An Electromagnetic Steering System for Magnetic Nanoparticle Drug Delivery

Targeted delivery of pharmaceutical agents to the brain using magnetic nanoparticles (MNPs) is an efficient technique to transport molecules to disease locations. MNPs can cross the blood–brain barrier (BBB) and can be concentrated at a specific location in the brain using non-invasive electromagnetic forces. The proposed EMA consists of two coil-core system. The cores are added in the center of each coil to concentrate the flux in the region of interest. The EMA can enhance the gradient field 10 times compared to only coil system and generate the maximum magnetic field of 160 mT and 5.6 T/m. A 12-kW direct-current power supply was used to generate sufficient magnetic forces on the MNPs by regulating the input currents of the coils. Effective guidance of MNPs is demonstrated via simulations and experiments using 800-nm-diameter MNPs in a Y-shaped channel. The developed EMA system has high potentials to increase BBB crossing of MNPs for efficient drug targeting to brain region

Conditions for the differentiation of melanocyte-precursor cells from human cord blood-derived mesenchymal stem cells

The loss of skin pigmentation can induce compromised cutaneous immunity, which can result in conditions such as vitiligo. In this study, we evaluated various agents that are able to induce the differentiation of stem cells into melanocytes. We found that a mixture of forskolin (FK), stem cell factor (SCF) and endothelin-3 (EDN-3) induced melanocyte-like morphology in human cord blood-derived mesenchymal stem cells (CB-MSCs). In addition, significant expression of microphthalmia-associated transcription factor-M and tyrosinase-related protein-1 genes was observed. These results suggest that a mixture of FK, SCF and EDN-3 induces the differentiation of melanocyte-precursor cells (MPCs) from CB-MSCs.Keywords: mesenchymal stem cells, melanocyte-precursor cells, forskolin, microphthalmia-associated transcription factor-M, tyrosinase-related protein-1African Journal of Biotechnology Vol. 9(36), pp. 5975-5977, 6 September, 201

Functionalized Magnetic Force Enhances Magnetic Nanoparticle Guidance: From Simulation to Crossing of the Blood-Brain Barrier in vivo

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 study, we further investigated the effectiveness of the functionalized magnetic force with a realistic 3D 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 (DC) power supply. Our results indicate that a functionalized magnetic field can effectively prevent MNPs from sticking, and also guide them across the BBB. We used 770-nm fluorescent carboxyl MNPs in this study. Following intravenous administration of MNPs into mice, we applied an external magnetic field (EMF) to mediate transport of the MNPs across the BBB and into the brain. Furthermore, we evaluated the differential effects of functionalized magnetic fields (0.25, 0.5, and 1 Hz) and constant magnetic fields on the transport of MNPs across the BBB. Our results showed that a functionalized magnetic field is more effective than a constant magnetic field in the transport and uptake of MNPs across the BBB in mice. Specifically, applying a functionalized magnetic field with a 3 A current and 0.5 Hz frequency mediated the greatest transport and uptake of MNPs across the BBB in mic

Neuroprotection with metformin and thymoquinone against ethanol-induced apoptotic neurodegeneration in prenatal rat cortical neurons

<p>Abstract</p> <p>Background</p> <p>Exposure to ethanol during early development triggers severe neuronal death by activating multiple stress pathways and causes neurological disorders, such as fetal alcohol effects or fetal alcohol syndrome. This study investigated the effect of ethanol on intracellular events that predispose developing neurons for apoptosis via calcium-mediated signaling. Although the underlying molecular mechanisms of ethanol neurotoxicity are not completely determined, mitochondrial dysfunction, altered calcium homeostasis and apoptosis-related proteins have been implicated in ethanol neurotoxicity. The present study was designed to evaluate the neuroprotective mechanisms of metformin (Met) and thymoquinone (TQ) during ethanol toxicity in rat prenatal cortical neurons at gestational day (GD) 17.5.</p> <p>Results</p> <p>We found that Met and TQ, separately and synergistically, increased cell viability after ethanol (100 mM) exposure for 12 hours and attenuated the elevation of cytosolic free calcium [Ca²⁺]_c. Furthermore, Met and TQ maintained normal physiological mitochondrial transmembrane potential (Δψ_M), which is typically lowered by ethanol exposure. Increased cytosolic free [Ca²⁺]_cand lowered mitochondrial transmembrane potential after ethanol exposure significantly decreased the expression of a key anti-apoptotic protein (Bcl-2), increased expression of Bax, and stimulated the release of cytochrome-c from mitochondria. Met and TQ treatment inhibited the apoptotic cascade by increasing Bcl-2 expression. These compounds also repressed the activation of caspase-9 and caspase-3 and reduced the cleavage of PARP-1. Morphological conformation of cell death was assessed by TUNEL, Fluoro-Jade-B, and PI staining. These staining methods demonstrated more cell death after ethanol treatment, while Met, TQ or Met plus TQ prevented ethanol-induced apoptotic cell death.</p> <p>Conclusion</p> <p>These findings suggested that Met and TQ are strong protective agents against ethanol-induced neuronal apoptosis in primary rat cortical neurons. The collective data demonstrated that Met and TQ have the potential to ameliorate ethanol neurotoxicity and revealed a possible protective target mechanism for the damaging effects of ethanol during early brain development.</p

Functionalized Magnetic Force Enhances Magnetic Nanoparticle Guidance: From Simulation to Crossing of the Blood-Brain Barrier in vivo

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 study, we further investigated the effectiveness of the functionalized magnetic force with a realistic 3D 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 (DC) power supply. Our results indicate that a functionalized magnetic field can effectively prevent MNPs from sticking, and also guide them across the BBB. We used 770-nm fluorescent carboxyl MNPs in this study. Following intravenous administration of MNPs into mice, we applied an external magnetic field (EMF) to mediate transport of the MNPs across the BBB and into the brain. Furthermore, we evaluated the differential effects of functionalized magnetic fields (0.25, 0.5, and 1 Hz) and constant magnetic fields on the transport of MNPs across the BBB. Our results showed that a functionalized magnetic field is more effective than a constant magnetic field in the transport and uptake of MNPs across the BBB in mice. Specifically, applying a functionalized magnetic field with a 3 A current and 0.5 Hz frequency mediated the greatest transport and uptake of MNPs across the BBB in mic

Gut microbiota, its role in induction of Alzheimer’s disease pathology, and possible therapeutic interventions: Special focus on anthocyanins

The human gut is a safe environment for several microbes that are symbiotic and important for the wellbeing of human health. However, studies on gut microbiota in different animals have suggested that changes in the composition and structure of these microbes may promote gut inflammation by releasing inflammatory cytokines and lipopolysaccharides, gut-wall leakage, and may affect systemic inflammatory and immune mechanisms that are important for the normal functioning of the body. There are many factors that aid in the gut’s dysbiosis and neuroinflammation, including high stress levels, lack of sleep, fatty and processed foods, and the prolonged use of antibiotics. These neurotoxic mechanisms of dysbiosis may increase susceptibility to Alzheimer’s disease (AD) and other neurodegenerative conditions. Therefore, studies have recently been conducted to tackle AD-like conditions by specifically targeting gut microbes that need further elucidation. It was suggested that gut dyshomeostasis may be regulated by using available options, including the use of flavonoids such as anthocyanins, and restriction of the use of high-fatty-acid-containing food. In this review, we summarize the gut microbiota, factors promoting it, and possible therapeutic interventions especially focused on the therapeutic potential of natural dietary polyflavonoid anthocyanins. Our study strongly suggests that gut dysbiosis and systemic inflammation are critically involved in the development of neurodegenerative disorders, and the natural intake of these flavonoids may provide new therapeutic opportunities for preclinical or clinical studies

New microbial ecosystem created by artificak floating island

To scrutinize the microbial ecosystem and processing of water quality improvement under the artificial floating island, water quality parameteres, bacterial numbers and extracellular enzyme activities were measured biweekly flom 3, November 2001 to 20,April 2002 in Lake Paldang, Korea. Most of the mean encironmental parameters were not different from artificially floating island (AFI) site and control site. But,zooplankton numbers were about 100 times higher at AFI site than those of control site, even though the chlorophyll α concentrations were not so different. During winter, the rations of respiratory active bacteria to total bacterial number were two fold higher and enzyme activities of β-glucosidase and phosphatase were extremely higher at AFI site than those of contrl site. With these high densities of zooplankton, active bacteria and high rates of degradation under the AFI, the organic materials are eliminated at inside of lake with newly created ecosystem.Article信州大学山地水環境教育研究センター研究報告 2: 5-9(2004)departmental bulletin pape

Antioxidant and neuroprotective effects of caffeine against Alzheimer's and Parkinson's disease: insight into the role of Nrf-2 and A2AR signaling

This paper reviews the results of studies conducted on the role of caffeine in the management of different neurological disorders, such as Parkinson's disease (PD) and Alzheimer's disease (AD). To highlight the potential role of caffeine in managing different neurodegenerative diseases, we identified studies by searching PubMed, Web of Science, and Google Scholar by scrutinizing the lists of pertinent publications. According to the collected overall findings, caffeine may reduce the elevated oxidative stress; inhibit the activation of adenosine A2A, thereby regulating the accumulation of Aβ; reduce the hyperphosphorylation of tau; and reduce the accumulation of misfolded proteins, such as α-synuclein, in Alzheimer's and Parkinson's diseases. The studies have suggested that caffeine has promising protective effects against different neurodegenerative diseases and that these effects may be used to tackle the neurological diseases and/or their consequences. Here, we review the ongoing research on the role of caffeine in the management of different neurodegenerative disorders, focusing on AD and PD. The current findings suggest that caffeine produces potent antioxidant, inflammatory, and anti-apoptotic effects against different models of neurodegenerative disease, including AD, PD, and other neurodegenerative disorders. Caffeine has shown strong antagonistic effects against the adenosine A2A receptor, which is a microglial receptor, and strong agonistic effects against nuclear-related factor-2 (Nrf-2), thereby regulating the cellular homeostasis at the brain by reducing oxidative stress, neuroinflammation, regulating the accumulation of α-synuclein in PD and tau hyperphosphorylation, amyloidogenesis, and synaptic deficits in AD, which are the cardinal features of these neurodegenerative diseases

The Role of Light and Circadian Clock in Regulation of Leaf Senescence

Leaf senescence is an integrated response of the cells to develop age information and various environmental signals. Thus, some of the genes involved in the response to environmental changes are expected to regulate leaf senescence. Light acts not only as the primary source of energy for photosynthesis but also as an essential environmental cue that directly control plant growth and development including leaf senescence. The molecular mechanisms linking light signaling to leaf senescence have recently emerged, exploring the role of Phytochrome-Interacting Factors (PIFs) as a central player leading to diverse senescence responses, senescence-promoting gene regulatory networks (GRNs) involving PIFs, and structural features of transcription modules in GRNs. The circadian clock is an endogenous time-keeping system for the adaptation of organisms to changing environmental signals and coordinates developmental events throughout the life of the plant. Circadian rhythms can be reset by environmental signals, such as light-dark or temperature cycles, to match the environmental cycle. Research advances have led to the discovery of the role of core clock components as senescence regulators and their underlying signaling pathways, as well as the age-dependent shortening of the circadian clock period. These discoveries highlight the close relationship between the circadian system and leaf senescence. Key issues remain to be elucidated, including the effect of light on leaf senescence in relation to the circadian clock, and the identification of key molecules linking aging, light, and the circadian clock, and integration mechanisms of various senescence-affecting signals at the multi-regulation levels in dynamics point of view.1