AAV-IKV mediated expression of decorin inhibits EMT and fibrosis in a murine model of Glaucoma and AAV-IKV transduction in Non-Human Primates.

Primary open angle glaucoma (POAG) and infantile aphakic glaucoma (IAG) are significant contributors of vision loss in adults and infants respectively. Both indications are associated with fibrosis of the trabecular meshwork (TM) that attenuates aqueous humor outflow, elevated intraocular pressure (IOP) and retinal ganglion cell (RGC) death. Transforming growth factor β2 (TGFβ2) is implicated in epithelial to mesenchymal transition (EMT) in both POAG and IAG.

Intravitreal AAV-IKV mediated delivery of decorin inhibits choroidal neovascularization, fibrosis, inflammation and elevates autophagy.

Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly. The exudative or wet form of AMD is caused by choroidal neovascularization (CNV) and subsequently a macular edema. Wet AMD can be effectively treated with anti-vascular endothelial growth factor (VEGF) therapies.

Cation-Cation, Cation-Anion, and Anion-Anion Translation Diffusion in Ionic Liquids─Insight from NMR Relaxometry.

H and F spin-lattice relaxation experiments have been performed for a series of ionic liquids: [HMIM][TFSI], [OMIM][TFSI], and [DMIM][TFSI] including the same anion and cations with progressively longer alkyl chains. The experiments were performed in a wide frequency range from 10 kHz to 10 MHz (referring to the H resonance frequency) versus temperature. This extensive data set has been analyzed in terms of a theoretical model including all relevant homonuclear (H-H and F-F) and heteronuclear (H-F) relaxation pathways and linking the relaxation features to the relative translational diffusion between the ion pairs (cation-cation, cation-anion, and anion-anion).

Dynamics of ionic liquid-polymer gel membranes-Insight from NMR relaxometry for [BMIM][BF4]-PVDF-HFP systems.

1H spin-lattice relaxation experiments have been performed for ionic liquid-polymer gel membranes, including 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]) and poly(vinylidene fluoride-co-hexafluoropropylene) (PVdF-HFP) with different proportions. The experiments have been performed in a broad range of resonance frequencies (from about 5 Hz to 40 MHz) vs temperature and complemented with analogous studies for [BMIM][BF4] in bulk as a reference. A model of the relaxation processes in the membranes has been proposed.

Dynamics of ionic liquids by means of nuclear magnetic resonance relaxation - overview of theoretical approaches.

This paper presents a comprehensive overview of the spin relaxation theory needed for exploring nuclear magnetic resonance (NMR) relaxometry to study the dynamical properties of ionic liquids. The term NMR relaxometry refers to relaxation experiments performed over a wide range of magnetic fields (resonance frequencies). In this way, dynamical processes occurring on timescales from milliseconds to nanoseconds can be studied, including translational and rotational dynamics of both types of ions (cations and anions).

NaZrSiPO-Polymer Composite Electrolyte for Solid State Sodium Batteries.

The integration of the flexibility of organic polymer electrolyte and high ionic conductivity of the ceramic electrolyte is attempted in search of efficient and safer battery. Composite solid polymer electrolyte (CSPE) provides high ionic conductivity with a sustainable thin film of electrolyte having the synergistic effect of ionic liquid and active inorganic filler. The CSPE is synthesized by the solution cast technique using NaZrSiPO (NZSP) as ceramic and poly(vinylidene fluoride-hexafluoropropylene) with Salt-Ionic liquid as polymer electrolyte.

Retinal Penetrating Adeno-Associated Virus.

Purpose: The most common method of delivery of genes to the outer retina uses recombinant adeno-associated virus (AAV) injected into the subretinal space using a surgical procedure. In contrast, most drugs are delivered to the retina using an intravitreal approach in an office setting. The objective of the current study was to develop AAV vectors that can reach the outer retina via intravitreal injection.

Cell-Penetrating Chaperone Nuc1 for Small- and Large-Molecule Delivery Into Retinal Cells and Tissues.

Purpose: There are currently no means available for the efficient delivery of recombinant proteins into retinal cells in vivo. Although cell-penetrating peptides have been somewhat effective in protein delivery to the retina, they generally require conjugation chemistry with the payload, negatively impacting function of the therapeutic protein. In this study, we developed a novel peptide (Nuc1) that acts as a chaperone for delivery of small and large molecules, including steroids, peptides, antibodies, recombinant proteins, and viruses (adeno-associated viruses [AAVs]) across biological membranes in vivo without the need for conjugation.

Electrochemical Performance of High-Valence Mo and Low-Valence Mn Doped- Na V (PO ) @C Cathode for Sodium-Ion Batteries.

The sodium superionic conductor (NASICON)-Na V (PO ) (NVP) is an attractive cathode for sodium-ion batteries, which is still confronted with limited rate performance due to its low electronic conductivity. In this paper, a chemical strategy is adopted to partially replace V of the NVP framework by low-valence Mn and high-valence Mo substitution. The crystal structure, sodium-ion diffusion coefficient and electrochemical performance of Mn-Mo-doped [Na V Mo Mn(PO ) @C] cathode were investigated.

Erosion-Driven Enamel Crystallite Growth Phenomenon at the Tooth Surface In Vitro.

The erosion of tooth enamel is a common oral disease. The erosion pattern and location and the effects of nanoscale chemical composition on the erosion susceptibility of enamel have been well documented. However, the enamel remineralization accompanied by erosion and its underlying physicochemical mechanisms still remain poorly understood.

Infantile Aphakic Glaucoma: A Proposed Mechanism.

Purpose: To review information pertaining to secondary glaucoma following infant lensectomy and provide evidence to support the mechanism responsible for this condition.

Methods: Reported risk factors and proposed mechanisms for infantile aphakic glaucoma are reviewed. Laboratory studies and clinical observations in affected patients with glaucoma are described.

Dynamics of Ionic Liquids in Confinement by Means of NMR Relaxometry-EMIM-FSI in a Silica Matrix as an Example.

H and F spin-lattice relaxation studies for 1-ethyl-3-methylimidazolium bis(fluorosulfonyl)imide in bulk and mesoporous MCM-41 silica matrix confinement were performed under varying temperatures in a broad range of magnetic fields, corresponding to H resonance frequency from 5Hz to 30MHz.A thorough analysis of the relaxation data revealed a three-dimensional translation diffusion of the ions in the bulk liquid and two-dimensional diffusion in the vicinity of the confining walls in the confinement. Parameters describing the translation dynamics were determined and compared.

Genotoxic Potential Assessment of the Herbicide Bispyribac-Sodium in a Fresh Water Fish Clarias batrachus (Linn.).

Genotoxic potential of herbicide bispyribac-sodium was evaluated in fish Clarias batrachus using micronucleus (MN) test and comet assay. Fish were exposed to three environmentally relevant test concentrations of the herbicide for 20, 25 and 30 days. Significant effects (p < 0.

Influence of Lanthanum Doping on Structural and Electrical/Electrochemical Properties of Double Perovskite SrCoMoO as Anode Materials for Intermediate-Temperature Solid Oxide Fuel Cells.

Lanthanum (La)-doped double perovskites SrCoMoO (SrLaCoMoO, 0.00 ≤ ≤ 0.03) were synthesized via the citrate-nitrate autocombustion route.

The role of complement membrane attack complex in dry and wet AMD - From hypothesis to clinical trials.

Data from human dry and wet age-related macular degeneration (AMD) eyes support the hypothesis that constant 'tickover' of the alternative complement pathway results in chronic deposition of the complement membrane attack complex (MAC) on the choriocapillaris and the retinal pigment epithelium (RPE). Sub-lytic levels of MAC lead to cell signaling associated with tissue remodeling and the production of cytokines and inflammatory molecules. Lytic levels of MAC lead to cell death.

G-quartet oligonucleotide mediated delivery of functional X-linked inhibitor of apoptosis protein into retinal cells following intravitreal injection.

There is currently no efficient method available for the delivery of full length functional proteins into the cytoplasm of retinal cells in vivo. Historically, the most successful approach for the treatment of retinal diseases has been intravitreal injection of antibodies or recombinant proteins, but this approach is not yet utilized for the delivery of proteins that require intracellular access for a therapeutic effect. Here we describe a platform for the delivery of functional proteins into ganglion cells, photoreceptors and retinal pigment epithelium via intravitreal injection.

Complement-Mediated Activation of the NLRP3 Inflammasome and Its Inhibition by AAV-Mediated Delivery of CD59 in a Model of Uveitis.

Uveitis is an inflammatory disorder of the eye responsible for approximately 10%-15% of blindness in the US. In this study, we examined the role of the complement membrane attack complex (MAC) and the NLRP3 inflammasome in the pathogenesis of experimental autoimmune uveitis (EAU) in normal and C9 mice that are incapable of assembling the MAC. We discovered that the MAC and the NLRP3 inflammasome and associated production of IL-1β are elevated in EAU mice and that MAC may be involved in regulation of Th1 and Th17 cell differentiation.

Dynamical properties of EMIM-SCN confined in a SiO matrix by means of H NMR relaxometry.

H nuclear magnetic resonance relaxometry is applied to investigate the translational and rotational dynamics of ionogels composed of an ionic liquid (IL): 1-ethyl-3-methyl-imidazolium-thiocyanate (EMIM-SCN) confined in a nanoporous SiO matrix. The relaxation studies were performed in the frequency range of 4 kHz-40 MHz and the temperature range of 223-248 K for different concentrations of the IL; the ratio (no. of moles of IL/no.

Reducible PEG-POD/DNA Nanoparticles for Gene Transfer In Vitro and In Vivo: Application in a Mouse Model of Age-Related Macular Degeneration.

Non-viral gene delivery systems are being developed to address limitations of viral gene delivery. Many of these non-viral systems are modeled on the properties of viruses including cell surface binding, endocytosis, endosomal escape, and nuclear targeting. Most non-viral gene transfer systems exhibit little correlation between in vitro and in vivo efficiency, hampering a systematic approach to their development.

Ninety days repeated dose oral toxicity study of in Wistar rats.

Context: is a . Since it contains two heavy metals, namely mercury and gold, it is essential to evaluate its safety. Hence, the present study was undertaken with an objective to evaluate toxicity and target organ of toxicity of if so.

Dynamics of ionic liquids in bulk and in confinement by means of (1)H NMR relaxometry - BMIM-OcSO4 in an SiO2 matrix as an example.

(1)H nuclear magnetic resonance relaxometry is applied to reveal information on the translational and rotational dynamics of the ionic liquid: 1-butyl-3-methyl imidazoliumoctyl sulfate (BMIM-OcSO4) in bulk and in a confinement formed by a nanoporous SiO2 matrix. The experimental studies were performed in a very broad frequency range, from 8 kHz to 40 MHz (referring to the (1)H resonance frequency), in order to probe motional processes at very different time scales using a single experiment, and in the temperature range of 243-303 K. The relaxation results for BMIM-OcSO4 in bulk are interpreted in terms of three relaxation contributions: a term associated with the translational dynamics of the ions (it has been assumed that the translational dynamics of cations and anions can be described by one diffusion coefficient) and two terms associated with the rotational motion of the anion and the cation, respectively.

G-quartet oligonucleotide mediated delivery of proteins into photoreceptors and retinal pigment epithelium via intravitreal injection.

There is currently no available method to efficiently deliver proteins across the plasma membrane of photoreceptor or retinal pigment epithelium (RPE) cells in vivo. Thus, current clinical application of recombinant proteins in ophthalmology is limited to the use of proteins that perform their biological function extracellularly. The ability to traverse biological membranes would enable the mobilization of a significantly larger number of proteins with previously well characterized properties.

β-Arrestin-2 Counters CXCR7-Mediated EGFR Transactivation and Proliferation.

Unlabelled: The atypical 7-transmembrane chemokine receptor, CXCR7, transactivates the EGFR leading to increased tumor growth in several tumor types. However, the molecular mechanism of CXCR7 ligand-independent EGFR transactivation is unknown. We used cDNA knock-in, RNAi and analysis of mitogenic signaling components in both normal prostate epithelial cells and prostate cancer cells to decipher the proliferation-inducing mechanism of the CXCR7-EGFR interaction.

Preparation of Self-Activated Fluorescence Mesoporous Silica Hollow Nanoellipsoids for Theranostics.

The newly developed multifunctional (self-activated fluorescent, mesoporous, and biocompatible) hollow mesoporous silica nanoellipsoids (f-hMS) are potentially useful as a delivery system of drugs for therapeutics and imaging purposes. For the synthesis of f-hMS, self-activated fluorescence hydroxyapatite (fHA) was used as a core template. A mesoporous silica shell was obtained by silica formation and subsequent removal of the fHA core, which resulted in a hollow-cored f-hMS.