Magnetic self-assembled label-free electrochemical biosensor based on Fe3O4/α-Fe2O3 heterogeneous nanosheets for the detection of Tau proteins.

A type of electrochemical biosensors based on magnetic Fe3O4/α-Fe2O3 heterogeneous nanosheets was constructed to detect Tau proteins for early diagnosis and intervention therapy of Alzheimer's disease (AD). Firstly, Fe3O4/α-Fe2O3 heterogeneous nanosheets were fabricated as the substrate to realize magnetic self-assembly and magnetic separation to improve current response, and Fe3O4/α-Fe2O3@Au-Apt/ssDNA/MCH biosensors were successfully constructed through the reduction process of chloroauric acid, the immobilizations of aptamer (Apt) and ssDNA, and the intercept process of 6-Mercapto-1-hexanol (MCH); the construction process of the electrochemical biosensor was monitored using Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), and the factors affecting the current response of this sensor (concentration of Fe3O4/α-Fe2O3@Au and Apt/ssDNA, incubation temperature and time of Tau) were explored and optimized using differential pulse voltammetry (DPV). Analyzing the performance of this sensor under optimal conditions, the linear range was finally obtained to be 0.1 pg/mL-10 ng/mL, the limit of detection (LOD) was 0.08 pg/mL, and the limit of quantification (LOQ) was 0.28 pg/mL. The selectivity, reproducibility and stability of the biosensors were further investigated, and in a really sample analysis using human serum, the recoveries were obtained in the range of 93.93 %-107.39 %, with RSD ranging from 1.05 % to 1.94 %.

Nucleic acid aptasensor with magnetically induced self-assembly for the detection of EpCAM glycoprotein.

A "turn-on" aptasensor for label-free and cell-free EpCAM detection was constructed by employing magnetic α-Fe2O3/Fe3O4@Au nanocomposites as a matrix for signal amplification and double-stranded complex (SH-DNA/Apt probes) immobilization through Au-S binding. α-Fe2O3/Fe3O4@Au could be efficiently assembled into uniform and stable self-assembly films via magnetic-induced self-assembly technique on a magnetic glassy carbon electrode (MGCE). The effectiveness of the platform for EpCAM detection was confirmed through differential pulse voltammetry (DPV). Under optimized conditions, the platform exhibited excellent specificity for EpCAM, and a strong linear correlation was observed between the current and the logarithm of EpCAM protein concentration in the range 1 pg/mL-1000 pg/mL (R2 = 0.9964), with a limit of detection (LOD) of 0.27 pg/mL. Furthermore, the developed platform demonstrated good stability during a 14-day storage test, with fluctuations remaining below 93.33% of the initial current value. Promising results were obtained when detecting EpCAM in spiked serum samples, suggesting its potential as a point-of-care (POC) testing.

Fabrication of magneticα-Fe2O3/Fe3O4heterostructure nanorods via the urea hydrolysis-calcination process and their biocompatibility with LO2and HepG2cells.

ß-FeOOH nanorods were prepared via the urea hydrolysis process with the average length of 289.1 nm and average diameter of 61.2 nm, while magneticα-Fe2O3/Fe3O4heterostructure nanorods were prepared via the urea calcination process withß-FeOOH nanorods as precursor, and the optimum conditions were the calcination temperature of 400 °C, the calcination time of 2 h, theß-FeOOH/urea mass ratio of 1:6. The average length, diameter, and the saturation magnetization of the heterostructure nanorods prepared under the optimum conditions were 328.8 nm, 63.4 nm and 42 emu·g-1, respectively. The Prussian blue test demonstrated that the heterostructure nanorods could be taken up by HepG2 cells, and cytotoxicity tests proved that the heterostructure nanorods had no significant effect on the viabilities of LO2 and HepG2 cells within 72 h in the range of 100-1600µg·ml-1. Therefore, magneticα-Fe2O3/Fe3O4heterostructure nanorods had better biocompatibility with LO2 and HepG2 cells.

Label-free electrochemical aptasensor based on magnetic α-Fe2O3/Fe3O4 heterogeneous hollow nanorods for the detection of cancer antigen 125.

A label-free electrochemical aptasensor based on magnetic α-Fe2O3/Fe3O4 heterogeneous hollow nanorods was developed for the detection of cancer antigen 125 (CA125). Magnetic α-Fe2O3/Fe3O4 heterogeneous hollow nanorods were successfully prepared by the hydrolysis-calcination method, functionalized with polyethyleneimine (PEI), and modified with HAuCl4 to form magnetic α-Fe2O3/Fe3O4-Au nanocomposites with a layer of 5 nm gold nanoparticles (Au NPs) on the surface. The magnetic α-Fe2O3/Fe3O4-Au nanocomposites were used to fix the DNA-aptamer probe to amplify the current signal. The intensity of the current signal was proportional to the concentration of CA125, indicating that the sensor was a turn-on sensor. The linear range of the electrochemical aptasensor was 5-125 U/mL (R2 = 0.9975), and the limit of detection (LOD) was 2.99 U/mL. The electrochemical aptasensor exhibited favorable specificity, reproducibility, and stability. The analytical performance of the aptasensor in real serum samples was also investigated.

Improved biopharmaceutical performance of antipsychotic drug using lipid nanoparticles via intraperitoneal route.

This study aims to develop, characterize, and examine olanzapine-loaded solid lipid nanocarriers (OLAN-SLNs) for effective brain delivery. OLAN has poor water solubility and low penetration through blood-brain barrier (BBB). Herein, OLAN-SLNs were fabricated using high-pressure homogenization (HPH) method followed by their investigation for particle properties. Moreover, in vitro release and in vivo pharmacokinetics profiles of OLAN-SLNs were compared with pure drug. Anti-psychotic activity was performed in LPS-induced psychosis mice model. Furthermore, expressions of the COX-2 and NF-κB were measured trailed by histopathological examination. The optimized formulation demonstrated nanoparticle size (149.1 nm) with rounded morphology, negative zeta potential (-28.9 mV), lower PDI (0.334), and excellent entrapment efficiency (95%). OLAN-SLNs significantly retarded the drug release and showed sustained release pattern as compared to OLAN suspension. Significantly enhanced bioavailability (ninefold) was demonstrated in OLAN-SLNs when compared with OLAN suspension. Behavioral tests showed significantly less immobility and more struggling time in OLAN-SLNs treated mice group. Additionally, reduced expression of COX-2 and -NF κB in brain was found. Altogether, it can be concluded that SLNs have the potential to deliver active pharmaceutical ingredients to brain, most importantly to enhance their bioavailability and antipsychotic effect, as indicated for OLAN in this study.

Diverse changes in myelin protein expression in rat brain after perinatal methadone exposure.

The national incidence of neonatal abstinence syndrome has dramatically increased over the last decade due to an increase in antenatal opioid exposure. Recent human and animal studies suggest that antenatal opioid exposure impacts the developing brain. The purpose of this study is to evaluate the effects of perinatal methadone exposure on myelination in multiple regions in the developing rat brain. Pregnant Sprague-Dawley rats were randomly assigned into three experimental groups and subsequently exposed to drinking water alone or drinking water containing methadone from 7 days post coitum through day 7 or through day 19 after delivery. Two male neonatal rats were randomly selected from each litter and terminated at day 19. The cerebral cortex, hippocampus, cerebellum, and brainstem were dissected and analyzed for three myelin specific proteins - CNP, PLP, and MBP - by Western blot analysis. All pups with exposure to methadone demonstrated decreased expression of CNP, PLP, and MBP in the cerebral cortex and hippocampus. In the cerebellum, PLP expression was down­regulated without apparent alteration of CNP and MBP expression. PLP and MBP expression, but not CNP expression, were significantly inhibited in the brainstem. Compared to the pups with postnatal methadone exposure via maternal milk through day 7, partial recovery of CNP and PLP expression only occurred in the cerebral cortices of the pups exposed through day 19. The findings show that antenatal opioid exposure in rat pups is associated with regionally­specific alterations in brain myelination that diversely affects myelin proteins.

Association of serum neuron-specific enolase and bilirubin levels with cerebral dysfunction and prognosis in large-artery atherosclerotic strokes.

PURPOSE: To explore the association of serum neuron-specific enolase (NSE) and bilirubin levels with cerebral dysfunction in the prognosis of large-artery atherosclerotic (LAA) stroke cases. METHODS: This study included 73 patients who suffered from LAA stroke and were divided into experimental group (n = 41) that had an increased serum NSE and bilirubin level, and control group (n = 32). At day 1, 7, and 14, the National Institutes of Health Stroke Scale (NIHSS) score, serum NSE, and bilirubin levels were measured. The modified Rankin Scale (mRS) was used to assess neurological functional recovery at 30 days. The good outcome rate was analyzed and tested using the Kaplan-Meier product-limit method and the log-rank test one year afterwards as a follow-up. RESULTS: The NIHSS scores, serum bilirubin, and NSE levels in the experimental group were significantly increased than that of control group at days 1, 7, and 14. There was a remarkable difference in the mRS scores and the good outcome rates between the two groups. Furthermore, the computed tomography detection rate of large-area cerebral infarctions was higher in the experimental group than that of control group. CONCLUSION: High serum NSE levels and hyperbilirubinemia might be biomarkers for a poor prognosis in the early identification of LAA strokes.