RESUMEN
This study was designed to investigate the effect of 630 ~ 650-nm red light on treating second-degree burns on lower limbs of glucocorticoid-dependent patients. Sixty-two glucocorticoid-dependent patients with the second-degree burns on lower limbs were divided into the control group (n = 25) and the observation group (n = 37) according to the treatment sequence and the patients' willingness. The patients in both groups were conventionally treated with 1% sulfadiazine silver cream dressing, with the only difference that the observation group received an additional 630-650-nm red light irradiation for 20 min before dressing. Each group was observed for 21 days, and observation ended if the wound healing was terminated. The wound healing rates, wound secretions, marginal response, and pain/itching levels were monitored and assessed. Compared with the control group, the observation group showed higher wound healing rate, fewer wound secretions, and more relief in marginal response. Clinical observation showed that 630-650-nm red light could effectively reduce wound purulent drainage/discharge, relieve the marginal response as well as pain, and promote wound healing.
Asunto(s)
Quemaduras , Terapia por Luz de Baja Intensidad , Humanos , Quemaduras/radioterapia , Glucocorticoides/uso terapéutico , Extremidad Inferior , Dolor/etiología , Dolor/radioterapia , Dolor/tratamiento farmacológico , Sulfadiazina de Plata/uso terapéutico , Cicatrización de HeridasRESUMEN
A key member of the sentrin/small ubiquitin-like modifier (SUMO)-specific protease (SENP) family, SENP2 has been shown to implicate embryonic development, fatty acid metabolism, atherosclerosis, and neurodegenerative diseases. However, other biologic functions of SENP2 and its specific targets are incompletely understood. Here, we uncovered a novel role of SENP2 in negative regulation of keratinocyte migration, a process crucial to wound epithelialization. Defects in this function are often associated with the clinical phenotypes of chronic nonhealing wounds. Mechanistically, SENP2 as a specific de-SUMOylase targets NDR1 (nuclear Dbf2-related 1), also called STK38 (serine-threonine kinase 38), for de-SUMOylation and SUMO conjugation of NDR1 on Lys-465 attenuates its inhibition of p38/ERK1/2 activation by decreasing the association of NDR1 with MEK kinase 1/2. Significantly, low-level laser (LLL) irradiation increases NDR1 SUMOylation and subsequent p38/ERK1/2 activation via down-regulation of SENP2, leading to faster keratinocyte migration. Our findings fill the gaps that linger in the basic mechanisms underlying LLL therapy.-Xiao, N., Li, H., Yu, W., Gu, C., Fang, H., Peng, Y., Mao, H., Fang, Y., Ni, W., Yao, M. SUMO-specific protease 2 (SENP2) suppresses keratinocyte migration by targeting NDR1 for de-SUMOylation.
Asunto(s)
Movimiento Celular , Cisteína Endopeptidasas/metabolismo , Queratinocitos/fisiología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Sumoilación , Ubiquitina/metabolismo , Células Cultivadas , Regulación hacia Abajo , Humanos , Queratinocitos/citología , Proteínas Serina-Treonina Quinasas/metabolismoRESUMEN
BACKGROUND: Acute systemic inflammatory response to severe skin burn injury mediates burn-induced acute lung injury. Ulinastatin is potentially an effective intervention, because it attenuates the systemic inflammatory response induced by endotoxin and improves myocardial function during ischemic shock and reperfusion. METHODS: Rats received full-thickness burn wounds to 30% total body surface area followed by delayed resuscitation. The treatment group received 50,000 U/kg of ulinastatin and the burn group was given vehicle only. A sham group was not burned but otherwise was treated identically. After killing, blood and lung samples were harvested for histology and measurement of inflammatory mediators. RESULTS: Administration of ulinastatin significantly decreased the mRNA and protein levels of tumor necrosis factor-alpha, interleukin-1ß, -6, and -8 both locally and systemically in burn-injured rats. The secretion of neutrophil elastase and myeloperoxidase in the lung and the expression of intercellular adhesion molecule-1 on the surface of lung epithelium were inhibited by ulinastatin. Ulinastatin also reduced the increase in pulmonary microvascular permeability. Consistent with these findings, ulinastatin ameliorated the lung edema and pulmonary oxygenation in burn-injured rats. CONCLUSIONS: These results indicate that the inhibitory effects of ulinastatin on inflammatory mediator production, neutrophil activation, and microvascular permeability are associated with the recovery of pulmonary functions in severe burn-induced acute lung injury and suggest that ulinastatin may serve as a potential therapeutic administration in critical burn care.
Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/etiología , Quemaduras/complicaciones , Glicoproteínas/farmacología , Mediadores de Inflamación/metabolismo , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Inhibidores de Tripsina/farmacología , Lesión Pulmonar Aguda/fisiopatología , Análisis de Varianza , Animales , Quemaduras/fisiopatología , Edema/tratamiento farmacológico , Femenino , Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Elastasa de Leucocito/metabolismo , Pulmón/fisiopatología , Microcirculación/efectos de los fármacos , Peroxidasa/metabolismo , Ratas , Ratas Sprague-Dawley , Pruebas de Función Respiratoria , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Hair follicle stem cells play important roles in maintaining homeostasis and skin tissue self-renewal. Transit-amplifying cells represent the transition of cells from hair follicle stem cells into differentiated epidermal cells. Thus far, the signaling pathway and the molecular biological mechanism that regulate the proliferation and differentiation of hair follicle stem cells remain unclear. In this paper, we studied the relationship between ß-catenin and c-myc during the process of the differentiation of hair follicle stem cells into transit-amplifying cells. Based on our results, the expression of ß-catenin can activate the nuclear gene c-myc and regulate the expression of transit-amplifying cell markers K15, K19, a6-integrin and ß1-integrin, indicating that ß-catenin is involved in the transformation process from hair follicle stem cells to transit-amplifying cells and suggesting that ß-catenin plays an important biological role in the induction of this differentiation process.
Asunto(s)
Diferenciación Celular/genética , Folículo Piloso/citología , Proteínas Proto-Oncogénicas c-myc/biosíntesis , beta Catenina/biosíntesis , Animales , Proliferación Celular/genética , Células Epidérmicas , Epidermis/crecimiento & desarrollo , Regulación del Desarrollo de la Expresión Génica , Folículo Piloso/crecimiento & desarrollo , Humanos , Ratones , Proteínas Proto-Oncogénicas c-myc/genética , Transducción de Señal/genética , Células Madre/citología , Células Madre/metabolismo , beta Catenina/genéticaRESUMEN
A growing number of researches demonstrate that light with a wavelength between 400 and 500nm, namely blue light (BL), has exhibited antibacterial effects on methicillin-resistant Staphylococcus aureus (MRSA) and other microbes. However, there is insufficient evidence to show that BL kills MRSA inside biofilm and the mechanisms underlying the antibacterial effects remain unclear. Here we demonstrate that BL irradiation with 460nm effectively eliminated both planktonic and biofilm MRSA in a dose-dependent manner by utilizing a planktonic MRSA or MRSA biofilm model. Furthermore, using a animal model of skin wound infections with MRSA, we found that 460nm BL showed a therapeutic effect on MRSA infected wounds in mice with significant killing of MRSA, better survival and wound healing. Moreover, RNA sequencing was used to analyze differential gene expressions in MRSA genome after BL irradiation. Our data showed that about one third of up-regulated genes were phage-related. Using phage inhibitor GS-11P, increased prophage activation in MRSA cells induced by BL irradiation was blocked and phage particles were observed. The results indicate that blue visible light irradiation with 460nm is a novel tool for eliminating both planktonic and biofilm MRSA. Prophage activation may be involved in the process. This study may provide a new perspective to understand the antibacterial mechanism by BL.
Asunto(s)
Luz , Staphylococcus aureus Resistente a Meticilina/efectos de la radiación , Profagos/efectos de la radiación , Animales , Biopelículas , Expresión Génica , Ratones , Heridas y Lesiones/fisiopatologíaRESUMEN
Reactive oxygen species (ROS) generated after tissue injury play a crucial role during wound healing through initiating acute inflammation, clarifying infection and dead tissue, and mediating various intracellular signal transduction. Prostaglandin E2 (PGE2) has been identified as one of the major factors responsible for inflammation and tissue repair. In this study, we tested our hypothesis that ROS produced by damaged human keratinocytes induces the synthesis of PGE2. In vitro epithelial wounding model was used to observe the production of ROS and secretion of PGE2 as well as the involved signal pathway. The mechanical injury caused the rapid production of ROS in in vitro cultured keratinocytes, which was significantly blocked by an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase. The increased intracellular ROS caused by mechanical injury stimulates PGE2 production in a time-dependent manner via the activation of cyclooxygenase-2 (COX-2), which was stimulated by phosphorylation of extracellular signal-regulated protein kinase (ERK). These results indicate ROS-induced ERK activation leading to the activation of COX-2 and the synthesis of PGE2 in human keratinocytes responding to mechanical injury in the acute phase.
Asunto(s)
Dinoprostona/metabolismo , Epitelio/patología , Especies Reactivas de Oxígeno/metabolismo , Línea Celular , Ciclooxigenasa 1/metabolismo , Ciclooxigenasa 2/metabolismo , Activación Enzimática , Epitelio/enzimología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , HumanosRESUMEN
In recent years, methicillin-resistant Staphylococcus aureus (MRSA) has become one of the most common multi-drug resistant bacteria in both hospital and community. The aim of this study is to investigate the selective inhibition of MRSA by a modified photosensitizer (LAEtNBS) in vitro and the efficacy of MRSA infection treatment by photodynamic therapy (PDT) with LAEtNBS in vivo. LAEtNBS was synthesized by adding a cationic photosensitizer molecule (EtNBS-COOH) and a quencher molecule to two side chains of cephalosporin, which was then shown to have similar absorption and emission wavelengths with EtNBS-COOH, but suppressed yields of fluorescence quantum and singlet oxygen. The selective inactivation and less phototoxicity of LAEtNBS, compared to that of EtNBS-COOH, were assessed and confirmed by conducting PDT to two Staphylococcus aureus strains and human skin cells at a fluence of 15 J/cm(2) with 640±10 nm LED light. Furthermore, using mouse skin wound model infected with 10(8) CFU of MRSA, we found that both LAEtNBS and EtNBS-COOH were able to treat MRSA infection and enhance wound repair. However, there was no significant difference in the two photosensitizers that might be due to the environment in vivo. Modification of the photosensitizer will be very beneficial for developing new strategies to treat drug resistant bacterial infection with less harm to host tissue.
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Antibacterianos/uso terapéutico , Cefalosporinas/uso terapéutico , Staphylococcus aureus Resistente a Meticilina , Fotoquimioterapia , Fármacos Fotosensibilizantes/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Animales , Antibacterianos/química , Antibacterianos/farmacología , Línea Celular , Células Cultivadas , Cefalosporinas/química , Cefalosporinas/farmacología , Fibroblastos , Humanos , Luz , Masculino , Ratones Endogámicos BALB C , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Piel/lesiones , Cicatrización de Heridas/efectos de los fármacos , beta-LactamasasRESUMEN
This paper reviews the new progress in the research of fractional carbon dioxide laser in treating hypertrophic scar after burn injury, which remains a challenging problem for burn care surgeons. There have been many traditional therapeutic approaches, such as compression remedy, operation, and so on. However, a satisfactory method is lacking to date. In recent years, the newly developed fractional carbon dioxide laser has been employed to treat different kinds of scars, and it has been proved to be effective in terms of an improvement of scar color, texture, and rigidity. It seems to be a promising method for scar treatment in future.
Asunto(s)
Cicatriz/cirugía , Láseres de Gas , Quemaduras/cirugía , Cicatriz Hipertrófica/cirugía , Humanos , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the effectiveness and mechanism of recombinant human granulocyte-macrophage colony-stimulating factor (rhGMCSF) gel on wound debridement and healing of deep II thickness burn. METHODS: Between December 2008 and December 2010, 58 patients with deep II thickness burn, accorded with the inclusive criteria, were collected. There were 36 males and 22 females with an average age of 32.4 years (range, 12-67 years). The causes were hot liquid in 38 cases and fire in 20 cases. The time from injury to treatment was 1-3 days (mean, 2.1 days). In this randomized, double-blind, and self-control study, all patients were randomly divided into 2 groups, wounds were treated with rhGMCSF gel (test group) or gel matrix (control group). There was no significant difference in wound area between 2 groups (P > 0.05). The time of completed removal eschar and the percentage of removal-area of eschar were recorded at 2, 6, 10, 14, and 18 days during healing process. The time of wound healing was also recorded. RESULTS: Compared with control group, the necrotic tissues on the burn wound got soft in test group at 4 days after treatment. At 6 days, they loosened and eventually sloughed off. The wound bed presented in red and white, followed by rapidly growing granulation tissues. Except 18 days after treatment, there were significant differences in the percentage of removal-area of eschar between 2 groups (P < 0.05). The time of completed removal eschar in test group [(7.71 +/- 2.76) days] was significantly shorter than that in control group [(14.71 +/- 3.63) days] (t = 13.726, P = 0.000). The time of wound healing in test group was (18.41 +/- 2.47) days, which was significantly shorter than that in control group [(23.58 +/- 3.35) days] (t = 15.763, P = 0.000). CONCLUSION: Compared with the gel matrix, the rhGMCSF gel may promote wound debridement and healing in deep II thickness burn.
Asunto(s)
Quemaduras/terapia , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Cicatrización de Heridas , Adolescente , Adulto , Anciano , Niño , Desbridamiento , Método Doble Ciego , Femenino , Geles , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos , Adulto JovenRESUMEN
Hydrogen has been reported to selectively quench detrimental reactive oxygen species, particularly hydroxyl radical, and to prevent myocardial or hepatic ischemia/reperfusion injury in multiple models. The aim of this study is to investigate whether hydrogen protects against severe burn-induced acute lung injury in rats. Rats were divided into four groups: sham plus normal saline, burn injury plus normal saline, burn injury plus hydrogen-rich saline, and burn injury plus edaravone. Animals were given full-thickness burn wounds (30% TBSA) using boiling water, except the sham group that was treated with room temperature water. The rats in hydrogen group received 5 ml/kg of hydrogen-rich saline, sham and burn controls obtained the same amount of saline, and the edaravone group was treated with 9 mg/kg of edaravone in saline. Lactated Ringer's solution was given at 6 hours postburn. The lungs were harvested 12 hours postburn for laboratory investigations. Severe burns with delayed resuscitation rapidly caused lung edema and impaired oxygenation in rats. These dysfunctions were ameliorated by administration of hydrogen-rich saline or edaravone. When compared with the burn injury plus normal saline group, hydrogen-rich saline or edaravone group significantly attenuated the pulmonary oxidative products, such as malondialdehyde, carbonyl, and 8-hydroxy-2'-deoxyguanosine. Furthermore, administration of hydrogen-rich saline or edaravone dramatically reduced the pulmonary levels of pulmonary inflammation mediators and myeloperoxidase. Intraperitoneal administration of hydrogen-rich saline improves pulmonary function by reducing oxidative stress and inflammatory response in severe burn-induced acute lung injury.