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In recent studies, we introduced the concept of functionalized magnetic force as a method to prevent nanoparticles from sticking to vessel walls caused by extensive simulation and in vitro experiments involving a Y-shaped channel. In this paper, we further investigated the effectiveness of the functionalized magnetic force with a realistic 3-D vessel through simulations. For the simulations, we considered a more realistic continuous injection of particles with different magnetic forces and frequencies. Based on the results from our simulation studies, we performed in vivo mice experiments to evaluate the effectiveness of using a functionalized magnetic force to aid magnetic nanoparticles (MNPs) in crossing the blood–brain barrier (BBB). To implement the functionalized magnetic force, we developed an electromagnetic actuator regulated by a programmable direct current power supply. Our results indicate that a functionalized magnetic field (FMF) can effectively prevent MNPs from sticking, and also guide them across the BBB. We used 770 nm fluorescent carboxyl MNPs in this paper. Following intravenous administration of MNPs into mice, we applied an external magnetic field to mediate transport of the MNPs across the BBB and into the brain. Furthermore, we evaluated the differential effects of FMFs (0.25, 0.5, and 1 Hz) and constant magnetic fields (CMFs) on the transport of MNPs across the BBB. Our results showed that an FMF is more effective than a CMF in the transport and uptake of MNPs across the BBB in mice. In particular, applying an FMF with a 3 A current and 0.5 Hz frequency mediated the greatest transport and uptake of MNPs across the BBB in mice. [ABSTRACT FROM PUBLISHER]

Here we investigated for the first time the inhibitory potential of Glycine (Gly) against ethanol-induced oxidative stress, neuroinflammation and apoptotic neurodegeneration in human neuroblastoma SH-SY5Y cells and in the developing rat brain. The Gly co-treatment significantly increased the cell viability, inhibited the expression of phospho-Nuclear Factor kappa B (p-NF-kB) and caspase-3 and reduced the oxidative stress in ethanol-treated SH-SY5Y cells in a PI3K-dependent manner. Seven days old male rat pups were injected with ethanol (5 g/kg subcutaneously, prepared in a 20% saline solution) and Gly (1 g/kg). Gly co-treatment stimulated the PI3K/Akt signaling pathway to limit the ethanol induced reactive oxygen species (ROS) production in the developing rat brain. It lowered the ethanol-elevated levels of phospho-c Jun N terminal kinase (p-JNK) and its various downstream apoptotic markers, including Bax, cytochrome C, caspase-3 and PARP-1. Additionally, the Gly treatment upregulated antiapoptotic Bcl-2 proteins and prevented ethanol-induced neurodegeneration as assessed by Fluoro-Jade-B (FJB) and Nissl staining. Furthermore, the Gly administration caused significant reduction in the ethanol-induced neuroinflammation by inhibiting the expression of inflammatory markers such as p-NF- k B, cyclooxygenase 2 (COX2) and tumor necrosis factor-α (TNF-α) and reversed the ethanol-induced synaptic protein markers expression. The results suggest that acute Gly treatment reduces ethanol-induced oxidative stress and neuronal cell loss in SH-SY5Y cells and in the developing rat brain. Therefore, Gly may be considered as potential treatment in ethanol-intoxicated newborns and infants. [ABSTRACT FROM AUTHOR]

Increasing evidence demonstrates that β-amyloid (Aβ) elicits oxidative stress, which contributes to the pathogenesis and disease progression of Alzheimer's disease (AD). The aims of the present study were to determine and explore the antioxidant nature and potential mechanism of vanillic acid (VA) in Aβ1-42-induced oxidative stress and neuroinflammation mediated cognitive impairment in mice. An intracerebroventricular (i.c.v.) injection of Aβ1-42 into the mouse brain triggered increased reactive oxygen species (ROS) levels, neuroinflammation, synaptic deficits, memory impairment, and neurodegeneration. In contrast, the i.p. (intraperitoneal) administration of VA (30 mg/kg, for 3 weeks) after Aβ1-42-injection enhanced glutathione levels (GSH) and abrogated ROS generation accompanied by an induction of the endogenous nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) via the activation of Akt and glycogen synthase kinase 3β (GSK-3β) in the brain mice. Additionally, VA treatment decreased Aβ1-42-induced neuronal apoptosis and neuroinflammation and improved synaptic and cognitive deficits. Moreover, VA was nontoxic to HT22 cells and increased cell viability after Aβ1-42 exposure. To our knowledge, this study is the first to reveal the neuroprotective effect of VA against Aβ1-42-induced neurotoxicity. Our findings demonstrate that VA could potentially serve as a novel, promising, and accessible neuroprotective agent against progressive neurodegenerative diseases such as AD. [ABSTRACT FROM AUTHOR]

The blood--brain barrier (BBB) hinders drug delivery to the brain. Despite various efforts to develop preprogramed actuation schemes for magnetic drug delivery, the unmodeled aggregation phenomenon limits drug delivery performance. This paper proposes a novel scheme with an aggregation model for a feed-forward magnetic actuation design. A simulation platform for aggregated particle delivery is developed and an actuation scheme is proposed to deliver aggregated magnetic nanoparticles (MNPs) using a discontinuous asymmetrical magnetic actuation. The experimental results with a Y-shaped channel indicated the success of the proposed scheme in steering and disaggregation. The delivery performance of the developed scheme was examined using a realistic, three-dimensional (3D) vessel simulation. Furthermore, the proposed scheme enhanced the transport and uptake of MNPs across the BBB in mice. The scheme presented here facilitates the passage of particles across the BBB to the brain using an electromagnetic actuation scheme. [ABSTRACT FROM AUTHOR]

Magnetic-guided targeted drug delivery (TDD) systems can enhance the treatment of diverse diseases. Despite the potential and promising results of nanoparticles, aggregation prevents precise particle guidance in the vasculature. In this study, we developed a simulation platform to investigate aggregation during steering of nanoparticles using a magnetic field function. The magnetic field function (MFF) comprises a positive and negative pulsed magnetic field generated by electromagnetic coils, which prevents adherence of particles to the vessel wall during magnetic guidance. A commonly used Y-shaped vessel was simulated and the performance of the MFF analyzed; the experimental data were in agreement with the simulation results. Moreover, the effects of various parameters on magnetic guidance were evaluated and the most influential identified. The simulation results presented herein will facilitate more precise guidance of nanoparticles in vivo. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa (P. aeruginosa) is an aerobic gram-negative, non-spore forming, rod-shaped bacterium. It accelerates the decline in lung function and ultimately leads to increased mortality and morbidity rate. Survival and virulence of P. aeruginosa is due to its biofilm formation ability. The main aim of this study was to test the synergistic effect of silver nanoparticles (AgNPs) in combination with Polymyxin B against biofilms of P. aeruginosa. A total of 500 pus aspirations were collected and bacterial pathogens were identified. Biofilm formation was attained using a glass tube method and microtiter plate assay. The minimum inhibitory concentration of Polymyxin B was determined using agar well diffusion method. Silver nanoparticles were synthesized by chemical reduction method followed by determination of their anti-pseudomonal ability separately and in combination with Polymyxin B using microtiter plate assay. Our results showed that 120 out of 500 samples were Pseudomonas positive. The ratio of multidrug-resistant (MDR) in our collected Pseudomonas samples was 83% (25/30). Generally, the minimum inhibitory concentration (MIC) of Polymyxin B was 16 µg/mL and that of AgNPs was null. However, AgNPs showed great synergistic effect in combination with Polymyxin B. Synergistically, the efficacy of Polymyxin B was enhanced four times as compared to unaided Polymyxin B. [ABSTRACT FROM AUTHOR]

Aims Lipopolysaccharide ( LPS) induces oxidative stress and neuroinflammation both in vivo and in vitro. Here, we provided the first detailed description of the mechanism of melatonin neuroprotection against LPS-induced oxidative stress, acute neuroinflammation, and neurodegeneration in the hippocampal dentate gyrus (DG) region of the postnatal day 7 ( PND7) rat brain. Methods The neuroprotective effects of melatonin against LPS-induced neurotoxicity were analyzed using multiple research techniques, including Western blotting, immunofluorescence, and enzyme-linked immunosorbent assays ( ELISAs) in PND7 rat brain homogenates and BV2 cell lysates in vitro. We also used EX527 to inhibit silent information regulator transcript-1 ( SIRT1). Results A single intraperitoneal (i.p) injection of LPS to PND7 rats significantly induced glial cell activation, acute neuroinflammation, reactive oxygen species ( ROS) production and apoptotic neurodegeneration in hippocampal DG region after 4 h. However, the coadministration of melatonin significantly inhibited both LPS-induced acute neuroinflammation and apoptotic neurodegeneration and improved synaptic dysfunction in the hippocampal DG region of PND7 rats. Most importantly, melatonin stimulated the SIRT1/Nrf2 (nuclear factor-erythroid 2-related factor 2) signaling pathway to reduce LPS-induced ROS generation. The beneficial effects of melatonin were further confirmed in LPS-stimulated BV2 microglia cell lines in vitro using EX527 as an inhibitor of SIRT1. LPS-induced oxidative stress, Nrf2 inhibition, and neuroinflammation are SIRT1-dependent in BV2 microglia cell lines. Conclusion These results demonstrated that melatonin treatment rescued the hippocampal DG region of PND7 rat brains against LPS-induced oxidative stress damage, acute neuroinflammation, and apoptotic neurodegeneration via SIRT1/Nrf2 signaling pathway activation. [ABSTRACT FROM AUTHOR]