ABSTRACT
Conventional radiotherapy has a good killing effect on femoral echinococcosis. However, the sciatic nerve around the lesion is irreversibly damaged owing to bystander effects. Although intensity-modulated radiation therapy shows great advantages for precise dose distribution into lesions, it is unknown whether intensity-modulated radiation therapy can perfectly protect the surrounding sciatic nerve on the basis of good killing of femoral echinococcosis foci. Therefore, this study comparatively analyzed differences between intensity-modulated radiation therapy and conventional radiotherapy on the basis of safety to peripheral nerves. Pure-breed Meriones meridiani with bilateral femoral echinococcosis were selected as the research object. Intensity-modulated radiation therapy was used to treat left femoral echinococcosis of Meriones meridianus, while conventional radiotherapy was used to treat right femoral echinococcosis of the same Meriones meridianus. The total radiation dose was 40 Gy. To understand whether intensity-modulated radiation therapy and conventional radiotherapy can kill femoral echinococcosis, trypan blue staining was used to detect pathological changes of bone Echinococcus granulosus and protoscolex death after radiotherapy. Additionally, enzyme histochemical staining was utilized to measure acid phosphatase activity in the protoscolex after radiotherapy. One week after radiotherapy, the overall structure of echinococcosis in bilateral femurs of Meriones meridiani treated by intensity-modulated radiation therapy disappeared. There was no significant difference in the mortality rate of protoscoleces of Echinococcus granulosus between the bilateral femurs of Meriones meridiani. Moreover, there was no significant difference in acid phosphatase activity in the protoscolex of Echinococcus granulosus between bilateral femurs. To understand the injury of sciatic nerve surrounding the foci of femoral echinococcosis caused by intensity-modulated radiation therapy and conventional radiotherapy, the ultrastructure of sciatic nerves after radiotherapy was observed by transmission electron microscopy. Additionally, apoptosis of neurons was examined using a terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, and expression of Bcl-2 and Bax in sciatic nerve tissue was detected by immunohistochemical staining and western blot assay. Our results showed that most neurons in the left sciatic nerve of Meriones meridiani with echinococcosis treated by intensity-modulated radiation therapy had reversible injury, and there was no obvious apoptosis. Compared with conventional radiotherapy, the number of apoptotic cells and Bax expression in sciatic nerve treated by intensity-modulated radiation therapy were significantly decreased, while Bcl-2 expression was significantly increased. Our findings suggest that intensity-modulated radiation therapy has the same therapeutic effect on echinococcosis as conventional radiotherapy, and can reduce apoptosis of the sciatic nerve around foci caused by radiotherapy. Experiments were approved by the Animal Ethics Committee of People's Hospital of Xinjiang Uygur Autonomous Region, China (Approval No. 20130301A41) on March 1, 2013.
ABSTRACT
OBJECTIVE: The objective of this paper is to identify ego networks and pathways in rheumatoid arthritis (RA) based on EgoNet algorithm and pathway enrichment analysis. MATERIALS AND METHODS: The ego networks were identified based on the EgoNet algorithm which was comprised four steps: inputting gene expression data and protein-protein interaction data, identifying ego genes based on topological features of genes in background network, collecting ego networks by conducting snowball sampling for each ego gene, and estimating statistical significance of ego networks utilizing permutation test. To further explore the gene compositions of significant ego networks, pathway enrichment analysis was performed for each of them to investigate ego pathways in the progression of RA. RESULTS: We detected 9 ego genes from the background network, such as CREBBP, SMAD2, and YY1. Starting with each ego gene and ending with prediction accuracy dropped, a total of 9 ego networks were identified. Statistical analysis identified two significant ego networks (ego-networks 2 and 4). Ego-network 2 with ego gene SNW1 and ego-network 4 whose ego gene was YY1 both included 10 genes. The results of pathway enrichment analysis showed that signaling by NOTCH (P = 1.11E-07) and oncogene-induced senescence (P = 3.48E-04) were the two ego pathways for RA. CONCLUSION: Ego networks and pathways identified in this work might be potential therapeutic markers for RA treatment and give a hand for further studies of this disease.
