Brain-targeted CRISPR/Cas9 nanomedicine for effective glioblastoma therapy.

CRISPR/Cas9 gene-editing technology shows great potential for treating a variety of diseases, such as glioblastoma multiforme (GBM). However, CRISPR components suffer from inherent delivery challenges, such as poor in vivo stability of Cas9 protein and gRNA, low blood-brain barrier (BBB) permeability and non-specific tissue or cell targeting. These defects have limited the application of Cas9/gRNA ribonucleoprotein (RNP) complexes for GBM therapy. Here, we developed a brain-targeted CRISPR/Cas9 based nanomedicine by fabricating an angiopep-2 decorated, guanidinium and fluorine functionalized polymeric nanoparticle with loading Cas9/gRNA RNP for the treatment of GBM. The guanidinium and fluorine domains of our polymeric nanoparticles were both capable of interacting with Cas9/gRNA RNP to stabilize it in blood circulation, without impairing its activity. Moreover, by leveraging angiopep-2 peptide functionality, the RNP nanoparticles efficiently crossed the BBB and accumulated in brain tumors. In U87MG cells, we achieved approximately 32% gene knockout and 67% protein reduction in the targeted proto-oncogene polo-like kinase 1 (PLK1). This was sufficient to suppress tumor growth and significantly improved the median survival time of mice bearing orthotopic glioblastoma to 40 days, while inducing negligible side or off-target effects. These results suggest that the developed brain-targeted CRISPR/Cas9 based nanomedicine shows promise for effective human glioblastoma gene therapy.

Post-traumatic brain injury glioma: Characteristics, report of 2 cases report and literature review.

BACKGROUND: Traumatic brain injury (TBI) as a pathogenetic factor in glioma remains controversial, and currently there is still no clear mechanism behind post-TBI glioma. Thus, we provide two case reports of post-TBI glioma contributing power to this research, and we provide a summary of the mechanisms of post-TBI glioma through literature review. METHODS: We report two cases of brain gliomas that developed in the scar of a previous brain trauma. Both patients were male and both had suffered prior traumatic brain injuries (time interval 10-20 years), and postoperative pathological findings reported glioblastoma and WHO grade III glioma, respectively. RESULTS: These two cases further support the association of between traumatic brain injury and gliomas development. CONCLUSION: Although the epidemiological investigation between TBI and glioma is still controversial, there are still some important aspects here that can determine the possibility between TBI and gliomagenesis. Besides, we found that the reparative response of neural stem cells and the dysregulation of inflammatory cells are timportant theories of the mechanism of post-TBI glioma.

Internal Jugular Vein Fenestration and Duplication: Anatomical Findings, Prevalence, and Literature Review.

Background: Comprehensive knowledge of the internal jugular vein (IJV) regarding its anatomical variations and the pattern of its course is valuable for preventing unexpected injuries during surgical procedures or central venous access. IJV anatomical anomalies such as fenestration and duplication are rare, mainly represented by case reports, and intraoperative findings. Objective: To present two additional cases of IJV anomalies and highlight its clinical presentation, anatomical characteristics, management, and prevalence through an extensive literature review. Methods and Case Reports: From January 2017 to December 2018, we retrospectively collected data of 221 patients undergoing neck dissection (ND) procedures and identified two patients with IJV anomalies (fenestration and duplication) providing a clinical prevalence of ~0.9%. The IJV fenestration referred to an IJV bifurcation that reunites proximal to the subclavian vein, whereas in the IJV duplication both branches remain separated. In both of our cases, the spinal accessory nerve (SAN) crossed the window between the IJV branches. Conclusion: Anatomical variations are more likely to be identified intraoperatively or incidentally, and due to the risk of SAN and vascular injury, special attention should be taken to identify them preoperatively in order to reduce the risk of iatrogenic injury and unexpected complications.