Cruzada , Antígenos de Histocompatibilidad Clase I , Humanos , Complejo Mayor de Histocompatibilidad , Neoplasias/metabolismo , PéptidosRESUMEN
The competition-colonization (CC) trade-off is a well-studied coexistence mechanism for metacommunities. In this setting, it is believed that the coexistence of all species requires their traits to satisfy restrictive conditions limiting their similarity. To investigate whether diverse metacommunities can assemble in a CC trade-off model, we study their assembly from a probabilistic perspective. From a pool of species with parameters (corresponding to traits) sampled at random, we compute the probability that any number of species coexist and characterize the set of species that emerges through assembly. Remarkably, almost exactly half of the species in a large pool typically coexist, with no saturation as the size of the pool grows, and with little dependence on the underlying distribution of traits. Through a mix of analytical results and simulations, we show that this unlimited niche packing emerges as assembly actively moves communities toward overdispersed configurations in niche space. Our findings also apply to a realistic assembly scenario where species invade one at a time from a fixed regional pool. When diversity arises de novo in the metacommunity, richness still grows without bound, but more slowly. Together, our results suggest that the CC trade-off can support the robust emergence of diverse communities, even when coexistence of the full species pool is exceedingly unlikely.
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Vendajes , Fenotipo , ProbabilidadRESUMEN
Sponges (Porifera) contain many peptide-specialized metabolites with potent biological activities and significant roles in shaping marine ecology. It is well established that symbiotic bacteria produce bioactive "sponge" peptides, both on the ribosome (RiPPs) and nonribosomally. Here, we demonstrate that sponges themselves also produce many bioactive macrocyclic peptides, such as phakellistatins and related proline-rich macrocyclic peptides (PRMPs). Using the Stylissa carteri sponge transcriptome, methods were developed to find sequences encoding 46 distinct RiPP-type core peptides, of which ten encoded previously identified PRMP sequences. With this basis set, the genome and transcriptome of the sponge Axinella corrugata was interrogated to find 35 PRMP precursor peptides encoding 31 unique core peptide sequences. At least 11 of these produced cyclic peptides that were present in the sponge and could be characterized by mass spectrometry, including stylissamides A-D and seven previously undescribed compounds. Precursor peptides were encoded in the A. corrugata genome, confirming their animal origin. The peptides contained signal peptide sequences and highly repetitive recognition sequence-core peptide elements with up to 25 PRMP copies in a single precursor. In comparison to sponges without PRMPs, PRMP sponges are incredibly enriched in potentially secreted polypeptides, with >23,000 individual signal peptide encoding genes found in a single transcriptome. The similarities between PRMP biosynthetic genes and neuropeptides in terms of their biosynthetic logic suggest a fundamental biology linked to circular peptides, possibly indicating a widespread and underappreciated diversity of signaling peptide post-translational modifications across the animal kingdom.
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Péptidos Cíclicos , Péptidos , Animales , Péptidos/genética , Péptidos Cíclicos/genética , Secuencia de Aminoácidos , Vendajes , Señales de Clasificación de ProteínaRESUMEN
The exploitation of novel wound healing methods with real-time infection sensing and high spatiotemporal precision is highly important for human health. Pt-based metal-organic cycles/cages (MOCs) have been employed as multifunctional antibacterial agents due to their superior Pt-related therapeutic efficiency, various functional subunits and specific geometries. However, how to rationally apply these nanoscale MOCs on the macroscale with controllable therapeutic output is still challenging. Here, a centimeter-scale Pt MOC film was constructed via multistage assembly and subsequently coated on a N,N'-dimethylated dipyridinium thiazolo[5,4-d]thiazole (MPT)-stained silk fabric to form a smart wound dressing for bacterial sensing and wound healing. The MPT on silk fabric could be used to monitor wound infection in real-time through the bacteria-mediated reduction of MPT to its radical form via a color change. The MPT radical also exhibited an excellent photothermal effect under 660 nm light irradiation, which could not only be applied for photothermal therapy but also induce the disassembly of the Pt MOC film suprastructure. The highly ordered Pt MOC film suprastructure exhibited high biosafety, while it also showed improved antibacterial efficiency after thermally induced disassembly. In vitro and in vivo studies revealed that the combination of the Pt MOC film and MPT-stained silk can provide real-time information on wound infection for timely treatment through noninvasive techniques. This study paves the way for bacterial sensing and wound healing with centimeter-scale metal-organic materials.
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Platino (Metal) , Infección de Heridas , Humanos , Platino (Metal)/farmacología , Cicatrización de Heridas , Vendajes , Antibacterianos/farmacología , Antibacterianos/química , Seda/química , Bacterias , Hidrogeles/farmacologíaRESUMEN
A twin boundary (TB) is a common low energy planar defect in crystals including those with the atomic diamond structure (C, Si, Ge, etc.). We study twins in a self-assembled soft matter block copolymer (BCP) supramolecular crystal having the double diamond (DD) structure, consisting of two translationally shifted, interpenetrating diamond networks of the minority polydimethyl siloxane block embedded in a polystyrene block matrix. The coherent, low energy, mirror-symmetric double tubular network twin has one minority block network with its nodes offset from the (222) TB plane, while nodes of the second network lie in the plane of the boundary. The offset network, although at a scale about a factor of 103 larger, has precisely the same geometry and symmetry as a (111) twin in atomic single diamond where the tetrahedral units spanning the TB retain nearly the same strut (bond) lengths and strut (bond) angles as in the normal unit cell. In DD, the second network undergoes a dramatic restructuring-the tetrahedral nodes transform into two new types of mirror-symmetric nodes (pentahedral and trihedral) which alternate and link to form a hexagonal mesh in the plane of the TB. The collective reorganization of the supramolecular packing highlights the hierarchical structure of ordered BCP phases and emphasizes the remarkable malleability of soft matter.
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Vendajes , Diamante , Grupos Minoritarios , Polímeros , PoliestirenosRESUMEN
Efficient generation of tissue-resident memory T (TRM) cells is essential for long-lived immune protection in barrier tissues. Peng et al. now show that the costimulatory molecule ICOS enhances CD8+ TRM cell lodgment by promoting early tissue retention.
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Internado y Residencia , Vendajes , Linfocitos T CD8-positivos/inmunología , Humanos , Memoria Inmunológica/inmunología , Proteína Coestimuladora de Linfocitos T Inducibles , Factores de TranscripciónRESUMEN
Diabetic foot ulcer (DFU) is one of the most costly and serious complications of diabetes. Treatment of DFU is usually challenging and new approaches are required to improve the therapeutic efficiencies. This review aims to update new and upcoming adjunctive therapies with noninvasive characterization for DFU, focusing on bioactive dressings, bioengineered tissues, mesenchymal stem cell (MSC) based therapy, platelet and cytokine-based therapy, topical oxygen therapy, and some repurposed drugs such as hypoglycemic agents, blood pressure medications, phenytoin, vitamins, and magnesium. Although the mentioned therapies may contribute to the improvement of DFU to a certain extent, most of the evidence come from clinical trials with small sample size and inconsistent selections of DFU patients. Further studies with high design quality and adequate sample sizes are necessitated. In addition, no single approach would completely correct the complex pathogenesis of DFU. Reasonable selection and combination of these techniques should be considered.
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Pie Diabético , Humanos , Pie Diabético/terapia , Pie Diabético/tratamiento farmacológico , Vendajes , AnimalesRESUMEN
The growing threat of antibiotic-resistant bacterial pathogens necessitates the development of alternative antimicrobial approaches. This is particularly true for chronic wound infections, which commonly harbor biofilm-dwelling bacteria. A novel electrochemical bandage (e-bandage) delivering low-levels of hypochlorous acid (HOCl) was evaluated against Pseudomonas aeruginosa murine wound biofilms. 5 mm skin wounds were created on the dorsum of mice and infected with 106 colony-forming units (CFU) of P. aeruginosa. Biofilms were formed over 2 days, after which e-bandages were placed on the wound beds and covered with Tegaderm. Mice were administered Tegaderm-only (control), non-polarized e-bandage (no HOCl production), or polarized e-bandage (using an HOCl-producing potentiostat), with or without systemic amikacin. Purulence and wound areas were measured before and after treatment. After 48 hours, wounds were harvested for bacterial quantification. Forty-eight hours of polarized e-bandage treatment resulted in mean biofilm reductions of 1.4 log10 CFUs/g (P = 0.0107) vs non-polarized controls and 2.2 log10 CFU/g (P = 0.004) vs Tegaderm-only controls. Amikacin improved CFU reduction in Tegaderm-only (P = 0.0045) and non-polarized control groups (P = 0.0312) but not in the polarized group (P = 0.3876). Compared to the Tegaderm-only group, there was less purulence in the polarized group (P = 0.009). Wound closure was neither impeded nor improved by either polarized or non-polarized e-bandage treatment. Concurrent amikacin did not impact wound closure or purulence. In conclusion, an HOCl-producing e-bandage reduced P. aeruginosa in wound biofilms with no impairment in wound healing, representing a promising antibiotic-free approach for addressing wound infection.
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Infecciones por Pseudomonas , Infección de Heridas , Animales , Ratones , Pseudomonas aeruginosa , Ácido Hipocloroso , Amicacina , Infecciones por Pseudomonas/microbiología , Infección de Heridas/microbiología , Vendajes , Antibacterianos , BiopelículasRESUMEN
Chronic skin wounds decrease the quality of life of millions of diabetic patients worldwide. Chitosan has previously been shown to possess hemostatic properties, decrease inflammation, promote fibroblast proliferation, and hair growth. We developed a relatively low-cost polyelectrolyte complex (PEC) film dressing made of chitosan and polygalacturonic acid and tested it for its ability to accelerate diabetic wound healing. Genetically diabetic male mice were shaved on the dorsum, and one day later a 1 cm diameter full-thickness excisional wound was created. The PEC film was applied immediately after wounding and left in place for 14 days. Controls consisted of wounds treated with a fibrin gel. Wounds covered with the PEC film had closed completely by post-wounding day 42, while untreated wounds were only half-way closed. Histological analysis of wounds confirmed that PEC-treated wounds had fully re-epithelialized, while control wounds lacked a continuous epidermis at the wound center. We also observed that the area of skin under the PEC film experienced much more rapid hair growth. Histologically, there were significantly more hair follicles around the scar area (p < 0.05) in the PEC-treated group as compared to the control group. Thus, chitosan-polygalacturonic acid PEC films can accelerate both wound healing and hair growth in diabetic mice, and should be further investigated as a potential future treatment for diabetic chronic wounds.
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Quitosano , Diabetes Mellitus Experimental , Pectinas , Humanos , Ratones , Masculino , Animales , Diabetes Mellitus Experimental/complicaciones , Calidad de Vida , Cicatrización de Heridas , Vendajes , CabelloRESUMEN
The treatment of chronic wounds still presents great challenges due to being infected by biofilms and the damaged healing process. The current treatments do not address the needs of chronic wounds. In this study, a highly effective dressing (Dox-DFO@MN Hy) for the treatment of chronic wounds is described. This dressing combines the advantages of microneedles (MNs) and hydrogels in the treatment of chronic wounds. MNs is employed to debride the biofilms and break down the wound barrier, providing rapid access to therapeutic drugs from hydrogel backing layer. Importantly, to kill the pathogenic bacteria in the biofilms specifically, Doxycycline hydrochloride (Dox) is wrapped into the polycaprolactone (PCL) microspheres that have lipase-responsive properties and loaded into the tips of MNs. At the same time, hydrogel backing layer is used to seal the wound and accelerate wound healing. Benefiting from the combination of two advantages of MNs and hydrogel, the dressing significantly reduces the bacteria in the biofilms and effectively promotes angiogenesis and cell migration in vitro. Overall, Dox-DFO@MN Hy can effectively treat chronic wounds infected with biofilms, providing a new idea for the treatment of chronic wounds.
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Vendajes , Hidrogeles , Bacterias , Biopelículas , Movimiento Celular , Antibacterianos/farmacología , Antibacterianos/uso terapéuticoRESUMEN
Tissue development is mediated by a combination of mechanical and biological signals. Currently, there are many reports on biological signals regulating repair. However, insufficient attention is paid to the process of mechanical regulation, especially the active mechanical regulation in vivo, which has not been realized. Herein, a novel dynamically regulated repair system for both in vitro and in vivo applications is developed, which utilizes magnetic nanoparticles as non-contact actuators to activate hydrogels. The magnetic hydrogel can be periodically activated and deformed to different amplitudes by a dynamic magnetic system. An in vitro skin model is used to explore the impact of different dynamic stimuli on cellular mechano-transduction signal activation and cell differentiation. Specifically, the effect of mechanical stimulation on the phenotypic transition of fibroblasts to myofibroblasts is investigated. Furthermore, in vivo results verify that dynamic massage can simulate and enhance the traction effect in skin defects, thereby accelerating the wound healing process by promoting re-epithelialization and mediating dermal contraction.
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Vendajes , Masaje , Cicatrización de Heridas , Animales , Masaje/métodos , Fibroblastos , Humanos , Hidrogeles/química , Diferenciación Celular , Piel , Ratones , Miofibroblastos/citologíaRESUMEN
Microbial infections based on drug-resistant pathogenic organisms following surgery or trauma and uncontrolled bleeding are the main causes of increased mortality from trauma worldwide. The prevalence of drug-resistant pathogens has led to a significant increase in medical costs and poses a great threat to the normal life of people. This is an important issue in the field of biomedicine, and the emergence of new antimicrobial materials hydrogels holds great promise for solving this problem. Hydrogel is an important material with good biocompatibility, water absorption, oxygen permeability, adhesion, degradation, self-healing, corrosion resistance, and controlled release of drugs as well as structural diversity. Bacteria-disturbing hydrogels have important applications in the direction of surgical treatment, wound dressing, medical device coating, and tissue engineering. This paper reviews the classification of antimicrobial hydrogels, the current status of research, and the potential of antimicrobial hydrogels for one application in biomedicine, and analyzes the current research of hydrogels in biomedical applications from five aspects: metal-loaded hydrogels, drug-loaded hydrogels, carbon-material-loaded hydrogels, hydrogels with fixed antimicrobial activity and biological antimicrobial hydrogels, and provides an outlook on the high antimicrobial activity, biodegradability, biocompatibility, injectability, clinical applicability and future development prospects of hydrogels in this field.
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Antiinfecciosos , Hidrogeles , Humanos , Hidrogeles/química , Antiinfecciosos/farmacología , Bacterias , Vendajes , Antibacterianos/químicaRESUMEN
In recent years, there has been growing interest in developing innovative materials and therapeutic strategies to enhance wound healing outcomes, especially for chronic wounds and antimicrobial resistance. Metal-organic frameworks (MOFs) represent a promising class of materials for next-generation wound healing and dressings. Their high surface area, pore structures, stimuli-responsiveness, antibacterial properties, biocompatibility, and potential for combination therapies make them suitable for complex wound care challenges. MOF-based composites promote cell proliferation, angiogenesis, and matrix synthesis, acting as carriers for bioactive molecules and promoting tissue regeneration. They also have stimuli-responsivity, enabling photothermal therapies for skin cancer and infections. Herein, a critical analysis of the current state of research on MOFs and MOF-based composites for wound healing and dressings is provided, offering valuable insights into the potential applications, challenges, and future directions in this field. This literature review has targeted the multifunctionality nature of MOFs in wound-disease therapy and healing from different aspects and discussed the most recent advancements made in the field. In this context, the potential reader will find how the MOFs contributed to this field to yield more effective, functional, and innovative dressings and how they lead to the next generation of biomaterials for skin therapy and regeneration.
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Vendajes , Estructuras Metalorgánicas , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Humanos , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacologíaRESUMEN
Complex wound repair due to tumor recurrence and infection following tumor resection presents significant clinical challenges. In this study, a bifunctional nanocomposite immune hydrogel dressing, SerMA-LJC, is developed to address the issues associated with repairing infected damaged tissues and preventing tumor recurrence. Specifically, the immune dressing is composed of methacrylic anhydride-modified sericin (SerMA) and self-assembled nanoparticles (LJC) containing lonidamine (Lon), JQ1, and chlorine e6 (Ce6). In vitro and in vivo experiments demonstrate that the nanocomposite hydrogel dressing can trigger immunogenic cell death (ICD) and has a potent anti-tumor effect. Moreover, this dressing can mitigate the acidic microenvironment of tumor cells and suppress the overexpression of PD-L1 on the tumor cell surface, thereby altering the immunosuppressive tumor microenvironment and augmenting the anti-tumor immune response. Further, the RNA sequencing analysis revealed that the hydrogel dressing significantly impacts pathways associated with positive regulation of immune response, apoptotic process, and other relevant pathways, thus triggering a potent anti-tumor immune response. More importantly, the dressing generates a substantial amount of reactive oxygen species (ROS), which can effectively kill Staphylococcus aureus and promote infectious wound healing. In conclusion, this dual-function nanocomposite immune hydrogel dressing exhibits promise in preventing tumor recurrence and promoting infectious wound healing.
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Nanocompuestos , Nanocompuestos/química , Animales , Recurrencia Local de Neoplasia/prevención & control , Ratones , Hidrogeles/química , Vendajes , Melanoma/patología , Línea Celular Tumoral , Staphylococcus aureus/efectos de los fármacos , Humanos , Inyecciones , Microambiente Tumoral/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Topical hemostatic agents are preferred for application to sensitive bleeding sites because of their immediate locoregional effects with less tissue damage. However, the majority of commercial hemostatic agents fail to provide stable tissue adhesion to bleeding wounds or act as physical barriers against contaminants. Hence, it has become necessary to investigate biologically favorable materials that can be applied and left within the body post-surgery. In this study, a dual-sided nanofibrous dressing for topical hemostasis is electrospun using a combination of two protein materials: bioengineered mussel adhesive protein (MAP) and silk fibroin (SF). The wound-adhesive inner layer is fabricated using dihydroxyphenylalanine (DOPA)-containing MAP, which promotes blood clotting by aggregation of hemocytes and activation of platelets. The anti-adhesive outer layer is composed of alcohol-treated hydrophobic SF, which has excellent spinnability and mechanical strength for fabrication. Because both proteins are fully biodegradable in vivo and biocompatible, the dressing would be suitable to be left in the body. Through in vivo evaluation using a rat liver damage model, significantly reduced clotting time and blood loss are confirmed, successfully demonstrating that the proposed dual-sided nanofibrous dressing has the right properties and characteristics as a topical hemostatic agent having dual functionality of hemostasis and physical protection.
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Antibacterianos , Vendajes , Hemostasis , Hemostáticos , Nanofibras , Animales , Nanofibras/química , Hemostasis/efectos de los fármacos , Hemostáticos/química , Hemostáticos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Ratas , Fibroínas/química , Fibroínas/farmacología , Bivalvos/química , Proteínas/química , Seda/química , Ratas Sprague-DawleyRESUMEN
The field of clinical surgery frequently encounters challenges related to atypical wound tissue healing, resulting in the development of persistent chronic wounds or aesthetically displeasing scar tissue. The use of wound dressings crafted from mussel adhesive proteins and hyaluronic acid has demonstrated the potential in mitigating these undesirable outcomes. However, the synergistic effects of these two biomaterials remain underexplored. In this study, we have engineered a versatile, degradable, and biocompatible dressing that comprises recombinant 3,4-dihydroxyphenylalanine (DOPA)-modified mussel adhesive proteins and maleimide-functionalized hyaluronic acid. We have successfully fabricated this biocompatible dressing and conducted comprehensive experimental assessments to confirm its hemostatic, antibacterial, and biocompatible characteristics. Importantly, this dressing exclusively incorporates biologically derived materials characterized by low toxicity and minimal immunogenicity, thus holding immense promise for clinical applications in the field of wound healing.
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Hemostáticos , Hemostáticos/farmacología , Hemostáticos/uso terapéutico , Cisteína , Ácido Hialurónico , Antibacterianos/farmacología , Vendajes , MaleimidasRESUMEN
PURPOSE: Radiation-induced skin reactions remain one of the most frequent side effects of adjuvant radiotherapy for breast cancer, which is the most common global malignancy. In individual cases, we observed a decrease in radiation dermatitis under film dressings used for skin marking purposes. Therefore, we decided to revise the available evidence regarding the prophylactic use of film dressings to reduce radiation dermatitis in breast cancer patients. METHODS: On 20 March 2023, we conducted a systematic review of literature for randomized controlled trials published in the English, German, French, or Spanish language, available in the PubMed database. RESULTS: Of 82 publications, 9 full texts were assessed and 6 randomized controlled trials were included in the final synthesis. Two trials analyzed the application of polyurethane film (Hydrofilm, Paul Hartmann AG, Heidenheim, Germany), the other four of silicone-based polyurethane film (Mepitel film, Molnlycke Health Care Limited, Milton Keynes, United Kingdom). The evaluation scales Common Terminology Criteria for Adverse Events (CTCAE), Radiation Therapy Oncology Group (RTOG), and the Radiation-Induced Skin Reaction Assessment Scale (RISRAS) were used for assessment. All six trials, with a total of 788 patients yielding data for analysis, demonstrate a significant decrease in radiation-induced skin reactions by use of the film (mainly pâ¯< 0.001). CONCLUSION: Our analysis demonstrates a significant decrease in radiation-induced skin reactions by prophylactically applied film dressings in breast cancer patients. Consequent preventive use of film dressings might systematically reduce acute radiation-induced skin reactions in these patients.
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Neoplasias de la Mama , Neoplasias Inducidas por Radiación , Radiodermatitis , Humanos , Femenino , Neoplasias de la Mama/radioterapia , Poliuretanos , Vendajes , Mama , Radiodermatitis/etiología , Radiodermatitis/prevención & controlRESUMEN
Healing of complex wounds requires dressings that must, at least, not hinder and should ideally promote the activity of key healing cells, in particular fibroblasts. This in vitro study assessed the effects of three wound-dressings (a pure Ca2+ alginate: Algostéril®, a Ca2+ alginate + carboxymethylcellulose: Biatain alginate® and a polyacrylate impregnated with lipido-colloid matrix: UrgoClean®) on dermal fibroblast activity. The results showed the pure calcium alginate to be non-cytotoxic, whereas the other wound-dressings showed moderate to strong cytotoxicity. The two alginates stimulated fibroblast migration and proliferation, whereas the polyacrylate altered migration and had no effect on proliferation. The pure Ca2+ alginate significantly increased the TGF-ß-induced fibroblast activation, which is essential to healing. This activation was confirmed by a significant increase in Vascular endothelial growth factor (VEGF) secretion and a higher collagen production. The other dressings reduced these fibroblast activities. The pure Ca2+ alginate was also able to counteract the inhibitory effect of NK cell supernatants on fibroblast migration. These in vitro results demonstrate that tested wound-dressings are not equivalent for fibroblast activation. Only Algostéril was found to promote all the fibroblast activities tested, which could contribute to its healing efficacy demonstrated in the clinic.
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Alginatos , Movimiento Celular , Proliferación Celular , Fibroblastos , Factor A de Crecimiento Endotelial Vascular , Cicatrización de Heridas , Fibroblastos/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Humanos , Alginatos/farmacología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Colágeno/metabolismo , Vendajes , Factor de Crecimiento Transformador beta/metabolismo , Carboximetilcelulosa de Sodio , Células Cultivadas , Células Asesinas Naturales/efectos de los fármacos , Resinas Acrílicas , Ácidos Hexurónicos , Ácido Glucurónico , PielRESUMEN
BACKGROUND: Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer (BC). The circRNA-miRNAâmRNA axis is a promising biomarker for the early diagnosis and prognosis of BC. However, the critical circRNA mediators involved in TNBC progression and the underlying regulatory mechanism involved remain largely unclear. METHODS: In this study, we carried out a circRNA microarray analysis of 6 TNBC patients and performed a gene ontology (GO) analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to characterize important circRNAs involved in TNBC progression. The interaction between circRNAs and miRNAs was determined by dual luciferase and RNA immunoprecipitation (RIP) assays. Moreover, Transwell, wound healing and Cell Counting Kit-8 (CCK8) assays were performed with altered circRNA or miRNA expression in MDA-MB-231 and BT-549 cells to investigate the roles of these genes in cell invasion, migration and proliferation. RESULTS: A total of 78 circRNAs were differentially expressed in TNBC tissues, and the hsa_circ_0045881 level was significantly decreased in TNBC tissues and cells. Lentivirus-mediated hsa_circ_0045881 overexpression in MDA-MB-231 and BT-549 cells significantly reduced cell invasion and migration capacity. Additionally, hsa_circ_0045881 interacted with miR-214-3p in MDA-MB-231 cells. miR-214-3p mimics in MDA-MB-231 and BT-549 cells significantly enhanced cell invasion, migration and proliferation, but the other combinations of inhibitors had opposite effects on cell activity. CONCLUSIONS: Our data indicated that the circRNA has_circ_0045881 plays key roles in TNBC progression and that hsa_circ_0045881 might act as a sponge for miR-214-3p to modulate its levels in TNBC cells, thereby regulating cell invasion, metastasis and proliferation. hsa_circ_004588 might be a potential prognostic marker and therapeutic target for TNBC.
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MicroARNs , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/genética , ARN Circular/genética , MicroARNs/genética , Proliferación Celular/genética , Vendajes , Línea Celular TumoralRESUMEN
In this study, a new biomaterial with polyvinyl alcohol (PVA)/sodium caseinate (SodCa)/reduced graphene oxide (rGO) structure was developed. Antibacterial effective nanofibers were successfully produced by electrospinning method from 1%, 3%, 5%, and 7% rGO added PVA/SodCa (60:40, w:w) solution mixtures prepared for use as modern wound dressings. To create a usage area, especially in exuding wounds, hydrophilic PVA/SodCa/rGO electrospun mats were cross-linked by dipping them in a glutaraldehyde (GLA) bath. The surface micrographs of all nanofibers were homogeneous and smooth. rGO-doped biomaterials were obtained as thin nanofibers in the range of 301-348 nm. Nanofibers, which were completely soluble in water, after cross-linking preserved their existence in the range of 87%-81% at the end of the 24th hour in distilled water. It was reported that these biomaterials that persist in an aqueous environment show swelling behavior in the range of 275%-608%. The porosity of uncross-linked pure PVA/SodCa nanofibers increased by 46.75% after cross-linking. Moreover, the tensile strength of cross-linked PVA/SodCa electrospun mats increased in the presence of rGO. Provided that wound dressing is done every 24 h with 3% rGO-doped PVA/SodCa nanofiber and provided that wound dressing is done every 48 h with 5% rGO-doped PVA/SodCa nanofiber showed antibacterial activity against S. aureus as 99.38% and 99.55%, respectively.