Multiple sclerosis is a disease caused by autoantigen-responsive immune cells that disrupt the myelin in the central nervous system (CNS). Although immunosuppressive drugs are used to suppress ...symptoms, no definitive therapy exists. As in the experimental autoimmune encephalitis (EAE) model of multiple sclerosis, a partial sequence of the myelin oligodendrocyte glycoprotein (MOG35–55) was identified as a causative autoantigen. This suggests that the induction of immune tolerance that is specific to MOG35–55 would be a fundamental treatment for EAE. We previously reported that lipid nanoparticles (LNPs) containing an anionic phospholipid, phosphatidylserine (PS), in their lipid composition, can be used to deliver mRNA and that this leads to proteins of interest to be expressed in the spleen. In addition to the targeting capability of PS, PS molecules avoid activating the immune system. Physiologically, the recognition of PS on apoptotic cells suppresses immune activation against these cells by releasing cytokines, such as interleukin-10 (IL-10) and transforming growth factor (TGF)-β that negatively regulate immunity. In this study, we tested whether mRNA delivery of autoantigens to the spleen by PS-LNPs causes the expression of MOG35–55 antigens with minimal immune stimulation and whether this could be used to treat an EAE model by inducing immune tolerance.
The blood–brain barrier (BBB), which is comprised of brain capillary endothelial cells, plays a pivotal role in the transport of drugs from the blood to the brain. Therefore, an analysis of proteins ...in the endothelial cells, such as transporters and tight junction proteins, which contribute to BBB function, is important for the development of therapeutics for the treatment of brain diseases. However, gene transfection into the vascular endothelial cells of the BBB is fraught with difficulties, even in vitro. We report herein on the development of lipid nanoparticles (LNPs), in which mRNA is encapsulated in a nano-sized capsule composed of a pH-activated and reductive environment-responsive lipid-like material (ssPalm). We evaluated the efficiency of mRNA delivery into non-polarized human brain capillary endothelial cells, hCMEC/D3 cells. The ssPalm LNPs permitted marker genes (GFP) to be transferred into nearly 100% of the cells, with low toxicity in higher concentration. A proteomic analysis indicated that the ssPalm-LNP had less effect on global cell signaling pathways than a Lipofectamine MessengerMAX/GFP-encoding mRNA complex (LFN), a commercially available transfection reagent, even at higher mRNA concentrations.
Abstract
In this study, the performance of a paper-based, screen-printed biofuel cell with mesoporous MgO-templated carbon (MgOC) electrodes was improved in two steps. First, a small amount of ...carboxymethyl cellulose (CMC) was added to the MgOC ink. Next, the cathode was modified with bilirubin prior to immobilizing the bilirubin oxidase (BOD). The CMC increased the accessibility of the mesopores of the MgOC, and subsequently, the performance of both the bioanode and biocathode. CMC also likely increased the stability of the electrodes. The pre-modification with bilirubin improved the orientation of the BOD, which facilitated direct electron transfer. With these two steps, an open circuit potential of 0.65 V, a maximal current density of 1.94 mA cm
−2
, and a maximal power density of 465 μW cm
−2
was achieved with lactate oxidase as bioanode enzyme and lactate as fuel. This is one of the highest reported performances for a biofuel cell.
•ZnO thin films are deposited in atmospheric pressure by spray pyrolysis.•ZnO thin films deposited over 50°C are the hexagonal wurtzite structure.•The deference between the grain density and the ...overall density is discussed.•ZnO thin film deposited at 150°C has the quality near ZnO single crystal.
Non-doped ZnO thin films are deposited on glass substrates by spray pyrolysis using diethylzinc solution at a range from a room temperature to 150°C while making N2 gas flow in atmospheric pressure. The morphology, the structural property, the density and the optical band gap are studied. As the deposition temperature is increasing, the overall density and the optical band gap approach to the values of ZnO single crystal. The quality of ZnO thin film deposited at 150°C becomes near ZnO single crystal.
Non‐doped ZnO thin films are deposited on glass by spray pyrolysis using Diethylzinc diluted with diisopropyl ether. The droplet impacts are observed and the structural properties of films are ...studied as deposition temperature dependence. The shape of a droplet impacts changes from a hemisphere to a flat plane with increasing the deposition temperature. The images of cross sectional transmittance electron microscopy show granular non‐crystalline for RT (room temperature) sample and columnar polycrystalline for 150 °C sample as shown on the right‐side. The growth mechanism of ZnO thin films is discussed by considering the relationship between the shape of droplet impacts and the morphology of the deposited films. Also, the presence of the crystal formed by precursor is suggested for the films deposited at lower temperature.
Cross sectional TEM images of deposited films. Deposition temperature: (a) RT, (b) 150 °C.
