Microneedle Patches Loaded with Nanovesicles for Glucose Transporter-Mediated Insulin Delivery.

Glucose-responsive insulin delivery systems that mimic insulin secretion activity in the pancreas show great potential to improve clinical therapeutic outcomes for people with type 1 and advanced type 2 diabetes. Here, we report a glucose-responsive insulin delivery microneedle (MN) array patch that is loaded with red blood cell (RBC) vesicles or liposome nanoparticles containing glucose transporters (GLUTs) bound with glucosamine-modified insulin (Glu-Insulin). In hyperglycemic conditions, high concentrations of glucose in interstitial fluid can replace Glu-Insulin via a competitive interaction with GLUT, leading to a quick release of Glu-Insulin and subsequent regulation of blood glucose (BG) levels in vivo. To prolong the effective glucose-responsive insulin release from MNs, additional free Glu-Insulin, which serves as "stored insulin", is loaded after RBC vesicles or liposome nanoparticles bound with Glu-Insulin. In the streptozotocin (STZ)-induced type 1 diabetic mouse model, this smart GLUT-based insulin patch can effectively control BG levels without causing hypoglycemia.

Expressão imunoistoquímica de GLUT-1 e marcadores de proliferação e apoptose em anomalias vasculares orais / Immunohistochemical expression of GLUT-1 and markers of proliferation and apoptosis in oral vascular anomalies

As anomalias vasculares constituem um grupo de lesões distintas, mas que podem apresentar características clínicas e histopatológicas semelhantes, que podem levar a equívocos diagnósticos.Este estudo objetivou por meio da histopatologia e da expressão imuno-histoquímica daproteína humana transportadora de glicose (GLUT1), identificar e classificar corretamente as anomalias vasculares orais, além de analisar a imunoexpressão de marcadores de proliferação e apoptose (Ki-67 e Bcl2).Todos os casos diagnosticados como "hemangiomas orais" pertencentes aos arquivos do Serviço de Anatomia Patológica da disciplina de Patologia Oral do Departamento de Odontologia (DOD) da Universidade Federal do Rio Grande do Norte (UFRN) foram revisados, totalizando 77 casos. A análise imuno-histoquímica para GLUT-1 revelou que apenas 26 (33,8%) dos espécimes tratavam-se de hemangiomas da infância (HIs) verdadeiros. Os 51 (66,2%%)espécimes GLUT-1 negativos foram então reclassificados em granulomas piogênicos (GPs) e malformações vasculares (MVs) a partir de suas características histopatológicas, totalizando 26 (33,8%) casos de HIs, 20 (26,0%) de GPs e 31 (40,2) casos de MVs orais. Os casos submetidos à análise do marcador Ki-67 apresentaram medianas diferentes HI (13,85), GP (33,70) e MV (4,55) com diferenças estatisticamente significantes entre elas (p<0,001). Em relação à proteína Bcl-2, os grupos também apresentaram diferentes medianas dos escores estabelecidos HI (1,00), GP (1,50), MVs (0,0), demonstrando diferenças estatisticamente significantes entre elas (p<0,001). Não foi observada correlação estatisticamente significante entre os índices de positividade para o Ki-67 e os escores de imunoexpressão de Bcl-2 em nenhum grupo.Dessa maneira, podemos concluir que se faz necessário uma revisão criteriosa e parametrizada dos casos de anomalias vasculares utilizando ferramentas auxiliares, como a GLUT-1, uma vez que os achados histopatológicos sozinhos, às vezes, não são suficientes para diferenciar algumas anomalias. Além disso, a análise das expressões de marcadores envolvidos nos níveis de proliferação das lesões é um aspecto importante para o melhor entendimento do seu comportamento biológico. (AU)

Vascular anomalies constitute a distinct group of lesions, but they may present similar clinical and histopatological characteristics, which can lead to diagnostic mistakes. This study aimed by histopathology and immunohistochemical expression of human glucose transporter protein (GLUT-1), correctly identify and classify oral vascular anomalies, besides analyzing the immunoexpression of markers proliferation and apoptosis (Ki-67 and Bcl-2). All cases diagnosed as "oral hemangiomas" belonging to the archives of the Service of Pathological Anatomy from the subject of Oral Pathology of the Department of Dentistry (DOD), of the Federal University of Rio Grande do Norte (UFRN) were reviewed, totalizing 77 cases. Immunohistochemical analysis for GLUT-1 showed that only 26 (33.8%) of the specimens were true infantile hemangiomas (IHs). The 51 (66.2%%) GLUT-1 negative specimens were then reclassified as pyogenic granulomas (PGs) and vascular malformations (VMs) from their histopathologic characteristics,totalizing 26 (33.8%) cases of IHs, 20 (26.0%) of PGs and 31 (40.2) cases of oral VMs. The cases analyzed by the marker Ki-67 showed different median IH (13,85), PG (33,70) and VM (4.55) with statistically significant differences between them (p <0.001). In relation to the protein Bcl-2, the groups also showed different median of the established scores IH (1.00), PG (1.50), VMs (0.0) demonstrating statistically significant differences between them (p<0,001). No statistically significant correlation between the indexes of positivity for Ki-67 and the scores of immunoexpression of Bcl-2 were observed in any group. Thus, we can conclude that it is necessary a careful and parameterized review of cases of vascular anomalies making use of auxiliary tools such as GLUT-1, since the histopathological findings alone, sometimes, are not sufficient to differentiate some anomalies. Furthermore, analysis of the expressions of markers involved in the levels of proliferation of lesions is important for a better understanding of its biological behavior aspect. (AU)