RESUMEN
BACKGROUND: Key wound environment parameters include pH, hydration, and the balance between tissue remodeling and deposition of new tissue. When prolonged inflammation is present, the proliferation phase of wound healing can be delayed because excessive protease production due to persistent inflammation can destroy newly formed tissue and prevent wounds from filling and reepithelializing. OBJECTIVE: To conduct an in vitro study of the ability of polygalacturonic acid (PG), a natural pectin derivative present in ripening fruit, to inhibit 3 destructive wound proteases and prevent dehydration in environments in which significant evaporation can occur. MATERIALS AND METHODS: In vitro enzyme inhibition assay kits were used to detect the ability of PG to inhibit key wound proteases matrix metalloproteinase (MMP)-2, MMP-9, and neutrophil elastase (NE). Transepidermal evaporative water loss from a polyvinyl alcohol skin substitute hydrogel was gravimetrically measured. RESULTS: PG could partially inhibit MMP-2 (>50% inhibition relative to negative controls), MMP-9 (>50% inhibition relative to negative controls), and NE (>25% inhibition relative to negative controls) and thereby potentially blunt some of the destructive effects of excess proteases where prolonged inflammation is present. In an in vitro transepidermal evaporative water loss assay, PG also helped retain moisture and inhibited dehydration (>25% reduction relative to negative controls). CONCLUSIONS: These findings suggest that PG can be a useful addition to ointments and dressings in wound care and warrants further in vivo testing.
Asunto(s)
Deshidratación , Metaloproteinasa 2 de la Matriz , Metaloproteinasa 9 de la Matriz , Pectinas , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Pectinas/farmacología , Humanos , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Elastasa de Leucocito/metabolismo , Elastasa de Leucocito/antagonistas & inhibidores , Heridas y Lesiones/patología , Pérdida Insensible de Agua/efectos de los fármacosRESUMEN
BACKGROUND: Wound healing involves the repair of skin and other soft tissues after an injury. Royal jelly, a product of bees, possesses antioxidant, anti-inflammatory, antibacterial, and antiviral properties. Melatonin, a circadian indoleamine, is produced in the pineal gland and other organs. This study explores the effects of melatonin and royal jelly, both individually and combined, on wound healing in geriatric and young mice. METHODS: The study includes 90 Balb/C mice divided into ten groups to assess the effects of royal jelly and melatonin on wound healing. Royal jelly was applied topically at a concentration of 300 mg/kg. Melatonin was formulated in a vaseline-based pomade at a concentration of 5 mg/kg. The substances were applied either separately or in combination to wounds created on the mice. RESULTS: Both substances significantly enhanced wound healing at a macroscopic level in both age groups. Melatonin was found to be more effective during the initial wound formation process, whereas royal jelly was more beneficial during the granulation phase. However, significant results at a histopathological level were observed only in geriatric animals. CONCLUSION: The findings suggest a potential new therapeutic approach to enhance wound healing, particularly in elderly individuals. However, these findings need to be supported through further research and clinical trials.
Asunto(s)
Ácidos Grasos , Melatonina , Ratones Endogámicos BALB C , Cicatrización de Heridas , Animales , Melatonina/farmacología , Melatonina/administración & dosificación , Melatonina/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos , Ratones , Ácidos Grasos/administración & dosificación , Masculino , Modelos Animales de Enfermedad , Antioxidantes/farmacología , Antioxidantes/administración & dosificación , Heridas y Lesiones/tratamiento farmacológico , Heridas y Lesiones/patologíaRESUMEN
BACKGROUND: Patients with hemorrhagic shock and trauma (HS/T) are vulnerable to the endotheliopathy of trauma (EOT), characterized by vascular barrier dysfunction, inflammation, and coagulopathy. Cellular therapies such as mesenchymal stem cells (MSCs) and MSC extracellular vesicles (EVs) have been proposed as potential therapies targeting the EOT. In this study we investigated the effects of MSCs and MSC EVs on endothelial and epithelial barrier integrity in vitro and in vivo in a mouse model of HS/T. This study addresses the systemic effects of HS/T on multiorgan EOT. METHODS: In vitro, pulmonary endothelial cell (PEC) and Caco-2 intestinal epithelial cell monolayers were treated with control media, MSC conditioned media (CM), or MSC EVs in varying doses and subjected to a thrombin or hydrogen peroxide (H2O2) challenge, respectively. Monolayer permeability was evaluated with a cell impedance assay, and intercellular junction integrity was evaluated with immunofluorescent staining. In vivo, a mouse model of HS/T was used to evaluate the effects of lactated Ringer's (LR), MSCs, and MSC EVs on endothelial and epithelial intercellular junctions in the lung and small intestine as well as on plasma inflammatory biomarkers. RESULTS: MSC EVs and MSC CM attenuated permeability and preserved intercellular junctions of the PEC monolayer in vitro, whereas only MSC CM was protective of the Caco-2 epithelial monolayer. In vivo, both MSC EVs and MSCs mitigated the loss of endothelial adherens junctions in the lung and small intestine, though only MSCs had a protective effect on epithelial tight junctions in the lung. Several plasma biomarkers including MMP8 and VEGF were elevated in LR- and EV-treated but not MSC-treated mice. CONCLUSIONS: In conclusion, MSC EVs could be a potential cell-free therapy targeting endotheliopathy after HS/T via preservation of the vascular endothelial barrier in multiple organs early after injury. Further research is needed to better understand the immunomodulatory effects of these products following HS/T and to move toward translating these therapies into clinical studies.
Asunto(s)
Vesículas Extracelulares , Células Madre Mesenquimatosas , Ratones Endogámicos C57BL , Choque Hemorrágico , Vesículas Extracelulares/metabolismo , Animales , Choque Hemorrágico/metabolismo , Humanos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Células CACO-2 , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Masculino , Heridas y Lesiones/patología , Medios de Cultivo Condicionados/farmacología , Ratones , Células Endoteliales/metabolismo , Pulmón/patología , Peróxido de Hidrógeno/metabolismo , Uniones Intercelulares/metabolismoRESUMEN
The increasing global prevalence of chronic wounds underscores the growing importance of developing effective animal models for their study. This review offers a critical evaluation of the strengths and limitations of rat models frequently employed in chronic wound research and proposes potential improvements. It explores these models in the context of key comorbidities, including diabetes, venous and arterial insufficiency, pressure-induced blood flow obstruction, and infections. Additionally, the review examines important wound factors including age, sex, smoking, and the impact of anesthetic and analgesic drugs, acknowledging their substantial effects on research outcomes. A thorough understanding of these variables is crucial for refining animal models and can provide valuable insights for future research endeavors.
Asunto(s)
Modelos Animales de Enfermedad , Cicatrización de Heridas , Animales , Ratas , Cicatrización de Heridas/fisiología , Enfermedad Crónica , Heridas y Lesiones/patología , HumanosRESUMEN
Heterotopic ossification is the inappropriate formation of bone in soft tissues of the body. It can manifest spontaneously in rare genetic conditions or as a response to injury, known as acquired heterotopic ossification. There are several experimental models for studying acquired heterotopic ossification from different sources of damage. However, their tenuous mechanistic relevance to the human condition, invasive and laborious nature and/or lack of amenability to chemical and genetic screens, limit their utility. To address these limitations, we developed a simple zebrafish injury model that manifests heterotopic ossification with high penetrance in response to clinically emulating injuries, as observed in human myositis ossificans traumatica. Using this model, we defined the transcriptional response to trauma, identifying differentially regulated genes. Mutant analyses revealed that an increase in the activity of the potassium channel Kcnk5b potentiates injury response, whereas loss of function of the interleukin 11 receptor paralogue (Il11ra) resulted in a drastically reduced ossification response. Based on these findings, we postulate that enhanced ionic signalling, specifically through Kcnk5b, regulates the intensity of the skeletogenic injury response, which, in part, requires immune response regulated by Il11ra.
Asunto(s)
Osificación Heterotópica , Proteínas de Pez Cebra , Pez Cebra , Animales , Pez Cebra/genética , Osificación Heterotópica/genética , Osificación Heterotópica/patología , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Regulación de la Expresión Génica , Envejecimiento/genética , Envejecimiento/patología , Heridas y Lesiones/complicaciones , Heridas y Lesiones/genética , Heridas y Lesiones/patología , Modelos Animales de Enfermedad , Mutación/genéticaRESUMEN
Despite advances in the treatment and care of severe physical injuries, trauma remains one of the main reasons for disability-adjusted life years worldwide. Trauma patients often suffer from disturbances in energy utilization and metabolic dysfunction, including hyperglycemia and increased insulin resistance. White adipose tissue plays an essential role in the regulation of energy homeostasis and is frequently implicated in traumatic injury due to its ubiquitous body distribution but remains poorly studied. Initial triggers of the trauma response are mainly damage-associated molecular patterns (DAMPs) such as histones. We hypothesized that DAMP-induced adipose tissue inflammation contributes to metabolic dysfunction in trauma patients. Therefore, we investigated whether histone release during traumatic injury affects adipose tissue. Making use of a murine polytrauma model with hemorrhagic shock, we found increased serum levels of histones accompanied by an inflammatory response in white adipose tissue. In vitro, extracellular histones induced an inflammatory response in human adipocytes. On the molecular level, this inflammatory response was mediated via a MYD88-IRAK1-ERK signaling axis as demonstrated by pharmacological and genetic inhibition. Histones also induced lytic cell death executed independently of caspases and RIPK1 activity. Importantly, we detected increased histone levels in the bloodstream of patients after polytrauma. Such patients might benefit from a therapy consisting of activated protein C and the FDA-approved ERK inhibitor trametinib, as this combination effectively prevented histone-mediated effects on both, inflammatory gene activation and cell death in adipocytes. Preventing adipose tissue inflammation and adipocyte death in patients with polytrauma could help minimize posttraumatic metabolic dysfunction.
Asunto(s)
Adipocitos , Histonas , Inflamación , Factor 88 de Diferenciación Mieloide , Humanos , Animales , Histonas/metabolismo , Adipocitos/metabolismo , Adipocitos/efectos de los fármacos , Inflamación/patología , Inflamación/metabolismo , Ratones , Factor 88 de Diferenciación Mieloide/metabolismo , Muerte Celular/efectos de los fármacos , Masculino , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones Endogámicos C57BL , Heridas y Lesiones/complicaciones , Heridas y Lesiones/metabolismo , Heridas y Lesiones/patología , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVE: A comparison between Cinematic Rendering Technique (CRT) and Volume Rendering Technique (VRT) in cases with postmortem CT-angiography (PMCTA) was carried out. METHODS: For different injuries seen in PMCTA, a VRT and a CRT image of exactly the same pathological section was generated. Two questionnaires were created, one with CRT and one with VRT reconstructions, with the same questions per 3D-image. The questionnaires were sent to forensic pathologists, lawyers and police officers. In total eleven different injuries had to be analyzed. RESULTS: In total 109 questionnaires were answered fully. Of these returnees, 36 stated that they were forensic pathologists. Seventy-three people were assigned to the group of medical laypersons, in the study this group consists mainly of police officers, judges and lawyers. Between the two software programs CRT and VRT that were compared, no significant difference could be identified in any of the participating groups with regard to the assessment of the life-threatening nature of the injury images shown. When asked about the comprehensibility of pathology, there was a significant difference in favour of CRT. This advantage was apparent to named medical laypersons and to forensic pathologists. CONCLUSIONS: The study showed a positive trend that CRT may be more understandable than VRT. Not only the medical laypersons, but also the forensic physicians found CRT to be beneficial.
Asunto(s)
Medicina Legal , Imagenología Tridimensional , Humanos , Encuestas y Cuestionarios , Medicina Legal/métodos , Angiografía por Tomografía Computarizada , Policia , Abogados , Programas Informáticos , Masculino , Heridas y Lesiones/diagnóstico por imagen , Heridas y Lesiones/patologíaRESUMEN
In an aging society with common lifestyle-associated health issues such as obesity and diabetes, chronic wounds pose a frequent challenge that physicians face in everyday clinical practice. Therefore, nonhealing wounds have attracted much scientific attention. Several in vitro and in vivo models have been introduced to deepen our understanding of chronic wound pathogenesis and amplify therapeutic strategies. Understanding how wounds become chronic will provide insights to reverse or avoid chronicity. Although choosing a suitable model is of utmost importance to receive valuable outcomes, an ideal in vivo model capturing the complexity of chronic wounds is still missing and remains a translational challenge. This review discusses the most relevant mammalian models for wound healing studies and provides guidance on how to implement the hallmarks of chronic wounds. It highlights the benefits and pitfalls of established models and maps out future avenues for research.
Asunto(s)
Modelos Animales de Enfermedad , Cicatrización de Heridas , Cicatrización de Heridas/fisiología , Humanos , Animales , Enfermedad Crónica , Investigación Biomédica Traslacional , Heridas y Lesiones/patología , Piel/patología , Piel/lesionesRESUMEN
Wound closure is a fundamental process in many physiological and pathological processes, but the regulating effects of external force on the closure process are still unclear. Here, we systematically studied the closure process of wounds of different shape under cyclic stretching. We found that the stretching amplitude and direction had significant effect on the healing speed and healing mode. For instance, there was a biphasic dependence of the healing speed on the stretching amplitude. That is, the wound closure was faster under relatively small and large amplitude, while it was slower under intermediate amplitude. At the same time, the stretching could regulate the healing pattern. We showed that the stretching would increase the healing speed along the direction perpendicular to the stretching direction. Specifically, when the stretching was along the major axis of the wound, it accelerated the healing speed along the short axis, which induced a rosette to stitching-line mode transition. In contrast, stretching along the minor axis accelerated the healing speed along the long axis, inducing a stitching-line to rosette mode transition. Our theoretical analyses demonstrated that the wound closure process was coregulated by the mechanical factors including prestress in the cytoskeleton, the protrusion of cells, and the contraction of the actin ring, as well as the geometry of the wound. The cyclic stretch could further modulate the roles of these factors. For example, the stretching changed the stress field in the cell layer, and switched the direction of cell protrusions. This article reveals important cellular mechanisms of the wound healing process under cyclic stretching, and provides an insight into possible approaches of regulating cell collective behaviors via mechanical forces.
Asunto(s)
Cicatrización de Heridas , Células de Riñón Canino Madin Darby , Animales , Perros , Fenómenos Biomecánicos , Heridas y Lesiones/patología , Tiempo , Polaridad Celular , Resistencia a la TracciónRESUMEN
BACKGROUND Wound healing is a dynamic and complex process that is regulated by a variety of factors and pathways. This study sought to identify the mechanisms of the four-herb Chinese medicine ANBP in enhancing wound repair. MATERIAL AND METHODS By comparing the group treated with ANBP for 6 h (Z6h) with the corresponding control group (C6h), we used the new high-throughput differential acetylation proteomics method to explore the mechanism of ANBP treatment and analyse and identify new targets of ANBP for promoting wound healing. RESULTS ANBP promoted skin wound healing in mice; the wound healing process was accelerated and the wound healing time was shortened (P<0.05). The upregulated proteins were distributed mostly in the mitochondria to nuclear respiratory chain complexes and cytoplasmic vesicles. The dominant pathways for upregulated proteins were fatty acid metabolism, pyruvate metabolism, and tricarboxylic acid cycle. Pdha1 was upregulated with the most acetylation sites, while the downregulated Ncl, and Pfkm were most acetylated. CONCLUSIONS The findings from our study showed that ANBP improved cell aerobic respiration through enhanced glycolysis, pyruvic acid oxidative decarboxylation, and the Krebs cycle to produce more ATP for energy consumption, thus accelerating wound repair of skin.
Asunto(s)
Citocinas/metabolismo , Medicina Tradicional China/métodos , Mitocondrias/metabolismo , Proteómica/métodos , Piel/lesiones , Cicatrización de Heridas , Heridas y Lesiones/metabolismo , Acetilación , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Mitocondrias/patología , Transducción de Señal , Piel/metabolismo , Piel/patología , Regulación hacia Arriba , Heridas y Lesiones/patologíaRESUMEN
To undertake a reliable analysis of injury severity in road traffic accidents, a complete understanding of important attributes is essential. As a result of the shift from traditional statistical parametric procedures to computer-aided methods, machine learning approaches have become an important aspect in predicting the severity of road traffic injuries. The paper presents a hybrid feature selection-based machine learning classification approach for detecting significant attributes and predicting injury severity in single and multiple-vehicle accidents. To begin, we employed a Random Forests (RF) classifier in conjunction with an intrinsic wrapper-based feature selection approach called the Boruta Algorithm (BA) to find the relevant important attributes that determine injury severity. The influential attributes were then fed into a set of four classifiers to accurately predict injury severity (Naive Bayes (NB), K-Nearest Neighbor (K-NN), Binary Logistic Regression (BLR), and Extreme Gradient Boosting (XGBoost)). According to BA's experimental investigation, the vehicle type was the most influential factor, followed by the month of the year, the driver's age, and the alignment of the road segment. The driver's gender, the presence of a median, and the presence of a shoulder were all found to be unimportant. According to classifier performance measures, XGBoost surpasses the other classifiers in terms of prediction performance. Using the specified attributes, the accuracy, Cohen's Kappa, F1-Measure, and AUC-ROC values of the XGBoost were 82.10%, 0.607, 0.776, and 0.880 for single vehicle accidents and 79.52%, 0.569, 0.752, and 0.86 for multiple-vehicle accidents, respectively.
Asunto(s)
Accidentes de Tránsito/clasificación , Aprendizaje Automático , Heridas y Lesiones/patología , Área Bajo la Curva , Teorema de Bayes , Humanos , Modelos Logísticos , Pakistán , Curva ROC , Índice de Severidad de la EnfermedadRESUMEN
Skin substitutes can provide a temporary or permanent treatment option for chronic wounds. The selection of skin substitutes depends on several factors, including the type of wound and its severity. Full-thickness skin grafts (SGs) require a well-vascularised bed and sometimes will lead to contraction and scarring formation. Besides, donor sites for full-thickness skin grafts are very limited if the wound area is big, and it has been proven to have the lowest survival rate compared to thick- and thin-split thickness. Tissue engineering technology has introduced new advanced strategies since the last decades to fabricate the composite scaffold via the 3D-bioprinting approach as a tissue replacement strategy. Considering the current global donor shortage for autologous split-thickness skin graft (ASSG), skin 3D-bioprinting has emerged as a potential alternative to replace the ASSG treatment. The three-dimensional (3D)-bioprinting technique yields scaffold fabrication with the combination of biomaterials and cells to form bioinks. Thus, the essential key factor for success in 3D-bioprinting is selecting and developing suitable bioinks to maintain the mechanisms of cellular activity. This crucial stage is vital to mimic the native extracellular matrix (ECM) for the sustainability of cell viability before tissue regeneration. This comprehensive review outlined the application of the 3D-bioprinting technique to develop skin tissue regeneration. The cell viability of human skin cells, dermal fibroblasts (DFs), and keratinocytes (KCs) during in vitro testing has been further discussed prior to in vivo application. It is essential to ensure the printed tissue/organ constantly allows cellular activities, including cell proliferation rate and migration capacity. Therefore, 3D-bioprinting plays a vital role in developing a complex skin tissue structure for tissue replacement approach in future precision medicine.
Asunto(s)
Bioimpresión , Comunicación Celular , Tinta , Impresión Tridimensional , Piel/patología , Heridas y Lesiones/patología , Animales , Enfermedad Crónica , HumanosRESUMEN
The refractory diabetic wound has remained a worldwide challenge as one of the major health problems. The impaired angiogenesis phase during diabetic wound healing partly contributes to the pathological process. MicroRNA (miRNA) is an essential regulator of gene expression in crucial biological processes and is a promising nucleic acid drug in therapeutic fields of the diabetic wound. However, miRNA therapies have limitations due to lacking an effective delivery system. In the present study, we found a significant reduction of miR-31-5p expression in the full-thickness wounds of diabetic mice compared to normal mice. Further, miR-31-5p has been proven to promote the proliferation, migration, and angiogenesis of endothelial cells. Thus, we conceived the idea of exogenously supplementing miR-31-5p mimics to treat the diabetic wound. We used milk-derived exosomes as a novel system for miR-31-5p delivery and successfully encapsulated miR-31-5p mimics into milk exosomes through electroporation. Then, we proved that the miR-31-5p loaded in exosomes achieved higher cell uptake and was able to resist degradation. Moreover, our miRNA-exosomal formulation demonstrated dramatically improved endothelial cell functions in vitro, together with the promotion of angiogenesis and enhanced diabetic wound healing in vivo. Collectively, our data showed the feasibility of milk exosomes as a scalable, biocompatible, and cost-effective delivery system to enhance the bioavailability and efficacy of miRNAs.
Asunto(s)
Exosomas/metabolismo , MicroARNs/farmacología , Leche , Neovascularización Fisiológica/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Heridas y Lesiones/patología , Animales , Diabetes Mellitus Experimental/complicaciones , Portadores de Fármacos/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , MicroARNs/administración & dosificación , Heridas y Lesiones/etiologíaRESUMEN
Vehicle-tree collisions are the most common type of road crash with fixed obstacle in Czech Republic. Based on the literature review and using real world in-depth crash data, this paper aims to define factors, which significantly influence the injury severity of single vehicle-tree crashes. In-depth data provide a comprehensive view to the failure on the system infrastructure-human-vehicle related to crash, the in-depth crash database include very detailed information related to infrastructure, vehicle, human failure and crash participants characteristics and their medical condition and also crash reconstruction. Multinomial logistic regression and generalized linear mixed model were used to determine the individual effect of each predictor. The statistically significant variables were the day period, trunk diameter and impact speed. Using multinomial logistic regression shows also vehicle age as statistically significant. Obtained results can help to efficiently direct countermeasures not only on the road infrastructure-e.g. speed reduction in selected locations with specified tree character. However, the emphasis should be also focused on driver behaviour.
Asunto(s)
Accidentes de Tránsito , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , República Checa , Bases de Datos Factuales , Femenino , Humanos , Modelos Lineales , Modelos Logísticos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Índice de Severidad de la Enfermedad , Árboles , Heridas y Lesiones/etiología , Heridas y Lesiones/patología , Adulto JovenRESUMEN
With the worldwide prevalence of diabetes and considering the complicated microenvironment of diabetic wounds, the design and development of innovative multifunctional wound dressing materials are much wanted for the treatment of hard-to-heal wounds in diabetic patients. In the present study, anti-inflammatory ingredients loaded with nanofibrous wound dressing materials were manufactured by a promising blend-electrospinning strategy, and their capability for treating the diabetic wound was also systematically explored. A polymer blend consisting of Chitosan (CS) and polyvinyl alcohol (PVA) was electrospun into CS-PVA nanofibrous mats as control groups. In the meanwhile, a bioactive ingredient of Chinese medicine Pulsatilla, anemoside B4(ANE), with different contents were loaded into the electrospinning solution to construct CS-PVA-ANE nanofibrous mats. The developed CS-PVA-ANE wound dressing materials exhibited multifunctional properties including prominent water absorption, biomimetic elastic mechanical properties, and sustained ANE releasing behavior, as well as outstanding hemostatic properties. The in vitro studies showed that the CS-PVA-ANE nanofiber mats could significantly suppress lipopolysaccharide (LPS)-stimulated differentiation of pro-inflammatory (M1) macrophage subsets, and notably reduce the reactive oxygen species (ROS) generation, as well as obviously decrease inflammatory cytokine release. The in vivo animal studies showed that the CS-PVA-ANE nanofiber mats promoted the healing of diabetic wounds by significantly enhancing wound closure rates, accelerating excellent angiogenesis, promoting re-epithelization and collagen matrix deposition throughout all stages of wound healing. The present study demonstrated that CS-PVA-ANE nanofiber mats could effectively shorten the wound-healing time by inhibiting inflammatory activity, which makes them promising candidates for the treatment of hard-to-heal wounds caused by diabetes.
Asunto(s)
Nanofibras/química , Saponinas/farmacología , Cicatrización de Heridas/efectos de los fármacos , Heridas y Lesiones/patología , Animales , Biomimética , Supervivencia Celular/efectos de los fármacos , Quitosano/química , Diabetes Mellitus Experimental/complicaciones , Relación Dosis-Respuesta a Droga , Liberación de Fármacos , Mediadores de Inflamación/metabolismo , Macrófagos/efectos de los fármacos , Ratones , Alcohol Polivinílico/química , Células RAW 264.7 , Saponinas/administración & dosificación , Heridas y Lesiones/etiologíaRESUMEN
To explore the regulation of keratinocyte growth factor (KGF) in the process of repairing rat skin wounds by taspine hydrochloride (TA/HCl), 45 male Sprague-Dawley (SD) rats were purchased and divided into an experimental group, a dimethyl sulfoxide (DMSO) control group, and a basic fibroblast growth factor (bFGF) control group, each with 15 only. A back trauma model was innovatively adopted to prevent rats from biting and contaminating. The wound healing time and healing rate of the rat, and the Hydroxyproline (Hyp) and KGF expressions were observed. Morphological changes of wound tissue and the number of capillaries were observed after hematoxylin-eosin (HE) staining. The results showed that wound healing rate of experimental group and bFGF group was significantly higher than that of DMSO group (P < 0.05) after 2-15 days, and wound healing time of experimental group was 18 days, which was significantly lower than that of the DMSO group (P < 0.05). Expression levels of Hyp and KGF in the granulation tissue of rats in the experimental group were much higher than those in the DMSO control group after trauma (P < 0.05). In early stage of wound tissue repair, the number of new capillaries formed in experimental group was significantly higher than that in DMSO control group (P < 0.05). In summary, this study innovatively focused on KGF. The mechanism of TA/HCL promoting rat skin wound healing was closely related to KGF.
Asunto(s)
Alcaloides/farmacología , Factor 7 de Crecimiento de Fibroblastos/metabolismo , Transducción de Señal/efectos de los fármacos , Piel , Cicatrización de Heridas/efectos de los fármacos , Heridas y Lesiones , Animales , Masculino , Ratas , Ratas Sprague-Dawley , Piel/lesiones , Piel/metabolismo , Piel/patología , Heridas y Lesiones/tratamiento farmacológico , Heridas y Lesiones/metabolismo , Heridas y Lesiones/patologíaRESUMEN
Traumatic injury is a major cause of morbidity and mortality worldwide, despite significant advances in treatments. Most deaths occur either very early, through massive head trauma/CNS injury or exsanguination (despite advances in transfusion medicine), or later after injury often through multiple organ failure and secondary infection. Extracellular vesicles (EVs) are known to increase in the circulation after trauma and have been used to limited extent as diagnostic and prognostic markers. More intriguingly, EVs are now being investigated as both causes of pathologies post trauma, such as trauma-induced coagulopathy, and as potential treatments. In this review, we highlight what is currently known about the role and effects of EVs in various aspects of trauma, as well as exploring current literature from investigators who have begun to use EVs therapeutically to alter the physiology and pathology of traumatic insults. The potential effectiveness of using EVs therapeutically in trauma is supported by a large number of experimental studies, but there is still some way to go before we understand the complex effects of EVs in what is already a complex disease process.
Asunto(s)
Vesículas Extracelulares , Heridas y Lesiones , Animales , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patología , Vesículas Extracelulares/trasplante , Hemostasis , Humanos , Inflamación/metabolismo , Inflamación/patología , Inflamación/terapia , Trombosis/metabolismo , Trombosis/patología , Trombosis/terapia , Heridas y Lesiones/metabolismo , Heridas y Lesiones/patología , Heridas y Lesiones/terapiaRESUMEN
Injury to the optic nerve, termed, traumatic optic neuropathy (TON) is a known comorbidity of traumatic brain injury (TBI) and is now known to cause chronic and progressive retinal thinning up to 35 years after injury. Although animal models of TBI have described the presence of optic nerve degeneration and research exploring acute mechanisms is underway, few studies in humans or animals have examined chronic TON pathophysiology outside the retina. We used a closed-head weight-drop model of TBI/TON in 6-week-old male C57BL/6 mice. Mice were euthanized 7-, 14-, 30-, 90-, and 150-days post-injury (DPI) to assess histological changes in the visual system of the brain spanning a total of 12 regions. We show chronic elevation of FluoroJade-C, indicative of neurodegeneration, throughout the time course. Intriguingly, FJ-C staining revealed a bimodal distribution of mice indicating the possibility of subpopulations that may be more or less susceptible to injury outcomes. Additionally, we show that microglia and astrocytes react to optic nerve damage in both temporally and regionally different ways. Despite these differences, astrogliosis and microglial changes were alleviated between 14-30 DPI in all regions examined, perhaps indicating a potentially critical period for intervention/recovery that may determine chronic outcomes.
Asunto(s)
Envejecimiento/patología , Degeneración Nerviosa/patología , Neuroglía/patología , Traumatismos del Nervio Óptico/patología , Heridas y Lesiones/patología , Animales , Peso Corporal , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/patología , Enfermedad Crónica , Masculino , Ratones Endogámicos C57BL , Microglía/patología , Degeneración Nerviosa/complicaciones , Nervio Óptico/patología , Traumatismos del Nervio Óptico/complicaciones , Convulsiones/complicaciones , Factores de Tiempo , Heridas y Lesiones/complicacionesRESUMEN
Limb wounds are common in horses and often develop complications. Intravenous multipotent mesenchymal stromal cell (MSC) therapy is promising but has risks associated with intravenous administration and unknown potential to improve cutaneous wound healing. The objectives were to determine the clinical safety of administering large numbers of allogeneic cord blood-derived MSCs intravenously, and if therapy causes clinically adverse reactions, accelerates wound closure, improves histologic healing, and alters mRNA expression of common wound cytokines. Wounds were created on the metacarpus of 12 horses. Treatment horses were administered 1.51-2.46 × 108 cells suspended in 50% HypoThermosol FRS, and control horses were administered 50% HypoThermosol FRS alone. Epithelialization, contraction, and wound closure rates were determined using planimetric analysis. Wounds were biopsied and evaluated for histologic healing characteristics and cytokine mRNA expression. Days until wound closure was also determined. The results indicate that 3/6 of treatment horses and 1/6 of control horses experienced minor transient reactions. Treatment did not accelerate wound closure or improve histologic healing. Treatment decreased wound size and decreased all measured cytokines except transforming growth factor-ß3. MSC intravenous therapy has the potential to decrease limb wound size; however, further work is needed to understand the clinical relevance of adverse reactions.