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1.
Mol Med Rep ; 23(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33760179

RESUMO

Burn wounds present an evolutionary progression, in which the initial wound tissue deepens and expands following thermal injury. Progressive tissue damage in the zone of stasis may worsen burn injury, which is associated with oxidative stress and secondary apoptosis, and worsen the prognosis of patients with burn wounds. The mitochondrial apoptotic pathway is involved in receiving oxidative signals and regulating tissue apoptosis. Previously, Abnormal Savda Munziq (ASMq), a natural compound of traditional Uyghur Medicine, which includes ten types of herb, has been reported to exhibit a number of effects, including anti­inflammatory, antioxidative and anti­apoptotic activities. The present study demonstrated that ASMq protected against early burn wound progression following thermal injury in rats; this effect may be mediated by its ability to attenuate oxidative stress­induced mitochondria­associated apoptosis. The present study may provide a novel therapeutic method to prevent early burn wound progression following burn injury.


Assuntos
Queimaduras/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Ferimentos e Lesões/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Queimaduras/genética , Queimaduras/patologia , Modelos Animais de Doenças , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Medicina Tradicional/métodos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ratos , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/genética , Ferimentos e Lesões/patologia , Proteína de Morte Celular Associada a bcl/genética
2.
Int J Mol Sci ; 22(4)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33557424

RESUMO

Thermal injuries are caused by exposure to a variety of sources, and split thickness skin grafts are the gold standard treatment for severe burns; however, they may be impossible when there is no donor skin available. Large total body surface area burns leave patients with limited donor site availability and create a need for treatments capable of achieving early and complete coverage that can also retain normal skin function. In this preclinical trial, two cellular and tissue based products (CTPs) are evaluated on twenty-four 5 × 5 deep partial thickness (DPT) burn wounds. Using appropriate pain control methods, DPT burn wounds were created on six anesthetized Yorkshire pigs. Wounds were excised one day post-burn and the bleeding wound beds were subsequently treated with omega-3-rich acellular fish skin graft (FSG) or fetal bovine dermis (FBD). FSG was reapplied after 7 days and wounds healed via secondary intentions. Digital images, non-invasive measurements, and punch biopsies were acquired during rechecks performed on days 7, 14, 21, 28, 45, and 60. Multiple qualitative measurements were also employed, including re-epithelialization, contraction rates, hydration, laser speckle, and trans-epidermal water loss (TEWL). Each treatment produced granulated tissue (GT) that would be receptive to skin grafts, if desired; however, the FSG induced GT 7 days earlier. FSG treatment resulted in faster re-epithelialization and reduced wound size at day 14 compared to FBD (50.2% vs. 23.5% and 93.1% vs. 106.7%, p < 0.005, respectively). No differences in TEWL measurements were observed. The FSG integrated into the wound bed quicker as evidenced by lower hydration values at day 21 (309.7 vs. 2500.4 µS, p < 0.05) and higher blood flow at day 14 (4.9 vs. 3.1 fold change increase over normal skin, p < 0.005). Here we show that FSG integrated faster without increased contraction, resulting in quicker wound closure without skin graft application which suggests FSG improved burn wound healing over FBD.


Assuntos
Derme Acelular/provisão & distribução , Queimaduras/cirurgia , Transplante de Pele/métodos , Cicatrização , Animais , Queimaduras/patologia , Feminino , Peixes , Suínos
3.
Int J Nanomedicine ; 16: 833-850, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33584096

RESUMO

Purpose: In deep burns, wound contraction and hypertrophic scar formation can generate functional derangement and debilitation of the affected part. In order to improve the quality of healing in deep second-degree burns, we developed a new treatment in a preclinical model using nanostructured membranes seeded with mesenchymal stem cells (MSCs). Methods: Membranes were obtained by reconstitution of bacterial cellulose (reconstituted membrane [RM]) and produced by a dry-cast process, then RM was incorporated with 10% tamarind xyloglucan plus gellan gum 1:1 and 10% lysozyme (RMGT-LZ) and with 10% gellan gum and 10% lysozyme (RMG-LZ). Membrane hydrophobic/hydrophilic characteristics were investigated by static/dynamic contact-angle measurements. They were cultivated with MSCs, and cell adhesion, proliferation, and migration capacity was analyzed with MTT assays. Morphological and topographic characteristics were analyzed by scanning electron microscopy. MSC patterns in flow cytometry and differentiation into adipocytes and osteocytes were checked. In vivo assays used RMG-LZ and RMGT-LZ (with and without MSCs) in Rattus norvegicus rats submitted to burn protocol, and histological sections and collagen deposits were analyzed and immunocytochemistry assay performed. Results: In vitro results demonstrated carboxyl and amine groups made the membranes moderately hydrophobic and xyloglucan inclusion decreased wettability, favoring MSC adhesion, proliferation, and differentiation. In vivo, we obtained 40% and 60% reduction in acute/chronic inflammatory infiltrates, 96% decrease in injury area, increased vascular proliferation and collagen deposition, and complete epithelialization after 30 days. MSCs were detected in burned tissue, confirming they had homed and proliferated in vivo. Conclusion: Nanostructured cellulose-gellan-xyloglucan-lysozyme dressings, especially when seeded with MSCs, improved deep second-degree burn regeneration.


Assuntos
Bandagens , Queimaduras/terapia , Celulose/química , Glucanos/química , Células-Tronco Mesenquimais/citologia , Muramidase/química , Nanoestruturas/química , Polissacarídeos Bacterianos/química , Xilanos/química , Animais , Vasos Sanguíneos/patologia , Queimaduras/patologia , Adesão Celular , Diferenciação Celular , Proliferação de Células , Celulose/ultraestrutura , Colágeno/metabolismo , Inflamação/patologia , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/ultraestrutura , Nanoestruturas/ultraestrutura , Ratos Wistar , Cicatrização
4.
Life Sci ; 276: 119095, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33493522

RESUMO

AIMS: Deep burn-wounds undergo a dynamic progression in the initial or periburn area after insults, and the zone of stasis is the crucial region suffering the deterioration, considered as salvageable. Few studies explored the role of mitochondria in this process. This study is to clarify a possible "built-in" protection of mitophagy. MAIN METHODS: A classic "comb" scald rat model was established. Histological and blood-flow observation were processed based on hematoxylin-eosin staining and laser analysis. Oxidative and apoptotic status were analyzed by commercial kits. Transmission-electron microscope, immunofluorescence staining, and western blot were applied to detect the mitophagy in the zone of stasis and potential regulators. Adenovirus-based gene-silence contributed to determine the role of HIF-1α as a regulatory mediator. KEY FINDINGS: We found that burn-caused typical ischemia and histological deterioration in the zone of stasis, in parallel with increases in oxidative stress and apoptosis. Mitochondrial damage was involved in the aforementioned changes. Furthermore, we detected mitophagy in burn-wounds, which was contradictory to the burn-wound conversion. HIF-1α expression was closely related to the level of mitophagy, while BNIP3 and PARKIN are involved downstream. SIGNIFICANCE: We demonstrate that burn-induced mitochondrial impairment contributes to the mobilization of injurious mechanisms in the zone of stasis and that mitophagy provides a beneficial way to protect against burn-wound progression via the elimination of damaged mitochondria. Our findings offer insights into mitochondrial quality control in burn-wound progression and suggest the novel concept that HIF-1α may be a therapeutic target due to its possible regulation on BNIP3- or PARKIN-mediated mitophagy.


Assuntos
Apoptose , Queimaduras/prevenção & controle , Mitocôndrias/patologia , Mitofagia , Estresse Oxidativo , Substâncias Protetoras , Cicatrização , Animais , Queimaduras/patologia , Masculino , Mitocôndrias/metabolismo , Ratos , Ratos Sprague-Dawley , Ubiquitina-Proteína Ligases/metabolismo
5.
J Forensic Leg Med ; 78: 102115, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33454655

RESUMO

Understanding the taphonomic process of burning allows forensic practitioners to better interpret remains and reconstruct the burning incident in a medicolegal investigation. This can yield critical information, especially when other details, such as the biological profile, are obscured by fire. A forensic case involving human remains recovered within a Greek Orthodox cemetery that exhibited a distinctive pattern of differential burning is reported. The bones exhibited a range of differential burning in a pattern inconsistent with the anatomical position of the remains during heat exposure. No macroscopic signs of skeletal trauma or evidence of dismemberment were present on the remains. The pre-burning condition of the bones was inferred based on the presence of the differential burning and its localization identified through analysis of a suite of macroscopic heat-induced traits, as well as consideration of the forensic context. The anthropologists concluded that the bones were skeletonized prior to burning and that the remains were once interred or stored in an ossuary and were likely burned in a ritualistic manner, given the artifacts present and the conspicuous location of the burn area. This case highlights the practical experience required of forensic practitioners encountering burned remains and the necessity of understanding fire as a taphonomic agent that can be analyzed to determine pre-burning condition and the scenario of the burning event in a medicolegal investigation. Furthermore, this case underscores the achievability of pre-burning condition determination using macroscopic traits alone, even when there is a paucity of skeletal elements in the inventory. Due to knowledge of the funerary customs of modern-day Greece, the practitioners were able to interpret the origin of the remains, thereby this paper provides insight into a geographically specific forensic context.


Assuntos
Restos Mortais/patologia , Osso e Ossos/lesões , Queimaduras/patologia , Fogo , Antropologia Forense/métodos , Humanos , Mudanças Depois da Morte
6.
J Zoo Wildl Med ; 51(4): 1047-1051, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33480588

RESUMO

Necropsies were performed on five eastern box turtles (Terrapene carolina carolina), found in an area recently subjected to an early-season prescribed fire, to determine whether mortality was burn related. External injuries primarily consisted of burns to exposed extremities and carapacial scutes which ranged from two burned scales to >80% of the shell. Internally, there was no evidence of smoke inhalation, but multiorgan and multifocal inflammation may have contributed to mortality.


Assuntos
Queimaduras/veterinária , Fogo , Tartarugas , Animais , Queimaduras/patologia , Feminino , Masculino
7.
J Surg Res ; 257: 56-68, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32818785

RESUMO

BACKGROUND: Burn injuries (BIs) due to scalding are one of the most common accidents among children. BIs greater than 40% of total body surface area are considered extensive and result in local and systemic response. We sought to assess morphological and myogenic mechanisms through both short- and long-term intensive insulin therapies that affect the skeletal muscle after extensive skin BI in young rats. MATERIALS AND METHODS: Wistar rats aged 21 d were distributed into four groups: control (C), control with insulin (C + I), scald burn injury (SI), and SI with insulin (SI + I). The SI groups were submitted to a 45% total body surface area burn, and the C + I and SI + I groups received insulin (5 UI/Kg/d) for 4 or 14 d. Glucose tolerance and the homeostatic model assessment of insulin resistance index were determined. Gastrocnemius muscles were analyzed for histopathological, morphometric, and immunohistochemical myogenic parameters (Pax7, MyoD, and MyoG); in addition, the expression of genes related to muscle atrophy (MuRF1 and MAFbx) and its regulation (IGF-1) were also assessed. RESULTS: Short-term treatment with insulin favored muscle regeneration by primary myogenesis and decreased muscle atrophy in animals with BIs, whereas the long-term treatment modulated myogenesis by increasing the MyoD protein. Both treatments improved histopathological parameters and secondary myogenesis by increasing the MyoG protein. CONCLUSIONS: Treatment with insulin benefits myogenic parameters during regeneration and modulates MuRF1, an important mediator of muscle atrophy.


Assuntos
Queimaduras/complicações , Insulina/administração & dosagem , Desenvolvimento Muscular/efeitos dos fármacos , Atrofia Muscular/prevenção & controle , Animais , Glicemia/análise , Superfície Corporal , Queimaduras/patologia , Queimaduras/fisiopatologia , Expressão Gênica/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/genética , Masculino , Proteínas Musculares/genética , Músculo Esquelético/química , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Atrofia Muscular/etiologia , Atrofia Muscular/genética , Proteína MyoD/análise , Miogenina/análise , Fatores de Transcrição Box Pareados/análise , Ratos , Ratos Wistar , Proteínas Ligases SKP Culina F-Box/genética , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genética
8.
Methods Mol Biol ; 2225: 93-105, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33108659

RESUMO

In vivo wound healing models are predictive preclinical tests for therapeutics that enhance skin repair or limit scarring. Large animals, such as swine, heal in a manner similar to humans, but testing is impractical and expensive. Experiments in mice are more economic, but may be less translatable as this species heals primarily through contraction, not by the processes of epithelialization and granulation tissue formation as seen in human wounds. Here, we describe a murine model of thermal burn injury that closely mimics human healing, resulting in a large, hypertrophic-like scar. This practical, reproducible model is ideal for testing promising wound-healing therapies, such as virus-derived growth factors and immune-modulatory proteins.


Assuntos
Queimaduras/patologia , Cicatriz/prevenção & controle , Modelos Animais de Doenças , Reepitelização/genética , Animais , Queimaduras/genética , Queimaduras/terapia , Cicatriz/genética , Cicatriz/patologia , Feminino , Expressão Gênica , Temperatura Alta , Humanos , Fatores Imunológicos/biossíntese , Fatores Imunológicos/genética , Fatores Imunológicos/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Reepitelização/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/lesões , Transgenes , Vírus/genética
9.
Cell Death Dis ; 11(12): 1054, 2020 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-33311441

RESUMO

Wound healing is a complex physiologic process that proceeds in overlapping, sequential steps. Plasminogen promotes fibrinolysis and potentiates the inflammatory response during wound healing. We have tested the hypothesis that the novel plasminogen receptor, Plg-RKT, regulates key steps in wound healing. Standardized burn wounds were induced in mice and time dependence of wound closure was quantified. Healing in Plg-RKT-/- mice was significantly delayed during the proliferation phase. Expression of inflammatory cytokines was dysregulated in Plg-RKT-/- wound tissue. Consistent with dysregulated cytokine expression, a significant delay in wound healing during the proliferation phase was observed in mice in which Plg-RKT was specifically deleted in myeloid cells. Following wound closure, the epidermal thickness was less in Plg-RKT-/- wound tissue. Paradoxically, deletion of Plg-RKT, specifically in keratinocytes, significantly accelerated the rate of healing during the proliferation phase. Mechanistically, only two genes were upregulated in Plg-RKT-/- compared with Plg-RKT+/+ wound tissue, filaggrin, and caspase 14. Both filaggrin and caspase 14 promote epidermal differentiation and decrease proliferation, consistent with more rapid wound closure and decreased epidermal thickness during the remodeling phase. Fibrin clearance was significantly impaired in Plg-RKT-/- wound tissue. Genetic reduction of fibrinogen levels to 50% completely abrogated the effect of Plg-RKT deletion on the healing of burn wounds. Remarkably, the effects of Plg-RKT deletion on cytokine expression were modulated by reducing fibrinogen levels. In summary, Plg-RKT is a new regulator participating in different phases of cutaneous burn wound healing, which coordinately plays a role in the interrelated responses of inflammation, keratinocyte migration, and fibrinolysis.


Assuntos
Fibrinólise , Inflamação/metabolismo , Plasminogênio/metabolismo , Receptores de Superfície Celular/metabolismo , Pele/patologia , Cicatrização , Animais , Queimaduras/genética , Queimaduras/patologia , Proliferação de Células/genética , Epiderme/patologia , Fibrinogênio/metabolismo , Fibrinólise/genética , Deleção de Genes , Regulação da Expressão Gênica , Heterozigoto , Inflamação/genética , Queratinócitos/patologia , Camundongos Endogâmicos C57BL , Receptores de Superfície Celular/deficiência , Receptores de Superfície Celular/genética , Cicatrização/genética
10.
Sci Rep ; 10(1): 21818, 2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33311597

RESUMO

Burn wounds are highly susceptible sites for colonization and infection by bacteria and fungi. Large wound surface, impaired local immunity, and broad-spectrum antibiotic therapy support growth of opportunistic fungi such as Candida albicans, which may lead to invasive candidiasis. Currently, it remains unknown whether depressed host defenses or fungal virulence drive the progression of burn wound candidiasis. Here we established an ex vivo burn wound model, where wounds were inflicted by applying preheated soldering iron to human skin explants, resulting in highly reproducible deep second-degree burn wounds. Eschar removal by debridement allowed for deeper C. albicans penetration into the burned tissue associated with prominent filamentation. Active migration of resident tissue neutrophils towards the damaged tissue and release of pro-inflammatory cytokine IL-1ß accompanied the burn. The neutrophil recruitment was further increased upon supplementation of the model with fresh immune cells. Wound area and depth decreased over time, indicating healing of the damaged tissue. Importantly, prominent neutrophil presence at the infected site correlated to the limited penetration of C. albicans into the burned tissue. Altogether, we established a reproducible burn wound model of candidiasis using ex vivo human skin explants, where immune responses actively control the progression of infection and promote tissue healing.


Assuntos
Queimaduras/imunologia , Candida albicans/imunologia , Candidíase/imunologia , Neutrófilos/imunologia , Pele/imunologia , Infecção dos Ferimentos/imunologia , Adulto , Queimaduras/microbiologia , Queimaduras/patologia , Candidíase/patologia , Feminino , Humanos , Interleucina-1beta/imunologia , Pessoa de Meia-Idade , Neutrófilos/patologia , Pele/microbiologia , Pele/patologia , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia
11.
Cochrane Database Syst Rev ; 9: CD012826, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32882071

RESUMO

BACKGROUND: Burn injuries are the fourth most common traumatic injury, causing an estimated 180,000 deaths annually worldwide. Superficial burns can be managed with dressings alone, but deeper burns or those that fail to heal promptly are usually treated surgically. Acute burns surgery aims to debride burnt skin until healthy tissue is reached, at which point skin grafts or temporising dressings are applied. Conventional debridement is performed with an angled blade, tangentially shaving burned tissue until healthy tissue is encountered. Hydrosurgery, an alternative to conventional blade debridement, simultaneously debrides, irrigates, and removes tissue with the aim of minimising damage to uninjured tissue. Despite the increasing use of hydrosurgery, its efficacy and the risk of adverse events following surgery for burns is unclear. OBJECTIVES: To assess the effects of hydrosurgical debridement and skin grafting versus conventional surgical debridement and skin grafting for the treatment of acute partial-thickness burns. SEARCH METHODS: In December 2019 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that enrolled people of any age with acute partial-thickness burn injury and assessed the use of hydrosurgery. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data extraction, 'Risk of bias' assessment, and GRADE assessment of the certainty of the evidence. MAIN RESULTS: One RCT met the inclusion criteria of this review. The study sample size was 61 paediatric participants with acute partial-thickness burns of 3% to 4% total burn surface area. Participants were randomised to hydrosurgery or conventional debridement. There may be little or no difference in mean time to complete healing (mean difference (MD) 0.00 days, 95% confidence interval (CI) -6.25 to 6.25) or postoperative infection risk (risk ratio 1.33, 95% CI 0.57 to 3.11). These results are based on very low-certainty evidence, which was downgraded twice for risk of bias, once for indirectness, and once for imprecision. There may be little or no difference in operative time between hydrosurgery and conventional debridement (MD 0.2 minutes, 95% CI -12.2 to 12.6); again, the certainty of the evidence is very low, downgraded once for risk of bias, once for indirectness, and once for imprecision. There may be little or no difference in scar outcomes at six months. Health-related quality of life, resource use, and other adverse outcomes were not reported. AUTHORS' CONCLUSIONS: This review contains one randomised trial of hydrosurgery versus conventional debridement in a paediatric population with low percentage of total body surface area burn injuries. Based on the available trial data, there may be little or no difference between hydrosurgery and conventional debridement in terms of time to complete healing, postoperative infection, operative time, and scar outcomes at six months. These results are based on very low-certainty evidence. Further research evaluating these outcomes as well as health-related quality of life, resource use, and other adverse event outcomes is required.


Assuntos
Queimaduras/cirurgia , Desbridamento/métodos , Hidroterapia/métodos , Viés , Queimaduras/patologia , Criança , Humanos , Duração da Cirurgia , Transplante de Pele , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Irrigação Terapêutica/métodos , Fatores de Tempo , Cicatrização
12.
Proc Natl Acad Sci U S A ; 117(36): 22351-22356, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32826331

RESUMO

Cytokine release syndrome (CRS) is a life-threatening complication induced by systemic inflammatory responses to infections, including bacteria and chimeric antigen receptor T cell therapy. There are currently no immunotherapies with proven clinical efficacy and understanding of the molecular mechanisms of CRS pathogenesis is limited. Here, we found that patients diagnosed with CRS from sepsis, acute respiratory distress syndrome (ARDS), or burns showed common manifestations: strikingly elevated levels of the four proinflammatory cytokines interleukin (IL)-6, IL-8, monocyte chemotactic protein-1 (MCP-1), and IL-10 and the coagulation cascade activator plasminogen activator inhibitor-1 (PAI-1). Our in vitro data indicate that endothelial IL-6 trans-signaling formed an inflammation circuit for robust IL-6, IL-8, and MCP-1 production and promoted PAI-1 production; additionally, an IL-6 signaling blockade by the human monoclonal antibody tocilizumab blunted endothelial cell activation. Plasma from severe COVID-19 patients similarly exhibited increased IL-6, IL-10, and MCP-1 levels, but these levels were not as high as those in patients with CRS from other causes. In contrast, the PAI-1 levels in COVID-19 patients were as highly elevated as those in patients with bacterial sepsis or ARDS. Tocilizumab treatment decreased the PAI-1 levels and alleviated critical illness in severe COVID-19 patients. Our findings suggest that distinct levels of cytokine production are associated with CRS induced by bacterial infection and COVID-19, but both CRS types are accompanied by endotheliopathy through IL-6 trans-signaling. Thus, the present study highlights the crucial role of IL-6 signaling in endothelial dysfunction during bacterial infection and COVID-19.


Assuntos
Síndrome da Liberação de Citocina/metabolismo , Células Endoteliais/metabolismo , Interleucina-6/metabolismo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Transdução de Sinais , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Betacoronavirus , Queimaduras/metabolismo , Queimaduras/patologia , Células Cultivadas , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/patologia , Citocinas/sangue , Citocinas/metabolismo , Células Endoteliais/efeitos dos fármacos , Feminino , Humanos , Inflamação , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Pandemias , Inibidor 1 de Ativador de Plasminogênio/sangue , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/metabolismo , Pneumonia Viral/patologia , Receptores de Interleucina-6/antagonistas & inibidores , Receptores de Interleucina-6/metabolismo , /patologia , Sepse/metabolismo , Sepse/patologia
13.
J Vis Exp ; (162)2020 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-32831317

RESUMO

Trivial superficial wounds heal without complications by primary intention. Deep wounds, such as full thickness burns, heal by secondary intention and require surgical debridement and skin grafting. Successful integration of the donor graft into a recipient wound bed depends on timely recruitment of immune cells, robust angiogenic response and new extracellular matrix formation. The development of novel therapeutic agents, which target some key processes involved in wound healing, are hindered by the lack of reliable preclinical models with optimized objective assessment of wound closure. Here, we describe an inexpensive and reproducible model of experimental full thickness burn wound reconstructed with an allogeneic skin graft. The wound is induced on the dorsum surface of anaesthetized inbred wild type mice from the BALB/C and SKH1-Hrhr backgrounds. The burn is produced using a brass template measuring 10 mm in diameter, which is preheated to 80 °C and delivered at a constant pressure for 20 s. Burn eschar is excised 24 hours after the injury and replaced with a full thickness graft harvested from the tail of a genetically similar donor mouse. No specialized equipment is required for the procedure and surgical techniques are straightforward to follow. The method may be effortlessly implemented and reproduced in most research settings. Certain limitations are associated with the model. Due to technical difficulties, the harvest of thinner split thickness skin grafts is not possible. The surgical method we describe here allows for the reconstruction of burn wounds using full thickness skin grafts. It may be used to carry out preclinical therapeutic testing.


Assuntos
Queimaduras/patologia , Modelos Animais de Doenças , Transplante de Pele , Aloenxertos , Animais , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Pele/métodos
14.
Int J Nanomedicine ; 15: 5645-5659, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32848391

RESUMO

Introduction: Mesenchymal stem cells (MSCs) are a promising resource for tissue regeneration and repair. However, their clinical application is hindered by technical limitations related to MSC enrichment at the target sites. Methods: MSCs were labeled with magnetic Fe3O4 nanoparticles (NPs). We analyzed the effects of NP on cell proliferation, stem cell characteristics, and cytokine secretion. Furthermore, we induced NP-labeled MSC migration with an external magnetic field toward laser-induced skin wounds in rats and evaluated the associated anti-inflammatory effects. Results: Fe3O4 NP application did not adversely affect MSC characteristics. Moreover, Fe3O4 NP-labeled MSCs presented increased anti-inflammatory cytokine and chemokine production compared with unlabeled MSCs. Furthermore, MSCs accumulated at the injury site and magnetic targeting promoted NP-labeled MSC migration toward burn injury sites in vivo. On day 7 following MSC injection, reduced inflammation and promoted angiogenesis were observed in the magnetically targeted MSC group. In addition, anti-inflammatory factors were upregulated, whereas pro-inflammatory factors were downregulated within the magnetically targeted MSC group compared with those in the PBS group. Conclusion: This study demonstrates that magnetically targeted MSCs contribute to cell migration to the site of skin injury, improve anti-inflammatory effects and enhance angiogenesis compared with MSC injection alone. Therefore, magnetically targeted MSC therapy may be an effective treatment approach for epithelial tissue injuries.


Assuntos
Queimaduras/terapia , Lasers/efeitos adversos , Nanopartículas de Magnetita/química , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/química , Animais , Queimaduras/etiologia , Queimaduras/patologia , Movimento Celular , Proliferação de Células , Citocinas/metabolismo , Campos Magnéticos , Nanopartículas de Magnetita/uso terapêutico , Masculino , Ratos Wistar , Pele/patologia , Cicatrização
15.
Life Sci ; 258: 118145, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32717270

RESUMO

AIMS: Studies on diabetes mellitus have shown that the phosphoinositide 3-kinase (PI3K)/serine threonine kinase (AKT)/forkhead box protein O1 (FoxO1) signaling pathway can regulate insulin secretion by modulating the expression of pancreatic and duodenal homeobox-1 (PDX-1). Therefore, it was hypothesized that the pathway also played an important role in functional abnormalities of pancreatic islets after severe burns. This study aimed to explore the role and mechanism of the PI3K/AKT/FoxO1/PDX-1 signaling pathway in functional changes of pancreatic islets in rats post severe burns. MAIN METHODS: Rats were grouped, subjected to full thickness burn injuries involving 50% total body surface area (TBSA), and injected intraperitoneally with BPV (HOpic) (0.6 mg/kg) or DMSO (0.55 mg/kg) once a day for three days. Glucose metabolism related indexes were measured by the glucometer, transmission electron microscopy (TEM) and enzyme-linked immunosorbent assay (ELISA). PI3K/AKT/FoxO1/PDX-1 signaling pathway related indexes were detected through immunofluorescence, western blot and RT-qPCR analyses. KEY FINDINGS: Dysglycemia and impaired insulin secretion occurred in rats, the activity of the PI3K/AKT/FoxO1/PDX-1 signaling pathway in the islets fell, and PDX-1 was translocated from the nucleus to the cytoplasm post severe burns. When BPV (HOpic) was used, glucose metabolism and insulin secretion were improved, the activity of the PI3K/AKT/FoxO1/PDX-1 signaling pathway in the islets was up-regulated, and PDX-1 was redistributed from the cytoplasm to the nucleus. SIGNIFICANCE: The activity of the PI3K/AKT/FoxO1/PDX-1 signaling pathway declined following severe burns. When its activity was up-regulated, insulin secretion could be improved, thus ameliorating hyperglycemia.


Assuntos
Queimaduras/patologia , Proteínas de Homeodomínio/metabolismo , Ilhotas Pancreáticas/patologia , Proteínas do Tecido Nervoso/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transativadores/metabolismo , Animais , Queimaduras/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/metabolismo , Masculino , Ratos , Ratos Wistar , Transdução de Sinais
19.
Am J Physiol Cell Physiol ; 319(2): C277-C287, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32432932

RESUMO

Severe burn injury induces a myriad of deleterious effects to skeletal muscle, resulting in impaired function and delayed recovery. Following burn, catabolic signaling and myofiber atrophy are key fiber-intrinsic determinants of weakness; less well understood are alterations in the interstitial environment surrounding myofibers. Muscle quality, specifically alterations in the extracellular matrix (ECM), modulates force transmission and strength. We sought to determine the impact of severe thermal injury on adaptation to the muscle ECM and quantify muscle fibrotic burden. After a 30% total body surface area dorsal burn, spinotrapezius muscle was harvested from mice at 7 (7d, n = 5), 14 (14d, n = 4), and 21 days (21d, n = 4), and a sham control group was also examined (Sham, n = 4). Expression of transforming growth factor-ß (TGFß), myostatin, and downstream effectors and proteases involved in fibrosis and collagen remodeling were measured by immunoblotting, and immunohistochemical and biochemical analyses assessed fibrogenic cell abundance and collagen deposition. Myostatin signaling increased progressively through 21 days postburn alongside fibrogenic/adipogenic progenitor cell expansion, with abundance peaking at 14 days postburn. Postburn, elevated expression of tissue inhibitor of matrix metalloproteinase 1 supported collagen remodeling resulting in a net accumulation of muscle collagen content. Collagen accumulation peaked at 14 days postburn but remained elevated through 21 days postburn, demonstrating minimal resolution of burn-induced fibrosis. These findings highlight a progressive upregulation of fibrogenic processes following burn injury, eliciting a fibrotic muscle phenotype that hinders regenerative capacity and is not resolved with 21 days of recovery.


Assuntos
Queimaduras/genética , Fibrose/genética , Músculo Esquelético/metabolismo , Miostatina/genética , Fator de Crescimento Transformador beta/genética , Animais , Queimaduras/metabolismo , Queimaduras/patologia , Proliferação de Células/genética , Colágeno/genética , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrose/metabolismo , Fibrose/patologia , Regulação da Expressão Gênica/genética , Humanos , Camundongos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/lesões , Músculo Esquelético/patologia , Transdução de Sinais/genética
20.
Ned Tijdschr Geneeskd ; 1642020 05 13.
Artigo em Holandês | MEDLINE | ID: mdl-32406635

RESUMO

This case concerns a girl with geometrically round blisters, mainly on the left arm since 1 month. Histopathologic examination of a skin biopsy showed a necrotic epidermis with subepidermalclefting suggesting thermal damage. Recently, similar thermal burns have been observed more often in adolescents following a so-called 'deo challenge'.


Assuntos
Vesícula/etiologia , Queimaduras/complicações , Queimaduras/diagnóstico , Braço , Biópsia , Vesícula/patologia , Queimaduras/patologia , Criança , Feminino , Humanos , Pele/patologia
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