Exosomes derived from Nr-CWS pretreated MSCs facilitate diabetic wound healing by promoting angiogenesis via the circIARS1/miR-4782-5p/VEGFA axis / 中国天然药物

Mesenchymal stem cell (MSC)-derived exosomes (Exos) were reported to a prospective candidate in accelerating diabetic wound healing due to their pro-angiogenic effect. MSCs pretreated with chemistry or biology factors were reported to advance the biological activities of MSC-derived exosomes. Hence, this study was designed to explore whether exosomes derived from human umbilical cord MSCs (hucMSCs) preconditioned with Nocardia rubra cell wall skeleton (Nr-CWS) exhibited superior proangiogenic effect on diabetic wound repair and its underlying molecular mechanisms. The results showed that Nr-CWS-Exos facilitated the proliferation, migration and tube formation of endothelial cells in vitro. In vivo, Nr-CWS-Exos exerted great effect on advancing wound healing by facilitating the angiogenesis of wound tissues compared with Exos. Furthermore, the expression of circIARS1 increased after HUVECs were treated with Nr-CWS-Exos. CircIARS1 promoted the pro-angiogenic effects of Nr-CWS-Exos on endothelial cellsvia the miR-4782-5p/VEGFA axis. Taken together, those data reveal that exosomes derived from Nr-CWS-pretreated MSCs might serve as an underlying strategy for diabetic wound treatment through advancing the biological function of endothelial cells via the circIARS1/miR-4782-5p/VEGFA axis.

Research advances on the role of nuclear factor-erythroid 2-related factor 2 in wound healing / 中华烧伤杂志

Wound healing is one of the common pathophysiological processes in the body. How to improve the condition of wound healing to promote rapid wound healing has always been a hotspot in research. Oxidative stress is one of the important factors affecting wound healing. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a classic antioxidant stress factor as well as a factor with great potential in facilitating wound healing. The activation of Nrf2 can regulate the downstream antioxidant stress elements and play roles of anti-apoptosis and cell homeostasis maintaining, which improves wound healing environment and promotes wound repair. This paper summarized the common agonists and inhibitors of Nrf2 and reviewed the roles of Nrf2 in promoting skin wound healing including diabetic ulcers, radiation injury, and ischemia-reperfusion injury, etc.

Research advances on the mechanism of extracellular vesicles of adipose-derived mesenchymal stem cells in promoting wound angiogenesis / 中华烧伤杂志

Wound healing involves complex pathophysiological mechanism, among which angiogenesis is considered as one of the key steps in wound healing, and promoting wound angiogenesis can accelerate wound healing. In recent years, mesenchymal stem cell-derived extracellular vesicles have been proven to produce equivalent effects of wound healing promotion comparable to stem cell therapy, with the advantages of low antigenicity and high biocompatibility. The specific mechanism by which extracellular vesicles facilitate wound healing is still not fully understood and is thought to involve all stages of wound healing. This article focuses on the possible mechanism of extracellular vesicles of adipose-derived mesenchymal stem cells in promoting wound angiogenesis, so as to provide ideas for further study on the mechanism of extracellular vesicles to promote wound healing.

Research advances of adipose stem cell matrix gel in promoting wound healing / 中华烧伤杂志

In recent years, with the problem of aging population in China being prominant, the number of patients with chronic wounds such as diabetic foot, pressure ulcer, and vascular ulcer is increasing. Those diseases seriously affect the life quality of patients and increase the economy and care burden of the patients' family, which have been one of the most urgent clinical problems. Many researches have confirmed that adipose stem cells can effectively promote wound healing, while exogenous protease is needed, and there are ethical and many other problems, which limit the clinical application of adipose stem cells. Adipose stem cell matrix gel is a gel-like mixture of biologically active extracellular matrix and stromal vascular fragment obtained from adipose tissue by the principle of fluid whirlpool and flocculation precipitation. It contains rich adipose stem cells, hematopoietic stem cells, endothelial progenitor cells, and macrophages, etc. The preparation method of adipose stem cell matrix gel is simple and the preparation time is short, which is convenient for clinical application. Many studies at home and abroad showed that adipose stem cell matrix gel can effectively promote wound healing by regulating inflammatory reaction, promoting microvascular reconstruction and collagen synthesis. Therefore, this paper summarized the preparation of adipose stem cell matrix gel, the mechanism and problems of the matrix gel in promoting wound repair, in order to provide new methods and ideas for the treatment of chronic refractory wounds in clinic.

Research advances in role of angiogenesis in diabetic ulcer and traditional Chinese medicine intervention / 中国中药杂志

Diabetic ulcer(DU) is one of the common complications of diabetes often occurring in the peripheral blood vessels of lower limbs or feet with a certain degree of damage. It has high morbidity and mortality, a long treatment cycle, and high cost. DU is often clinically manifested as skin ulcers or infections in the lower limbs or feet. In severe cases, it can ulcerate to the surface of tendons, bones or joint capsules, and even bone marrow. Without timely and correct treatment, most of the patients will have ulceration and blackening of the extremities. These patients will not be able to preserve the affected limbs through conservative treatment, and amputation must be performed. The etiology and pathogenesis of DU patients with the above condition are complex, which involves blood circulation interruption of DU wound, poor nutrition supply, and failure in discharge of metabolic waste. Relevant studies have also confirmed that promoting DU wound angiogenesis and restoring blood supply can effectively delay the occurrence and development of wound ulcers and provide nutritional support for wound healing, which is of great significance in the treatment of DU. There are many factors related to angiogenesis, including pro-angiogenic factors and anti-angiogenic factors. The dynamic balance between them plays a key role in angiogenesis. Meanwhile, previous studies have also confirmed that traditional Chinese medicine can enhance pro-angiogenic factors and down-regulate anti-angiogenic factors to promote angiogenesis. In addition, many experts and scholars have proposed that traditional Chinese medicine regulation of DU wound angiogenesis in the treatment of DU has broad prospects. Therefore, by consulting a large number of studies available, this paper expounded on the role of angiogenesis in DU wound and summarized the research advance in traditional Chinese medicine intervention in promoting the expression of angiogenic factors [vascular endothelial growth factor(VEGF), fibroblast growth factor(FGF), and angiopoietin(Ang)] which played a major role in promoting wound angiogenesis in the treatment of DU to provide ideas for further research and new methods for clinical treatment of DU.

Retratamiento y reparación de una perforación radicular. Informe clínico, radiográfico e histológico / Retreatment and healing of a case of root perforation. Clinical, radiographic and histological report

Objetivo: Describir los aspectos clínicos, radiográfi- cos e histológicos del retratamiento realizado en un segundo molar superior en el que se había producido previamente una perforación radicular durante el tratamiento original. Caso clínico: Un paciente masculino de 50 años con- currió a la consulta para realizar un retratamiento endodóntico en un segundo molar superior derecho. El examen radiográfi- co reveló la presencia de un tratamiento incompleto, un área radiolúcida periapical y una perforación radicular producida por un poste roscado insertado fuera del espacio del conducto mesio vestibular. Una vez retirado el poste, se selló la perfo- ración con Biodentine y se realizó el retratamiento. Luego de dos años, el paciente regresó a la consulta con dolor a la mas- ticación, localizado en el área correspondiente al segundo mo- lar superior derecho previamente tratado. Durante el examen clínico y radiográfico se detectó la presencia de una fractura vertical en la raíz palatina. A causa del severo compromiso radicular el molar fue extraído y derivado para su análisis his- tológico. El informe del laboratorio reveló que la perforación había sido reparada por medio de la aposición de un nuevo tejido calcificado y que el remanente periodontal adherido a la raíz se encontraba dentro de los límites normales. El presente caso clínico resalta la importancia que tiene el conocimiento cabal de la anatomía del sistema de conductos radiculares con el objeto de evitar errores de procedimiento que puedan influir negativamente en el pronóstico del tratamiento (AU)

Aim: To describe the clinical, radiographic and histo- logical aspects of the retreatment of a second upper molar in which root perforation had occurred during the original treatment. Clinical case: A 50-year old male was referred for endo- dontic retreatment of the right second maxillary molar. Radi- ographic examination revealed the presence of an incomplete root canal treatment, a radiolucent periapical area and a root perforation produced by a threaded post placed outside of the mesiobuccal root canal. After post removal, the root perfo- ration was sealed with Biodentine and the root canals were retreated. Two years later, the patient returned to the office com- plaining of severe pain during mastication, in the area of the previously retreated right second maxillary molar. Clinical and radiographic examination revealed the presence of a ver- tical fracture on the palatal root. Since this kind of root dam- age non-restorable, the tooth was extracted and submitted to histologic analysis. The laboratory report revealed that the perforation site had healed by the apposition of new calci- fied tissue, and that the remnants of periodontal tissue which persisted attached to the root were within normal limits. This clinical case highlights the importance of thorough knowl- edge of the anatomy of the root canal system in order to avoid procedural errors which may compromise the prognosis of the treatment (AU)

Research advances on mesenchymal stem cell-derived extracellular vesicles in promoting angiogenesis of diabetic ulcers / 中华烧伤杂志

Extracellular vesicles are nanoparticles secreted by most eukaryotic cells and play important roles in material transport and information transmission between cells, involved in inflammation, angiogenesis, antigen presentation, cell apoptosis, cell differentiation, and other biological processes. The culture supernatant of mesenchymal stem cells is rich in extracellular vesicles, and the extracellular vesicles can regulate the formation of new blood vessels, a key step in wound healing and tissue repair. The persistence of diabetic ulcers is closely related to the blocked formation of wound vascular network. This article reviews the role of extracellular vesicles derived from mesenchymal stem cells in promoting angiogenesis of diabetic ulcers, in order to provide a new idea for the treatment of diabetic ulcers.

Research advances on thymosin β4 in promoting wound healing / 中华烧伤杂志

With the aging of population and the development of social economy, the incidence of chronic wounds is increasing day by day, while the incidence of burns and trauma remains at a high level, making wound repair an increasingly concerned area in clinical practice. Thymosin β4 is a naturally occurring small molecule protein in vivo, which is widely distributed in a variety of body fluids and cells, especially in platelets. Thymosin β4 has biological activities of promoting angiogenesis, anti-inflammation, anti-apoptosis, and anti-fibrosis, and has many important functions in wound repair. Thymosin β4 has been observed to promote the healing of various wounds, such as burns, diabetic ulcers, pressure ulcers. This paper will review the molecular structure, mechanism of wound healing promotion, pharmacokinetics, and clinical application of thymosin β4, aiming to introduce its potential in wound treatment and the shortcomings of current researches.

Research advances on stem cell therapy for diabetic foot wounds / 中华烧伤杂志

Diabetic foot wound repair is a challenging issue in clinical practice. Due to the influence of multiple factors including the damage and regeneration failure of local tissue, the impaired pathways of wound repairing through blood vessels and nerve nutrition, and disorders of a variety of cellular factors, traditional treatment methods are often difficult to achieve good therapeutic effects. Stem cells are a type of cells with potentials of multidirectional differentiation, which also possess functions such as regulating immunity and paracrine to facilitate the comprehensive wound repair, so they have promising application prospect at present for the treatment of diabetic foot wounds. Because the relevant parameters of stem cell treatment are in the exploratory phase, there were no standardized data. This paper reviews the application of stem cells in the research of diabetic foot wound treatment over the past 6 years, analyzing and summarizing the contents in focused aspects including the types and sources of stem cells, effects of donor age and gender on stem cells, mode of administration, transplantation survival rate and safety, which may provide a reference for further application of stem cells in the clinical treatment of diabetic foot wound.

Ulmoplus® increases FGF-2 expression and promote burn wound healing / Ulmoplus® incrementa la expresión de FGF-2 y promueve la cicatrización de heridas por quemadura

SUMMARY: The role of fibroblast growth factor (FGF) in the wound repair process has been described, particularly during the stimulation of angiogenesis in the proliferative phase. Ulmo honey (Eucryphia cordifolia) has demonstrated important bactericidal, fungicidal, antioxidant and healing properties. Ulmoplus®, a honey-based medicinal product, accelerates healing time and promotes fibroblast activation and collagen fiber production. The aim of this study was to evaluate the immunohistochemical expression of endogenous FGF-2 in burns treated with Ulmoplus® vs. the gold standard (hydrogel-tull), and Ulmo honey as the first step to clarifying the regulatory mechanism of this therapeutic option. 15 adult guinea pigs (Cavia porcellus) were used, divided into three groups: C+: positive control treated with hydrogel-tull (gold standard); E1: experimental group treated with Ulmo; and E2: experimental group treated with Ulmoplus®. A deep uniform burn was made under anesthetic that covered 1 cm2 of the skin on the back of each animal. The daily treatments were administered with hydrogel-tull, Ulmo honey or Ulmoplus®, where appropriate. On treatment day 10 the biopsies were taken and processed for histological and immunohistochemical analysis. The immunolabeling was quantified through an integrated optical density (IOD) analysis, expressed as lum/ µm2 using the Image- ProPremier 9.1 software. The endogenous expression of FGF-2 was consistent with the stage of healing presented by the study groups, varying in its localization and IOD intensity. The E2 group presented a significantly higher IOD (60053.55 ± 59877.84 lum/µm2) than the C+ (p = 0.001) and E1 (p = 0.001) groups. Our findings indicated that the medicinal Ulmoplus® honey is effective at facilitating wound closing, and the promoter effect of FGF-2 expression accelerated the healing process compared to the treatments with hydrogel-tull (gold standard) and Ulmo honey.

RESUMEN: Se ha descrito el papel del factor de crecimiento fibroblaástico (FGF) en el proceso de reparación de heridas, particularmente durante la estimulación de la angiogénesis en la fase proliferativa. La miel de Ulmo (Eucryphia cordifolia) ha demostrado importantes propiedades bactericidas, fungicidas, antioxidantes y cicatrizantes. Ulmoplus®, un medicamento a base de miel, acelera el tiempo de cicatrización y promueve la activación de fibroblastos y la producción de fibras colágenas. El objetivo de este estudio fue evaluar la expresión inmunohistoquímica del FGF-2 endógeno en quemaduras tratadas con Ulmoplus® frente al gold standard (hidrogel-tull) y miel de Ulmo como primer paso para esclarecer el mecanismo regulador de esta opción terapéutica. Se utilizaron 15 cobayas adultos (Cavia porcellus), divididos en tres grupos: C +: control positivo tratado con hidrogel-tull (gold standard); E1: grupo experimental tratado con Ulmo; y E2: grupo experimental tratado con Ulmoplus®. Se realizó una quemadura profunda uniforme bajo anestesia que cubrió 1 cm2 de la piel del lomo de cada animal. Los tratamientos diarios se administraron con hidrogel-tull, miel de Ulmo o Ulmoplus®, en cada caso. El día 10 de tratamiento se tomaron biopsias y se procesaron para análisis histológico e inmunohistoquímico. El inmunomarcaje se cuantificó mediante análisis de densidad óptica integrado (DOI), expresado como lum/µm2 utilizando el software Image-ProPremier 9.1. La expresión endógena de FGF-2 fue consistente con la etapa de cicatrización presentada por los grupos de estudio, variando en su localización e intensidad de DOI. El grupo E2 presentó una DOI significativamente mayor (60053,55 ± 59877,84 lum/µm2) que los grupos C + (p = 0,001) y E1 (p = 0,001). Nuestros hallazgos indicaron que la miel de uso médico Ulmoplus® es eficaz para facilitar el cierre de heridas, y el efecto promotor de la expresión de FGF-2 aceleró el proceso de curación en comparación con los tratamientos con hidrogel-tull (gold standard) y miel de Ulmo.

Endodoncia y ortodoncia. Parte 2: casos clínicos / Endodontics and orthodontics. Part 2: clinical cases

Objetivo: Describir el tratamiento endodóncico de cuatro casos clínicos de reabsorción radicular desarrollada durante o tras un tratamiento ortodóncico. Casos clínicos: Después de la preparación y la desinfección de los conductos radiculares, estos fueron obturados por un tiempo prudencial con una medicación intraconducto de hidróxido de calcio, que luego fue reemplazada por MTA. Luego de un período de entre uno y cuatro años, según el caso, los tratamientos fueron evaluados clínica y radiográficamente. Los dientes que debieron ser extraídos fueron analizados histológicamente. Según la evolución clínica y radiográfica de los casos presentados, el uso inicial de hidróxido de calcio y su posterior reemplazo por MTA parecería ser un protocolo adecuado para completar el proceso de reparación de los tejidos apicales y perirradiculares en casos de reabsorciones radiculares provocadas por fuerzas ortodóncicas excesivas. Las enfermedades sistémicas deben ser tenidas en cuenta para la elección de la terapéutica (AU)

Aim: To describe the endodontic treatment of four clinical cases of permanent teeth suffering root resorption during or after orthodontic treatment. Clinical cases: Four clinical cases of permanent teeth with root resorption were endodontically treated. After the root canals were prepared and disinfected, they were medicated with calcium hydroxide. After an appropriate observation period, the canals were finally filled with MTA. The treatment outcomes were clinically and radiographically assessed at an interval between one to four years according to the clinical case. The histological findings of teeth that required extraction was also described. Our clinical and radiographic observations suggest that a temporary filling with calcium hydroxide and further obturation with MTA can provide a favorable intracanal environment for apical and periradicular tissue reparation. The clinician needs a full medical history to be aware of the systemic diseases in patients with root resorption that will be of importance for the proper selection of treatment (AU)

Scar-free wound healing following full-thickness cutaneous wounding in the tail and body of Scincella tsinlingensis / Cicatrización de heridas sin cicatrices luego de heridas cutáneas de espesor total en la cola y el cuerpo de Scincella tsinlingensis

SUMMARY: The cutaneous wounds of trunk and tail healing scar-free or with scar were different in lizard species. Full- thickness cutaneous injuries of tail and body of Scincella tsinlingensis were examined by histomorphological and immunohistochemistrical methods. The results showed that all injuries healed without scarring. The process of the wound healing of S. tsinlingensis involved hemostasis, re-epithelialization, proliferation and remodelling, which also could be further subdivided into six stages. Stage I, 0-2 day post wound (dpw), the blood oozed gradually, no obvious wound contraction, minimal blood loss. Stage II, 2-10 dpw, the wound bed covered by the fibrin clot of blood, tissue fluid and tissue debris. Stage III, 7d-15 dpw, the wrinkled wound epitheliums was gradually stratified, and its surface was keratinized and exfoliated. Stage IV, 10-28 dpw, pigment cells were distributed at the boundary between epidermis and dermis, with few blood vessels and no granulation tissue formation. Stage V, 20-70 dpw, opaque scales covered the wound epithelium with randomly scattered melanophores in the base of the epidermis. Stage VI, 45-135 dpw, the epidermis and dermis restored to the thickness of the original skin. Regenerated scales were similar to scales of the uninjured dermis. The positive immunostaining of matrix metalloproteinases-9, cytokeratin 6, alpha smooth muscle actin, caspase 3 and transforming growth factor-β3 showed the specificity of healing period and different stages, which participated in skin wounds healing of S. tsinlingensis.

RESUMEN: En las diferentes especies de lagartos las heridas cutáneas del tronco y la cola sin cicatrices, o con algún tipo de cicatriz son diversas. En este estudio se examinaron las heridas cutáneas de espesor total de la cola y el cuerpo de Scincella tsinlingensis mediante métodos histomorfológicos e inmunohistoquímicos. Los resultados indicaron que todas las lesiones sanaron sin cicatrices visibles. El proceso de cicatrización de heridas de S. tsinlingensis implicó hemostasia, reepitelización, proliferación y remodelación, que también podrían subdividirse en seis etapas. Etapa I, 0-2 días después de la herida (dph), la sangre filtraba gradualmente, sin contracción evidente de la herida, con pérdida mínima de sangre. Etapa II, 2-10 dph, el lecho de la herida estaba cubierto por el coágulo de sangre, líquido tisular y restos tisulares de fibrina. Etapa III, 7-15 dph, los epitelios de la herida se estratificaron gradualmente y su superficie se queratiniza y exfolia. Etapa IV, 10-28 dph, las células pigmentarias se distribuyeron en el límite entre la epidermis y la dermis, con pocos vasos sanguíneos y sin formación de tejido de granulación. Etapa V, 20-70 dph, escamas opacas cubrieron el epitelio de la herida con melanóforos dispersos al azar en la base de la epidermis. Etapa VI, 45-135 dph, la epidermis y la dermis restauradas al grosor de la piel original. Las escamas regeneradas eran similares a las escamas de la dermis sin herida. La inmunotinción positiva de metaloproteinasas- 9 de matriz, citoqueratina 6, actina de músculo liso alfa, caspasa 3 y factor de crecimiento transformante-β3 mostró la especificidad del período de curación y las diferentes etapas, que participaron en la curación de heridas cutáneas de S. tsinlingensis.

Uso da túnica vaginal canina conservada em glicerina a 98% como curativo biológico no tratamento de feridas cutâneas produzidas em ratos Wistar / Use of canine vaginal tunic preserved in 98% glycerin as biological curative in the treatment of skin produced in wound Wistar rats

Na procura por material alternativo no tratamento de feridas cutâneas, buscou-se com este estudo avaliar o comportamento da túnica vaginal canina conservada em glicerina a 98% como curativo biológico no tratamento de feridas cutâneas provocadas experimentalmente em ratos. Foram utilizados 16 ratos Wistar, nos quais foram induzidas experimentalmente duas lesões cutâneas na região dorsal, sendo uma cranial e a outra caudal. Uma ferida serviu de controle, a qual não recebeu tratamento, a outra recebeu a túnica vaginal recobrindo toda extensão da lesão. A seleção de qual das feridas, cranial ou caudal, iria receber a membrana foi feita de forma aleatória. Os animais foram distribuídos em quatro grupos de igual número para análises clínicas, macroscópicas e histológicas decorridos três, sete, 14 e 21 dias de pós-operatório. Na avaliação clínica e macroscópica pode-se observar que o processo de reparação teve evolução semelhante tanto no grupo controle quanto no grupo membrana. Na análise histopatológica foi constatada grande quantidade de infiltrado inflamatório nos períodos iniciais, no entanto, decorridos 21 dias, a epiderme já se encontrava reparada, e em todos os momentos foi observada maior presença de tecido conjuntivo no grupo membrana, sugerindo maior precocidade na cicatrização. Deste modo, concluiu-se que a túnica vaginal canina pode ser utilizada como nova alternativa no tratamento de feridas cutâneas.

In the search for alternative material in the treatment of cutaneous wounds, this study aimed to evaluate the behavior of canine vaginal tunic conserved in glycerin 98% as a biological dressing in the treatment of cutaneous wounds provoked experimentally in rats. Sixteen animals were used in which two cutaneous lesions were caused in the dorsal region, one cranial and the other caudal. One wound served as a control which did not receive treatment, the other received the vaginal tunic covering all extension of the lesion. The selection of which of the wounds, cranial or caudal, would receive the membrane was made at random. The animals were divided into four groups of equal numbers for clinical, macroscopic, and histological analyzes after three, seven, 14 and 21 postoperative days. In the clinical and macroscopic evaluation, it can be observed that the healing process had similar evolution in both the control group and the membrane group. In the histopathological analysis, a large amount of inflammatory infiltrate was observed in the initial periods; however, after 21 days the epidermis was already healed, and at all times a greater presence of connective tissue was observed in the membrane group, suggesting a greater precocity in healing. Thus, it was concluded that the canine vaginal tunic can be used as a new alternative in the treatment of cutaneous wounds.

Tratamiento regenerativo de lesión interproximal consecuente a fractura del tercio medio en diente permanente joven / Regenerative treatment of interproximal lesion following middle third fracture in a young permanent tooth

Se presenta un caso clínico de fractura radicular del tercio medio, de pieza 2.1 con desplazamiento de los cabos de fractura. Es tratado con un novedoso procedimiento terapéutico, mediante la utilización de un biomaterial de tercera generación osteoconductor, osteogénico y osteoinductor. Se obtiene la reparación del tejido conectivo interproximal y la formación de tejido calcificado (AU)

We present a clinical case of root fracture of the middle third, piece 2.1 with displacement of the fracture ends. It is treated with a novel therapeutic procedure, using a thirdgeneration osteoconductive, osteogenic and osteoinductive biomaterial. Interproximal connective tissue repair and calcified tissue formation are obtained (AU)

Molecular mechanisms in the process of re-epithelization in wound healing and the action of honey in keratinocytes / Mecanismos moleculares en el proceso de re-epitelización en cicatrización de heridas y la acción de la miel en queratinocitos

SUMMARY: The treatment of chronic wounds has become a public health issue in recent years mainly due to comorbidities associated with an older population and bacterial resistance. Honey has emerged as an alternative treatment for chronic wounds but lack of knowledge of its mechanism of actionin the treated tissue and low quality of evidence in clinical triads has distanced the medical community from honey as a possible treatment. One of the main processes that is altered in chronic wounds is re-epithelialization mediated by keratinocytes, where proliferation and migration processes are altered. Markers of proliferation, migration and activation of keratinocytes, such as adhesion molecules, growth factors, membrane receptors, signal translating proteins, transcription factors, microRNAs, among others are deregulated in this process. In general, honeys from different floral origins have a positive effect on markers of proliferation and migration in keratinocytes. In conclusion there are still few studies that focus on the molecular action of honey in keratinocytes and fail to report details on the honey used not allowing to achieve the same results.

RESUMEN: El tratamiento de heridas crónicas (HC) se ha vuelto un tema de salud pública en los últimos años, principalmente debido a comorbilidades asociadas a una población de mayor edad y a la resistencia bacteriana. La miel ha surgido como un tratamiento alternativo para HC pero la falta de conocimiento de su mecanismo de acción en el tejido tratado y de la baja calidad de la evidencia en triadas clínicas, ha distanciado a la comunidad médica de la miel como posible tratamiento. Uno de los principales procesos que se ve alterado en las HC es la re-epitelización mediada por queratinocitos, donde se ven alterados los procesos de proliferación y migración. Marcadores de proliferación, migración y activación de queratinocitos, como moléculas de adhesión, factores de crecimiento, receptores de membrana, proteínas traductores de señales, factores de transcripción, microARNs, entre otras, se ven desreguladas en éste proceso. De manera general las mieles de diferentes orígenes florales tienen un efecto positivo en marcadores de proliferación y migración en queratinocitos. En conclusión aún existen pocos estudios que se enfoquen en la acción molecular de la miel en queratinocitos y los pocos que existen fallan en la entrega de información en relación a la miel utilizada que pueda hacer reproducibles los resultados.

Granuloma periférico de células gigantes asociado a un implante: informe de un caso clínico con seguimiento a 5 años / Implant-associated peripheral giant cell granuloma: a case report with 5-year follow-up

Objetivo: Presentar la respuesta clínica a largo plazo del tratamiento de un granuloma periférico de células gigantes en un implante oseointegrado en el maxilar inferior. Caso clínico: Un paciente de 60 años, de sexo masculino, sin antecedentes sistémicos, concurrió por una lesión con márgenes definidos, de color rojizo morado y consistencia blanda sobre los tejidos blandos en la cara vestibular de un implante colocado en zona de 46. Se realizó la escisión quirúrgica de la lesión, se procesó el tejido extirpado y se envió al laboratorio. El estudio anatomopatológico confirmó el diagnóstico de granuloma periférico de células gigantes. La lesión recidivó dos veces. En la tercera extirpación se realizó la implantoplastía de la superficie del implante. La cicatrización no presentó inconvenientes. Hasta el último control, a los 5 años, no volvió a haber recidiva. Conclusión: En este caso clínico, se logró mantener la salud periimplantaria durante 5 años luego de la eliminación de un granuloma periférico de células gigantes. No obstante, este tuvo que ser removido en tres oportunidades debido a la alta recidiva (AU)

Aim: To evaluate the long-term clinical response to the treatment of a peripheral giant cell granuloma in an osseointegrated implant in the lower jaw. Clinical case: A 60-year-old male patient, with no systemic medical problems, presented a soft tissue lesion located at the buccal aspect of an implant placed in the 46 area. The lesion had defined reddish-purple margins and soft consistency. Surgical excision of the lesion was performed, processed and sent to the laboratory. The histopathology confirmed the diagnosis of peripheral giant cell granuloma. The lesion recurred twice. During the third surgical removal an mplantoplasty of the implant surface was performed. The healing was uneventful and there was no recurrence until the last control at 5 years. Conclusion: In this clinical case, perimplantar gingival health was maintained for 5 years after the surgical removal of a giant cell peripheral granuloma. However, it had to be removed three times, demonstrating a high recurrence (AU)

Análise ultraestrutural do colágeno de feridas cutâneas de coelhos tratadas com plasma rico em plaquetas de equino / Ultrastructural analysis of the collagen of rabbit skin wounds treated with platelet-rich equine plasma

O colágeno é sintetizado e segregado no espaço extracelular e organizados em fibrilas estriadas de acordo com o tipo de tecido. Utilizaram-se 24 coelhos brancos da raça Nova Zelândia, com idade de 12 meses e com 3,0kg de peso corporal, para avaliar a porcentagem de colágeno das feridas cutâneas tratadas com plasma rico em plaquetas de equino e pomada contendo gentamicina, sulfanilamida, sulfadiazina, ureia e vitamina A. Os animais foram separados em quatro grupos de igual número e submetidos à remoção de pele na região das linhas médias dorsal torácica (feridas tratadas) e lombar (feridas controle). As feridas torácicas foram tratadas com plasma rico em plaqueta de equino e pomada contendo gentamicina, sulfanilamida, sulfadiazina, ureia e vitamina A, e as do grupo controle somente com a pomada. Dos animais do grupo I, foi coletado tecido cutâneo, para a avaliação histológica e a ultraestrutural, com três dias de pós-operatório; dos animais do grupo II, com sete dias; do grupo III, com 14 dias; e do grupo IV, com 21 dias. Decorrido o período de avaliação de cada grupo, foi coletado fragmento de pele para avaliação da porcentagem de colágeno, bem como do diâmetro e da densidade da fibrila de colágeno por microscopia eletrônica de transmissão. O tratamento com PRP de equino associado à aplicação tópica da pomada mostrou-se eficaz na maturação das fibrilas colágenas e na antecipação do processo cicatricial.(AU)

Collagen is synthesized and secreted into the extracellular space and organized into striated fibrils according to the tissue type. This study evaluated the concentration of collagen in rabbit skin wounds treated with equine platelet-rich plasma (PRP) and ointment containing gentamicin, sulfanilamide, sulfadiazine, urea, and vitamin A. Twenty-four New Zealand white rabbits aged 2 to 12 months and weighing 3.0kg were included. The animals were allocated equally into four groups and the skin was removed from the thoracic dorsal midline (treated wound) and lumbar (control wound) regions. The thoracic wounds were treated with equine PRP and ointment containing gentamicin, sulfanilamide, sulfadiazine, urea, and vitamin A, and the control group was treated with the ointment alone. For histological and ultrastructural assessment, cutaneous tissue was collected on postoperative days 3 (group I), 7 (group II), 14 (group III), and 21 (group IV). After the evaluation period, in each group, a skin fragment was collected for analysis of the collagen concentration, as well as the collagen fibril diameter and density by transmission electron microscopy. The results indicated that treatment with equine PRP combined with topical application of the ointment was effective in facilitating the maturation of collagen fibrils and the wound healing process.(AU)

Células-tronco mesenquimais de origem adiposa na fase de proliferação do processo de cicatrização de queimaduras frias / Adipose-derived stem cells in the proliferation phase of the healing process in cold burns

A criocirurgia tem sido utilizada no tratamento de diferentes enfermidades de sistemas e órgãos. Contudo, são relatados efeitos adversos, como cicatrização lenta, cicatrizes extensas, disfunção estética e funcional. As lesões que ocorrem naturalmente pela exposição ao frio extremo, comumente, resultam em gangrena. O presente trabalho teve como objetivo avaliar a influência das células-tronco mesenquimais de origem adiposa (ADSCs) na fase de proliferação da cicatrização de feridas cutâneas. Por meio da aplicação do nitrogênio líquido pela técnica do spray aberto, realizou-se a indução de uma ferida, de aproximadamente 15mm de diâmetro, na região dorsal de cada rato. A ferida recebeu o tratamento de acordo com o grupo ao qual pertencia: 1) aplicação das ADSCs no 15º dia (grupo tratado); 2) aplicação da solução cloreto de sódio 0,9% no 15º dia (grupo sham); 3) nenhuma intervenção até o momento da eutanásia (grupo controle). O grupo tratado com as ADSCs apresentou as maiores taxas de contração média das feridas e obteve diferença estatisticamente significativa em relação ao grupo sham quanto à neovascularização. A terapia com as ADSCs proporcionou uma relevante evolução clínica das feridas, podendo ser constatada ao final do período de avaliação por cicatrizes mais estreitas e compridas.(AU)

Cryosurgery has been used to treat different diseases of systems and organs, although adverse effects have been reported such as delayed wound healing, large scars, esthetical deformation and functional impairment. Injuries caused naturally by the exposure to extreme cold weather conditions mostly result in gangrene. This study aims to evaluate the influence of adipose-derived stem cells (ADSCs) in the proliferation phase on cutaneous wound healing. Through the application of liquid nitrogen by the spraying technique, a 15 millimeter diameter lesion was produced in the dorsal region of each rat. The wound received treatment according to the group it belonged: 1) ADSCs application on the 15th day (treated group); 2) application of 0.9% sodium chloride solution on the 15th day (sham group); 3) no intervention until euthanasia (control group). The group treated with ADSCs showed the highest wound average contraction rate; this group got a significant statistical difference in relation to the sham group when it refers to neovascularization. The ADSCs therapy provides an important clinical evolution of wounds. This was verified at the end of the evaluation period through narrower and longer scars.(AU)

Terapia regenerativa en un incisivo central superior permanente inmaduro: caso clínico / Regenerative therapy in an immature permanent upper central incisor: a clinical case

Objetivo: Presentar la terapia regenerativa como una al- ternativa para la resolución de un caso de traumatismo denta- rio en un diente permanente incompletamente desarrollado. Caso clínico: Se realizó el tratamiento de un incisivo central superior con mortificación pulpar y periodontitis api- cal aguda subsecuente a trauma dental en un paciente de 8 años de edad. Se aplicó el protocolo de regeneración pulpar recomendado por la Asociación Americana de Endodoncia. Se estimuló la formación de un coágulo en el interior del con- ducto a partir de los tejidos periapicales, previa desinfección con la pasta triple antibiótica, y finalmente se colocó mineral trióxido agregado coronal a este. Se obtuvo así una matriz es- teril que permitió el crecimiento de nuevo tejido y se realiza- ron controles periódicos durante 4 años. Se constató silencio clínico. Radiográficamente, se observó la formación de tejido sobre las paredes del conducto y el cierre apical. Conclusión: La terapia regenerativa como alternativa de tratamiento, en este caso, permitió la disminución de la luz del conducto por el depósito de tejidos calcificados y el cierre del foramen apical, mejorando el pronóstico de la pieza dentaria (AU)

Aim: To present pulp regeneration therapy as an alter- native to resolve dental trauma in immature permanent teeth. Clinical case: We report a clinical case of an immature central superior incisor with pulp mortification and acute api- cal periodontitis subsequent to dental trauma, in an 8 year old patient. The pulp Regeneration protocol recommended by the American Endodontics Association was applied. We stimulated a clot formation inside the duct from periapical tissues and after disinfection with a mixture of three antibi- otics mineral trioxide aggregated was finally place coronal to the clot. Thus a sterile matrix was obtained that allowed new tissue's growth. Periodic check-up visits were carried out over a 4 years period. Clinical silence was observed. Tissue formation on duct walls and apical closure were radiograph- ically detected (AU) Conclusion: Regenerative therapy is an alternative for the treatment of immature permanent teeth, in ths clinical case it allowed the reduction of the width of the duct by the opposition of hard tissues and the closure of the apical fora- men improving the forecast of these teeth.

Effect of supplementation with probiotics on colonic anastomoses in rats: morphological and tensiometric study / Efeito da suplementação com probióticos em anastomoses colônicas de ratos: estudo morfológico e tensiométrico

ABSTRACT Background: The use of probiotics positively modifies the composition and function of intestinal flora, improving the quality of intestinal anastomosis. Aim: To evaluate the impact of probiotic use on intestinal anastomosis of rats. Method: Thirty-six adult male Wistar rats (Rattus norvegicus albinus, Rodentia Mammalia) were used, with body weight ranging from 220-320 g. The animals were housed and acclimated individually in boxes receiving water and ration ad libitum. After initial acclimatization, the control group received perioperative ration ad libitum for 12 days (seven preoperatively and five postoperatively) associated with the maltodextrin formula at a dose of 250 mg/day in isocaloric and isovolumetric form. Likewise, the probiotic group received oral supplementation of probiotics dose of 250 mg/day, associated with isocaloric and isovolumetric diet. The probiotic chosen for this study was composed of strains (doses 1x109 CFU/g)12 Lactobacillus paracasei LPC-37, Bifidobacterium lactis HN0019, Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus NCFM. Probiotics or placebo were administered orally with the aid of a dosimeter spatula. Both groups underwent two colostomies, one in the right colon and the second in rectosigmoid, followed by reanastomosis with eight separate 6-0 mononylon stitches. The sacrifice took place on the fifth day. The parameters evaluated included tensile strength, histology and collagen densitometry. Results: The rate of intestinal fistula for the control and probiotic groups were, respectively, 22.22% and 11.11% (p=0.6581).Perioperative supplementation with probiotics increased collagen deposition of types I and III (p<0.0001), improved maximum traction force and maximum rupture force, p=0.0250 and p=0.0116 respectively, fibrosis area (p<0.0001), and area of the inflammatory infiltrate (p=0.0115). Conclusions: The use of probiotics had a positive impact on the quality of intestinal anastomosis.

RESUMO Racional: A utilização de probióticos modifica positivamente a composição e função da flora intestinal melhorando a qualidade da anastomose intestinal. Objetivo: Avaliar o impacto da utilização de probióticos na anastomose intestinal de ratos. Método: Foram utilizados 36 ratos Wistar (Rattus norvegicus albinus, Rodentia Mammalia), machos adultos, com peso corporal variando entre 220 e 320 g. Os animais foram alojados e aclimatados individualmente em caixas recebendo água e ração ad libitum. Após aclimatação inicial, o grupo controle recebeu perioperatoriamente ração ad libitum por 12 dias (sete no pré-operatório e cinco no pós-operatório) associado à fórmula de maltodextrina na dose de 250 mg/dia de forma isocalórica e isovolumétrica. Na semana que precedeu o procedimento cirúrgico (período de sete dias) e no pós-operatório (por cinco dias), os ratos do grupo estudo receberam suplementação via oral de probióticos dose de 250 mg/dia, associado à dieta isocalórica e isovolumétrica. O probiótico utilizado era composto pelas cepas (doses 1x109 UFC/g)12 Lactobacillus paracasei LPC-37, Bifidobacterium lactis HN0019, Lactobacillus rhamnosus HN001 e Lactobacillus acidophilus NCFM. A administração de probiótico ou placebo foi realizada via oral, com auxílio de espátula com dosímetro. Os dois grupos foram submetidos à duas colostomias, uma em cólon direito e outra em retossigmóide, seguido de reanastomose com oito pontos separados de mononylon 6-0. O sacrifício ocorreu no quinto dia. Os parâmetros avaliados incluíram força tênsil, histologia e densitometria do colágeno. Resultados: A taxa de fístula intestinal para os grupos controle e probiótico foram, respectivamente, 22,22% e 11,11% (p=0.6581). A suplementação peroperatória com probióticos aumentou a deposição de colágeno dos tipos I e III (p<0.0001), melhorou a força máxima de tração e força máxima de ruptura, p=0,0250 e p= 0,0116 respectivamente, área de fibrose (p<0.0001), e área do infiltrado inflamatório (p=0.0115). Conclusões: A utilização de probióticos impactou positivamente na qualidade da anastomose intestinal.