RESUMEN
PURPOSE: Vitexin, an inhibitor of hypoxia-inducible factor (HIF)-1α, has anti-tumor effect. However, whether it can enhance the radiotherapy sensitization of hyperbaric oxygen (HBO) on glioma is unclear. This study aimed to investigate the effect of vitexin. METHODS: The nude mice with paw-transplanted glioma were divided into four groups: control group, HBO + radiation group, HBO + vitexin group, and HBO + vitexin + radiation group. The mice of last two groups were daily given vitexin 75 mg/kg by intraperitoneal injection. 30 min after administration of vitexin, the HBO-treated mice were daily placed in HBO chamber for 60 min. The radiation-treated mice were given local tumor irradiation once every week during the HBO treatment, and the dose of irradiation was 10 Gy/time. The experimental treatment lasted for 21 days. RESULTS: Compared with the HBO + radiation group, the tumor volume, tumor weight, and tumor weight coefficient in the HBO + vitexin + radiation group were lower (p < 0.05). Importantly, the contents of reduced glutathione and glutathione peroxidase as well as expressions of HIF-1α, vascular endothelial growth factor, glucose transporter (GLUT)-1, and GLUT-3 proteins in tumor tissues were also lower in the HBO + vitexin + radiation group than in the HBO + radiation group (p < 0.01). CONCLUSIONS: Vitexin can cooperate with HBO to sensitize the glioma radiotherapy, and its mechanisms may be correlated to the inhibition of HIF-1α protein expression and subsequent decrements of its downstream protein expressions, which finally cause the reduction of antioxidant capacity.
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Apigenina/farmacología , Glioma/radioterapia , Oxigenoterapia Hiperbárica , Tolerancia a Radiación/efectos de los fármacos , Carga Tumoral/efectos de los fármacos , Carga Tumoral/efectos de la radiación , Animales , Línea Celular Tumoral , Glioma/metabolismo , Glioma/patología , Transportador de Glucosa de Tipo 1/efectos de los fármacos , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 3/efectos de los fármacos , Transportador de Glucosa de Tipo 3/metabolismo , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Glutatión Peroxidasa/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/antagonistas & inhibidores , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The aim of this study was to investigate the effect of ozone on inflammatory cytokines in diabetic retinopathy (DR) rats. Male rats (40) weighing 300-360 g were included in this study. Thirty rats were randomly divided into the model and ozone groups after DR was induced by streptozotocin. Ten rats served as the blank group. After the diabetic models were established for one month, the rats in the ozone group were treated with 50 mg/kg ozone coloclysis for one month (three times a week). After the rats were anesthetized by intraperitoneal injection, blood samples from the abdominal aorta were collected, and the supernatant was obtained by centrifugation. Vascular endothelial growth factor (VEGF) and inflammatory cytokine content in the serum was detected by enzyme linked immunosorbent assay. The values of VEGF, intercellular cell adhesion molecule-1, interleukin-1 beta, tumor necrosis factor-a, and IL-6 were significantly different among the three groups (P < 0.05). The cytokine levels in the model group were higher than those in the blank group (P < 0.05). The level of each cytokine in the ozone group was higher than that in the blank group. Compared with the model group, the cytokine levels in the ozone group were significantly reduced (P < 0.05). Ozone had no effect on the blood glucose of diabetic rats. Treatment with ozone coloclysis may effectively reduce the secretion of VEGF and inflammatory cytokines in diabetic retinopathy rats.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/metabolismo , Ozono/farmacología , Factor A de Crecimiento Endotelial Vascular/sangre , Animales , Glucemia/metabolismo , Citocinas/sangre , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/patología , Retinopatía Diabética/sangre , Retinopatía Diabética/patología , Inflamación/metabolismo , Inflamación/patología , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
We examined the relationship between type 2 diabetes and skin wound healing. GSE38396 was downloaded from the Gene Expression Omnibus database and preprocessed using the RMA function of the Affy package. Differentially expressed genes (DEGs) were identified using the limma package, then DAVID was applied to per-form Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. MicroRNAs and their target genes were screened from the miRecords database and subjected to functional analysis. Finally, the STRING online database was applied to identify the protein-protein interaction relationships, and a combined score > 0.5 was considered to indicate an interaction. A total of 421 DEGs (208 upregulated and 213 downregulated genes) were identified in the skin lymphatic endothelial cells of patients with type II diabetes. Twenty-four microRNAs and 34 target genes were screened, including those involved in cell migration, regulation of cell proliferation, cell death, and cell adhesion regulation, among others. Protein-protein interaction network clustering analysis identified a module composed of 25 genes, and INTERPRO protein domain enrichment analysis showed that the protein domain of the clustering module main-ly contained the insulin-like growth factor binding proteins IGFBP3 and CYR61. IGFBP3 and CYR61 may play important roles in skin wound healing in diabetes patients. This information may be useful for developing methods to treat skin refractory wounds in type II diabetes.
Asunto(s)
Biología Computacional , Diabetes Mellitus Tipo 2/fisiopatología , Piel/fisiopatología , Cicatrización de Heridas , Diabetes Mellitus Tipo 2/genética , Humanos , MicroARNs/genéticaRESUMEN
OBJECTIVE: The aim of this study was to investigate whether miR-15a has prognostic relevance in human gliomas. METHODS: The expression levels of miR-15a were analyzed in glioma surgical resection tissues by microarray and quantitative real-time PCR. Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance. RESULTS: Downregulation of miR-15a was detected in most primary gliomas, which was confirmed by qRT-PCR analysis. Additionally, the down-regulation of miR-15a was significantly associated with the WHO grade (P = 0.003), the low KPS (P = 0.027), time to recurrence (P = 0.044) and the poor OS (P = 0.046). Using Kaplan-Meier analysis, a comparison of survival curves of low versus high expresser of miR-15a revealed a highly significant difference in OS (P = 0.001) and DFS (P = 0.006), which suggested that low expression of miR-15a is associated with a worse prognosis. Multivariate analyses showed that miR-15a expression was independent risk factors predicting OS [Hazard ratio (HR), 7.52; 95 % confidence interval (CI), 2.63-21.47; P = 0.002] and DFS [HR, 11.56; 95 % CI, 5.17-25.96; P < 0.001] in glioma. CONCLUSIONS: These findings indicated for the first time that the expression of miR-15a is significantly correlated with prognosis in glioma patients, suggesting that the miR-15a may serve as independent prognostic marker.