Therapeutic effects of pyrrolidine dithiocarbamate on acute lung injury in rabbits

<p>Abstract</p> <p>Background</p> <p>Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is an early characteristic of multiple organ dysfunction, responsible for high mortality and poor prognosis in patients. The present study aims to evaluate therapeutic effects and mechanisms of pyrrolidine dithiocarbamate (PDTC) on ALI.</p> <p>Methods</p> <p>Alveolar-arterial oxygen difference, lung tissue edema and compromise, NF-κB activation in polymorphonuclear neutrophil (PMN), and systemic levels of tumor necrosis factor-alpha (TNFa) and intercellular adhesion molecule-1 (ICAM-1) in rabbits induced by the intravenous administration of lipopolysaccharide (LPS) and treated with PDTC. Production of TNFa and IL-8, activation of Cathepsin G, and PMNs adhesion were also measured.</p> <p>Results</p> <p>The intravenous administration of PDTC had partial therapeutic effects on endotoxemia-induced lung tissue edema and damage, neutrophil influx to the lung, alveolar-capillary barrier dysfunction, and high systemic levels of TNFa and ICAM-1 as well as over-activation of NF-κB. PDTC could directly and partially inhibit LPS-induced TNFa hyper-production and over-activities of Cathepsin G. Such inhibitory effects of PDTC were related to the various stimuli and enhanced through combination with PI3K inhibitor.</p> <p>Conclusion</p> <p>NF-κB signal pathway could be one of targeting molecules and the combination with other signal pathway inhibitors may be an alternative of therapeutic strategies for ALI/ARDS.</p

Reorganization Energy for Internal Electron Transfer in Multicopper Oxidases.

We have calculated the reorganization energy for the intramolecular electron transfer between the reduced type 1 copper site and the peroxy intermediate of the trinuclear cluster in the multicopper oxidase CueO. The calculations are performed at the combined quantum mechanics and molecular mechanics (QM/MM) level, based on molecular dynamics simulations with tailored potentials for the two copper sites. We obtain a reorganization energy of 91-133 kJ/mol, depending on the theoretical treatment. The two Cu sites contribute by 12 and 22 kJ/mol to this energy, whereas the solvent contribution is 34 kJ/mol. The rest comes from the protein, involving small contributions from many residues. We have also estimated the energy difference between the two electron-transfer states and show that the reduction of the peroxy intermediate is exergonic by 43-87 kJ/mol, depending on the theoretical method. Both the solvent and the protein contribute to this energy difference, especially charged residues close to the two Cu sites. We compare these estimates with energies obtained from QM/MM optimizations and QM calculations in a vacuum and discuss differences between the results obtained at various levels of theory

Catalytic Cycle of Multicopper Oxidases Studied by Combined Quantum- and Molecular-Mechanical Free-Energy Perturbation Methods

We have used combined quantum mechanical and molecular mechanical free-energy perturbation methods in combination with explicit solvent simulations to study the reaction mechanism of the multicopper oxidases, in particular the regeneration of the reduced state from the native intermediate. For 52 putative states of the trinuclear copper cluster, differing in the oxidation states of the copper ions and the protonation states of water- and O2-derived ligands, we have studied redox potentials, acidity constants, isomerisation reactions, as well as water- and O2 binding reactions. Thereby, we can propose a full reaction mechanism of the multicopper oxidases with atomic detail. We also show that the two copper sites in the protein communicate so that redox potentials and acidity constants of one site are affected by up to 0.2 V or 3 pKa units by a change in the oxidation state of the other site

The psychology and policy of overcoming economic inequality

Data and materials’ availability: All data are publicly available for the survey data used (https://osf.io/njd62/) and from the UN Gender Inequality Index (https://hdr.undp.org/data-center/documentation-and-downloads). Financial transaction data were provided through an agreement with Columbia Business School.Recent arguments claim that behavioral science has focused – to its detriment – on the individual over the system when construing behavioral interventions. In this commentary, we argue that tackling economic inequality using both framings in tandem is invaluable. By studying individuals who have overcome inequality, “positive deviants,” and the system limitations they navigate, we offer potentially greater policy solutions.This research was supported in part by the National Science Foundation (no. 2218595) and by Undergraduate Global Engagement at Columbia University. Additional support was provided to individual researchers from the Columbia University Office of the Provost, Masaryk University Centre for International Cooperation, and the Benjamin A. Gilman International Fund from the United States Department of State

Codeposition of Fe 3 O 4 nanoparticles sandwiched between g-C3N4 and TiO2 nanosheets: Structure, characterization and high photocatalytic activity for efficiently degradation of dye pollutants

Novel ternary nanocomposite photocatalysts based on g-C3N4 /Fe3O4 /TiO2 nanosheet were synthesized using simple solid combustion, hydrothermal and wetness impregnation methods. The g-C3N4 nanosheet (2D)/ Fe3O4 /TiO2 nanosheet (2D) triad-interface nanocomposite arranged in the form of Fe 3 O 4 nanoparticle was sandwiched and effectively dispersed on the surface between g-C3N4 and TiO2 nanosheets. The synthesized composites were characterized by some specific techniques such as X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, field emission scanning electronic microscopy (FE-SEM), transmission electron microscope (TEM), vibrating sample magnetometer (VSM), specific surface area (SSA), and dynamic laser scattering (DLS) analyzer. The effect of Fe3O4 loading quantity on photocatalytic overall performance indicated that g-C3N4 nanosheets/Fe3O4/TiO2 nanosheets with 5% wt Fe3O4 nanoparticle exhibit the best photocatalytic ability. These composites showed excellent activities in the UV-light-driven degradation of direct blue (DB), methyl blue (MB) and safranin (SA). After irradiation for 210 min, the methylene blue (MB) degradation efficiency was 63% for g-C3N4 , 58% for TiO2 , 71% for g-C3N4-TiO2 , 85% for g-C3N4 -1% wt Fe3O4-TiO2 , 96% for g-C3N4 -5% wt Fe3O4 -TiO2 and 77% for g-C3N4-10% wt Fe3O4-TiO2 indicating that nanocomposites with 5 wt% Fe3O4 had the best photocatalytic performance. The SSA of the TiO2 , g-C3N4 , g-C3N4-TiO2 and g-C3N4-10% wt Fe3O4-TiO2 were determined using Sear's method. Finally, it is worth mentioning that the surface area of the g-C3N4-10% wt Fe3O4-TiO2 photocatalyst has been found to be 66.2 m 2 g -1

In vitro breast cancer targeting using Trastuzumab-conjugated mesoporous silica nanoparticles: Towards the new strategy for decreasing size and high drug loading capacity for drug delivery purposes in MSN synthesis

In the present study, an efficient protocol was introduced for synthesis of biocompatible mesoporous silica nanoparticles (MSN) with an adequate size and high drug loading capacity. Herein, the tri-ethanolamine, TEA, dominantly controlled the pH of solution in addition to regulate nanoparticle sizes via complexing with ortho silicate functional group. Furthermore, ammonium nitrate as a weak acid was used for micellar template extraction and the results were compared with a common salt such as sodium chloride. The obtained results of BET analysis showed ammonium nitrate led to creation of pore sizes with 3.2 nm and enhanced specific surface area with 563 m2/g which were higher than NaCl route. In the next step, the surfaces of MSNs were functionalized with particular compounds, (3- Aminopropyl) tri-ethoxysilane, APTES, applied for amine functionalization whereas 1-Ethyl-3-(3- dimethylaminopropyl)-carbodiimide/N-hydroxysuccinimide, EDC/NHS, as cross link agent was used for Trastuzumab modification of silica nanoparticles which were subsequently loaded with doxorubicin for studying the targeted breast cancer therapy. Moreover, fluorescein dye was optimized on the surface modified nanoparticles. The molecular fluorescence imaging was used to confirm the significant attachments of our surface modified MSNs to plasma membrane of breast cancer cell lines (HER2 overexpressed SKBR3 cell lines). Furthermore, drug loading capacity of the presented nano-carriers was calculated and shown to be 57.40% for doxorubicin suggesting its priority in the biological application comparing to other reported ones. Finally, quantum chemical study at B3lyp/6–311++g** level of theory was performed to reveal the pH-triggered release of doxorubicin loaded on these nanoparticles which the obtained results were in agreement with experimental evidences