Objective This study is to identify long-term functional recovery and maturity of regenerated nerve fibers after repairing mouse nerve defects with chitosan/polylactide-co-polyglycolide artificial nerve grafts ( CPANGs ) . Methods Mouse sciatic nerve defects, 2mm in length, were bridged by CPANGs (n=6), with nerve autograft (n=6) and nerve defect (n=6) as controls.Plantar test, electrophysiological examination and laser Doppler perfusion imaging following nerve crush were carried out at 1 year after repair to assess nerve function recovery , while muscle wet weight ratio, histological assessment and transmission electron microscopy were performed to evaluate nerve re -innervation and maturity of regenerated nerve fibers .Results When compared to the autograft group , the CPANG group did not show statistically significant difference in functional recovery in terms of paw withdrawal latency , neurogenic vasodilatation , amplitude and latency of compound muscle action potentials ( CMAPs ) , wet weight ratio of gastrocnemius and tibialis cranialis muscles , number of myelinated nerve fibers and density of unmyelinated axons .However , both these two repair groups exhibited significantly longer CMAPs latency , thinner myelin sheath and a lag-behind shift of diameter distribution of myelinated axons as compared to the normal control .Conclusion At 1 year after the mouse sciatic nerve defect was repaired by CPANGs , sensory and autonomic nerve function , number of regenerated axons and muscle re-innervation degree were recovered to the same extent as nerve autografting , but the regenerated nerve fibers were in a state of immaturity .

Arisaema heterophyllum Blume is one of the three medicinal plants known as traditional Chinese medicine Rhizoma Arisaematis (RA). RA has been popularly used to treat patients with convulsions, inflammation, and cancer for a long time. However, the underlying mechanisms for RA effects are still unclear. The present study was designed to determine the cytotoxicity of agglutinin isolated from Arisema heterophyllum Blume (AHA) and explore the possible mechanisms in human non-small-cell lung cancer A549 cells. AHA with purity up to 95% was isolated and purified from Arisaema heterophyllum Blume using hydrophobic interaction chromatography. AHA dose-dependently inhibited the proliferation of A549 cells and induced G phase cell cycle arrest. AHA induced apoptosis by up-regulating pro-apoptotic Bax, decreasing anti-apoptotic Bcl-2, and activating caspase-9 and caspase-3. In A549 cells treated with AHA, the PI3K/Akt pathway was inhibited. Furthermore, AHA induced increase in the levels of ER stress markers such as phosphorylated eukaryotic initiation factor 2α (p-eIF2α), C/EBP-homologous protein (CHOP), inositol-requiring enzyme 1α (IRE1α), and phosphorylated c-Jun NH-terminal kinase (p-JNK). AHA also induced autophagy in A549 cells. Staining of acidic vesicular organelles (AVOs) and increase in the levels of LC3II and ATG7 were observed in AHA-treated cells. These findings suggested that AHA might be one of the active components with anti-cancer effects in Arisaema heterophyllum Blume. In conclusion, cytotoxicity of AHA on cancer cells might be related to its effects on apoptosis and autophagy through inhibition of PI3K/Akt pathway and induction of ER stress.
A549 Cells ; Agglutinins ; pharmacology ; Apoptosis ; drug effects ; Arisaema ; chemistry ; Autophagy ; drug effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; enzymology ; metabolism ; physiopathology ; Cell Line, Tumor ; Drugs, Chinese Herbal ; pharmacology ; Endoplasmic Reticulum Stress ; drug effects ; Humans ; MAP Kinase Signaling System ; drug effects ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Phosphorylation ; drug effects ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism