Systematic tracking of altered modules identifies disrupted pathways in teratozoospermia.

The objective of this study was to identify disrupted pathways in teratozoospermia by systematically tracking dysregulated modules in reweighted protein-protein interaction (PPI) networks. We inferred and reweighted the PPI networks of normal and teratozoospermia groups based on Spearman correlation coefficients. Modules in the PPI networks were explored via a clique-merging algorithm and altered modules were identified based on maximum weight bipartite matching. Furthermore, pathway-enrichment analyses of genes in altered modules were performed by Database for Annotation, Visualization, and Integrated Discovery (DAVID) to illuminate the biological pathways in teratozoospermia. A total of 20,102 genes were screened from the expression profile. We explored 2406 and 2101 modules in normal and disease PPI networks, respectively. Moreover, we obtained 875 altered modules by comparing modules in normal and teratozoospermia PPI networks. At P < 0.01, the genes involved in 2855 interactions with score changes >1 were mainly enriched in 66 pathways and the genes in altered modules were enriched in 71 pathways. The activity genes (missed and added genes in the disrupted modules) were enriched in 41 common pathways. There were 36 mutual enriched pathways under the five different conditions. Moreover, the cell cycle pathway was disrupted in the first 10 pathways of each condition. This study provides a powerful biomarker discovery platform to better understand the progression of teratozoospermia by systematically tracking dysregulated modules. This method uncovered potential diagnostic and therapeutic targets of teratozoospermia. This information might lead to improved monitoring and treatment of teratozoospermia.

Effect of lentivirus-mediated RNA interference of APC-Cdh1 expression on spinal cord injury in rats.

This study investigated cadherin-1 (Cdh1) expression in the sensorimotor cortex of rats after spinal cord injury (SCI). The repairing effect of Cdh1 was evaluated by silencing its expression with lentivirus-mediated RNAi. Twenty male Sprague-Dawley (SD) rats were randomly divided into a normal group and an operation group. Rats of the operation group were given SCI by the Allen method (T10-T11). Cdh1 expression in the sensorimotor cortex was examined by quantitative real-time polymerase chain reaction (PCR) and Western blot analysis. Thirty male SD rats were divided into a sham-operation (SO) group, a lentivirus vector (LV) group, and a recombinant lentivirus (RL) group. Rat behavior was evaluated using the Basso-Beattie-Bresnahan (BBB) test every week. Ten days after injection, Cdh1 expression was examined by quantitative real-time PCR and Western blot. Six weeks after injury, animals were injected with biotinylated dextran amine-Texas Red (BDA-TR), and then at 8 weeks, spinal cords were removed and sectioned in serial order. The expression of Cdh1 mRNA was significantly higher in the operation than in the normal group (P < 0.05). The expression of Cdh1 mRNA was lower in the RL than in the SO or LV groups at 10 days after injection (P < 0.05). In addition, the BBB score was higher for the RL than for the SO or LV groups at 6 weeks after injury (P < 0.05). A novel population of BDA-labeled axons was observed extending past the lesion in the RL group, which was rarely observed in the SO and LV groups. These results suggest that the anaphase-promoting complex-Cdh1 may play an important role in inhibiting axonal growth.