Brain Transport of Neurotoxin-I with PLA Nanoparticles through Intranasal Administration in Rats: A Microdialysis Study

National Natural Science Foundation of China [30371781]The purpose of this study was to encapsulate neurotoxin-I (NT-I) within polylactic acid (PLA) nanoparticles (NPs) and to evaluate their transport into the brain after intranasal administration (i.n.) using a microdialysis sampling technique. NT-I-NPs (NT-I radiolabeled with sodium [(125)I] iodide) were prepared and characterized. Then, NT-I-NPs were administered i.n. or i.v. to rats and the radioactivities in the olfactory bulbs were monitored for up to 240min. The nanoparticles prepared were spherical with a homogenous size distribution. The mean particle size, zeta potential and entrapment efficiency were -28.6 +/- 2.3 mV, 65 nm and 35.5 +/- 2.8%, respectively. The brain transport results showed that the time to reach the peak level (T(max)) of NT-I-NPs (i.n.) was 65 min, shorter than NT-I-NPs (i.v.) (95 min) or NT-I (i.v (145 min). The concentration at peak level (C(max)) and the total area under the concentration-time curves from zero to 411 (AUC(0-4h)) of each group followed the following order: NT-I-NPs (i.n.)>NT-I-NPs (i.v.)>NT-I (i.v.). The corresponding absolute bioavailabilities (Fabs) of NT-I-NPs (i.n.) were about 160%, 196% with NT-I-NPs (i.v) and NT-I (i.v.). as reference preparations, respectively. The brain delivery of NT-I could be enhanced with PLA nanoparticles either through i.n. or i.v. administration. Furthermore, the enhancement was more significant for i.n. than for i.v. administration. Nanoparticles as carriers would be a potential way to improve the brain transport for centrally active peptides. Copyright (C) 2008 John Wiley & Sons, Ltd

The Role and Mechanism of Borneol to Open the Blood-Brain Barrier

Background: The blood-brain barrier (BBB) is the greatest challenge in the treatment of intracranial malignant tumors. Objective: The aim of this study is to determine the role of borneol in opening the BBB and elucidate the underlying mechanisms. Materials and Methods: Twenty Sprague-Dawley (SD) rats were randomized into borneol group intragastrically administered with 10% borneol corn oil (2 mL/kg) and control group. After 30 minutes, 2% Evans blue (4 mL/kg) was injected. Thirty minutes later, brain tissue was analyzed using the Evans blue standard curve. Another 40 SD rats were randomized into high-, medium-, and low-dose borneol groups and a control group. Each rat in the experimental groups was intragastrically administered with 10% borneol corn oil (2 mL/kg, 1.25 mL/kg, and 0.5 mL/kg, respectively). The control group was injected with corn oil of 1.25 mL/kg. After 30 minutes, the rats were killed, and the brain tissues were collected. The expression of occludin, occludens-1, nitric oxide synthase, P-glycoprotein, and intercellular cell adhesion molecule-1 (ICAM-1) was detected by immunohistochemy. Results: The concentration of Evans blue in the borneol group was higher than in the control group ( P < .05). The mean density of ICAM-1 expression was higher in the experimental group than in the control group ( P < .05). In contrast, significant differences of positive area and total density of ICAM-1 were shown only between the high-dose group and the control group ( P < .05). Conclusion: Borneol can open the BBB, which might be related with the increased expression of ICAM-1

Adjuvant chemotherapy or no adjuvant chemotherapy? A prediction model for the risk stratification of recurrence or metastasis of nasopharyngeal carcinoma combining MRI radiomics with clinical factors.

BackgroundDose adjuvant chemotherapy (AC) should be offered in nasopharyngeal carcinoma (NPC) patients? Different guidelines provided the different recommendations.MethodsIn this retrospective study, a total of 140 patients were enrolled and followed for 3 years, with 24 clinical features being collected. The imaging features on the enhanced-MRI sequence were extracted by using PyRadiomics platform. The pearson correlation coefficient and the random forest was used to filter the features associated with recurrence or metastasis. A clinical-radiomics model (CRM) was constructed by the Cox multivariable analysis in training cohort, and was validated in validation cohort. All patients were divided into high- and low-risk groups through the median Rad-score of the model. The Kaplan-Meier survival curves were used to compare the 3-year recurrence or metastasis free rate (RMFR) of patients with or without AC in high- and low-groups.ResultsIn total, 960 imaging features were extracted. A CRM was constructed from nine features (seven imaging features and two clinical factors). In the training cohort, the area under curve (AUC) of CRM for 3-year RMFR was 0.872 (P ConclusionConsidering increasing RMFR, a prediction model for NPC based on two clinical factors and seven imaging features suggested the AC needs to be added to patients in the high-risk group and not in the low-risk group

Additional file 1: of MGMT promoter methylation and 1p/19q co-deletion of surgically resected pulmonary carcinoid and large-cell neuroendocrine carcinoma

Figure S1. Positive control and negative control for 1p and 19q. 1p was 52% and 19q was 66% in positive control; 1p was 5% and 19q was 3% in negative control. (JPEG 188 kb

Features extracted from targets outlined by another associate chief physician.

Features extracted from targets outlined by another associate chief physician.</p

The workflow of radiomics nomogram establishment.

a) Tumor segmentation in 3D-slicer; b) Seven types of features were extracted; c) Selection of features by pearson correlation coefficient (PCC) and random forest (RF); d) Radiomics nomogram construction and application; e) Evaluation and validation of models.</p

Comparison of AUC values between other studies and our study ROC curves.

Comparison of AUC values between other studies and our study ROC curves.</p