Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma.

Although RNA interference (RNAi) therapy has emerged as a potential tool in cancer therapeutics, the application of RNAi to glioblastoma (GBM) remains a hurdle. Herein, to improve the therapeutic effect of RNAi on GBM, a cancer cell membrane (CCM)-disguised hypoxia-triggered RNAi nanomedicine was developed for short interfering RNA (siRNA) delivery to sensitize cells to chemotherapy and radiotherapy. Our synthesized CCM-disguised RNAi nanomedicine showed prolonged blood circulation, high BBB transcytosis and specific accumulation in GBM sites via homotypic recognition. Disruption and effective anti-GBM agents were triggered in the hypoxic region, leading to efficient tumor suppression by using phosphoglycerate kinase 1 (PGK1) silencing to enhance paclitaxel-induced chemotherapy and sensitize hypoxic GBM cells to ionizing radiation. In summary, a biomimetic intelligent RNAi nanomedicine has been developed for siRNA delivery to synergistically mediate a combined chemo/radiotherapy that presents immune-free and hypoxia-triggered properties with high survival rates for orthotopic GBM treatment.

Polymorphisms of Fatty Acid Elongase 2 Gene Afftects Risk of Pulmonary Tuberculosis in China Han Population.

BACKGROUND: As an infectious disease closely related to Mycobacterium tuberculosis, autoimmunity, inflammation, environment and heredity, the relationship between the single nucleotide polymorphism of elongase 2 gene and the susceptibility to tuberculosis is still unknown. METHODS: Between January 2016 and November 2018, a hospital-based case-control study was conducted. This epidemiological survey was conducted in both hospitals every three months. rs3798719, rs1570069, and rs2236212 in ELOVL2 gene were detected by Sanger sequencing. RESULTS: Stratified by gender, the genotypes and allele frequencies of rs3798719, rs1570069 and rs2236212 showed significant differences between the two groups (χ2 = 6.987, P = 0.030), Genetic modeling showed that rs3798719 was statistically different in the overdominance model (χ2 = 4.784, OR = 1.414, 95% CI: 1.036-1.929, P < 0.05). The polymorphism of rs2236212 between male TB patients and healthy controls was statistically different in the dominance model. (χ2 = 4.192, OR = 0.507; 95% CI: 0.262-0.981, P < 0.05). CONCLUSION: The rs3798719 of ELOVL2 gene may be associated with susceptibility to TB in female population and the rs2236212 of ELOVL2 gene may be associated with TB incidence in male patients.

Dura-splitting versus a combined technique for Chiari malformation type I complicated with syringomyelia.

BACKGROUND: Surgical approaches for Chiari malformation type I (CM-I) complicated with syringomyelia (SM) are controversial, so we assessed the efficacy and safety of two widely used procedures. METHODS: We retrospectively analyzed results from posterior fossa decompression (PFD) using bony decompression with dura-splitting or a combined technique (duraplasty with arachnoid dissection and coagulation of the herniated tonsils) for CM-I associated with SM between Jan 2008 and Feb 2016. Patients were followed up for at least one year. General data, primary outcomes (symptom improvement, syrinx reductions, and complications) and secondary outcomes (operating time, blood loss, postoperative hospital stay) for each procedure were compared. RESULTS: Of the 49 patients treated, 17 had dura-splitting decompression and 32 had the combined technique. There were no significant differences in general data. The combined technique was significantly superior to dura-splitting for long-term syrinx reductions (length, 100.03 ± 44.79 vs 72.73 ± 34.79 mm, p = 0.040; diameter, 8.09 ± 3.46 vs 5.73 ± 3.02 mm, p = 0.026) and symptom improvement (75.00% vs 47.06%, p = 0.036). No postoperative complications occurred during dura-splitting cases; however, complications occurred in 9 combined technique cases (31.25%, p = 0.010) and surgical time was longer for the combined technique (248.03 ± 60.12 vs 167.94 ± 60.11 min, p < 0.001). CONCLUSIONS: The combined technique improved long-term symptoms and reduced syringes compared to dura-splitting; however, postoperative complications are more likely.

Downregulation of phosphoglycerate kinase 1 by shRNA sensitizes U251 xenografts to radiotherapy.

Phosphoglycerate kinase 1 (PGK1) has been demonstrated to be involved in radioresistance. The present study was designed to investigate the effect of PGK1 on the radioresistance in vivo. U251 glioma cells were transfected with the short hairpin RNA (shRNA)-PGK1 and pcDNA3.1-PGK1 using Lipofectamine 2000. The radiosensitivity of U251 xenografts was observed by tumor growth curve following radiotherapy. Quantitative PCR, western blot analysis and immunohistochemistry were performed to evaluate PGK1 expression in the xenografts from the different tumor models. The expression of PGK1 was maximally inhibited in response to shRNA4 at 24 h after the transfection in vitro. Tumor growth of the U251 xenografts was significantly inhibited following treatment with shRNA-PGK1 and radiotherapy. The expression of PGK1 in vivo at the mRNA and protein levels was downregulated by the treatment of shRNA1 when compared to levels following treatment with shNC and PBS after radiotherapy. The results showed that suppression of PGK1 enhanced the radiosensitivity of U251 xenografts and suggest that PGK1 may serve as a useful target in the treatment of radioresistant glioma.

Resting-state magnetoencephalography study of "small world" characteristics and cognitive dysfunction in patients with glioma.

BACKGROUND: The purpose of this study was to analyze "small world" characteristics in glioma patients in order to understand the relationship between cognitive dysfunction and brain functional connectivity network in the resting state. METHODS: Resting-state magnetoencephalography was performed in 20 patients with glioma and 20 healthy subjects. The clustering coefficient of the resting functional connectivity network in the brain, average path length, and "small world" index (SWI) were calculated. Cognitive function was estimated by testing of attention, verbal fluency, memory, athletic ability, visual-spatial ability, and intelligence. RESULTS: Compared with healthy controls, patients with glioma showed decreased cognitive function, and diminished low and high gamma band "small world" characteristics in the resting functional connectivity network. CONCLUSION: The SWI is associated with cognitive function and is diminished in patients with glioma, and is therefore correlated with cognition dysfunction.

Over-expression of cofilin-1 and phosphoglycerate kinase 1 in astrocytomas involved in pathogenesis of radioresistance.

INTRODUCTION: Astrocytoma is among the most common intracranial tumors and radiotherapy is typically used after its resection. One of the outstanding problems encountered in the treatment is radioresistance. The lack of efficient biomarkers for evaluating the radiosensitivity of glioma precludes advances in treatment of astrocytoma and remains the most fatal cancer. METHODS: To identify potential biomarkers for assessing the radioresistance of astrocytomas, the following study investigated the proteome of astrocytoma in surgical samples from 15 typical patients. The patients were divided into 2 groups: radioresistant vs. radiosensitive (controls). Proteome was assessed using two-dimensional liquid chromatography tandem mass spectrometry (2D-LC-MS/MS). Western blot was adopted to confirm the differential expression of proteins. RESULTS: A total of 36 proteins were expressed differently between the 2 groups, represented by cofilin-1 and phosphoglycerate kinase 1 (PGK1), which up-regulated significantly in radioresistant astrocytomas though there was no obvious morphological change of tumors. Western blot analysis revealed elevated levels of protein extracts in radioresistant astrocytomas compared with the radiosensitive group. CONCLUSIONS: The results indicated cofilin-1 enhances the motility of tumor cells which is important invasive potential of malignancy. PGK1 is metabolic enzyme and seems to be correlated with the negative prognosis following radiotherapy. Thus, cofilin-1 and PGK1 might be involved in the radioresistant phenotype and are potential biomarkers for developing better therapeutic methods.