RESUMO
Diabetic neuropathic pain (DNP) is the most common disabling complication of diabetes. Emerging evidence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area; however, the underlying molecular events remain poorly understood. Here we found that an axon guidance molecule, Netrin-3 (Ntn-3), was expressed in the sensory neurons of mouse dorsal root ganglia (DRGs), and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model. Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice. In contrast, the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice. In conclusion, our studies identified Ntn-3 as an important regulator of DNP pathogenesis by gating the aberrant sprouting of sensory axons, indicating that Ntn-3 is a potential druggable target for DNP treatment.
Assuntos
Camundongos , Animais , Diabetes Mellitus Experimental/metabolismo , Axônios/fisiologia , Neuropatias Diabéticas , Células Receptoras Sensoriais/metabolismo , Neuralgia/metabolismoRESUMO
Most viruses have RNA genomes, their biological functions are expressed more by folded architecture than by sequence
Among the various RNA structures, pseudoknots are the most typical. In general, RNA secondary structures prediction doesn't contain pseudoknots because of its difficulty in modeling
Here we present an algorithm of dynamic matching to predict RNA secondary structures with pseudoknots by combining the merits of comparative and thermodynamic approaches
We have tested and verified our algorithm on some viral RNA
Comparisons show that our algorithm and loop matching method has similar accuracy and time complexity, and are more sensitive than the maximum weighted matching method and Rivas algorithm. Among the four methods, our algorithm has the best prediction specificity. The results show that our algorithm is more reliable and efficient than the other methods