Bioengineered Zinc Oxide Nanoparticle-Loaded Hydrogel for Combinative Treatment of Spinal Cord Transection.

Spinal cord injury (SCI) is one of the most destructive diseases. The neuroinflammation microenvironment needs comprehensive mitigation of damages. Thus, regulation of local, microenvironment drugs could be a potential effective treatment. However, clinical studies on SCI with common treatment have reported it to cause systemic toxicity and side effects. Zinc oxide nanoparticles (ZnONPs) have been widely reported to have satisfying anti-inflammation function. Furthermore, green synthesis procedures can improve the capability and possible utilization of ZnONPs. However, the efficient administration and underlying mechanism of ZnONPs in SCI treatment remain unclear. Herein, an innovative approach was built by utilizing ZnONPs loaded in a skeletal muscle-derived adhesive hydrogel (ZnONPs-Gel). Different from the systemic application of ZnONPs, the local administration of ZnONPs-Gel offered the ZnONPs-loaded extracellular matrix with beneficial biocompatibility to the injured spinal cord, thereby promoting effective function recovery. Mechanistically, the ZnONPs-Gel treatment not only markedly reduced ROS production but also decreased apoptosis in the injured spinal cord. Therefore, the strategy based on local administration of the ZnONPs-Gel in the early stage of SCI may be an effective therapeutic treatment.

BTG1 might be employed as a biomarker for carcinogenesis and a target for gene therapy in colorectal cancers.

Here, BTG1 overexpression inhibited proliferation, induced differentiation, autophagy, and apoptosis in colorectal cancer cells (p<0.05). BTG1 overexpression reduced mitochondrial membrane potential and caused senescence in HCT-116 transfectants (p<0.05). BTG1-induced G2 arrest might be related to Cyclin B1 and Cdc25B hypoexpression in HCT-15 transfectants, while G1 arrest in HCT-116 transfectants overexpressing p21 and p27. BTG1 overexpression decreased the expression of Bcl-2, Bcl-xL, XIAP, Akt1 or survivin and increased the expression of Bax or p53 in colorectal cancer cells. BTG1-induced autophagy was dependent on Beclin-1 expression. BTG1 overexpression might weaken ß-catenin pathway in colorectal cancer cells. The chemosensitivity of BTG1 transfectants to paclitaxel, cisplatin, MG132 or SAHA was positively correlated with its apoptotic induction. There was a lower expression level of BTG1 in cancer than matched non-neoplastic mucosa by RT-PCR (p<0.05), while versa for Western blot and immunohistochemical data (p<0.05). BTG1 overexpression significantly suppressed the growth of HCT-15 and HCT-116 via inhibiting proliferation, inducing apoptosis and autophagy in nude mice. Up-regulated BTG1 expression plays an important role in colorectal carcinogenesis as a potential biomarker. BTG1 expression might reverse aggressive phenotypes, so it might be employed as a target of gene therapy for colorectal cancer.

Methylprednisolone exerts neuroprotective effects by regulating autophagy and apoptosis.

Methylprednisolone markedly reduces autophagy and apoptosis after secondary spinal cord injury. Here, we investigated whether pretreatment of cells with methylprednisolone would protect neuron-like cells from subsequent oxidative damage via suppression of autophagy and apoptosis. Cultured N2a cells were pretreated with 10 µM methylprednisolone for 30 minutes, then exposed to 100 µM H2O2 for 24 hours. Inverted phase contrast microscope images, MTT assay, flow cytometry and western blot results showed that, compared to cells exposed to 100 µM H2O2 alone, cells pretreated with methylprednisolone had a significantly lower percentage of apoptotic cells, maintained a healthy morphology, and showed downregulation of autophagic protein light chain 3B and Beclin-1 protein expression. These findings indicate that methylprednisolone exerted neuroprotective effects against oxidative damage by suppressing autophagy and apoptosis.