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Journal ArticleDOI: 10.1080/07391102.2020.1730972

Electric-field-induced electroporation and permeation of reactive oxygen species across a skin membrane

04 Mar 2021-Journal of Biomolecular Structure & Dynamics (J Biomol Struct Dyn)-Vol. 39, Iss: 4, pp 1343-1353
Abstract: Electroporation processes affect the permeability of cell membranes, which can be utilized for the delivery of plasma species in cancer therapy. By means of computational dynamics, many aspects of ...

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Topics: Electroporation (56%), Membrane (54%), Permeation (52%)

6 results found

Open accessJournal ArticleDOI: 10.3389/FCHEM.2020.00250
Abstract: Aquaporin-3 (AQP3) is one of the aquaglyceroporins, which is expressed in the basolateral layer of the skin membrane. Studies have reported that human skin squamous cell carcinoma overexpresses AQP3 and inhibition of its function may alleviate skin tumorigenesis. In the present study, we have applied a virtual screening method that encompasses filters for physicochemical properties and molecular docking to select potential hit compounds that bind to the Aquaporin-3 protein. Based on molecular docking results, the top 20 hit compounds were analyzed for stability in the binding pocket using unconstrained molecular dynamics simulations and further evaluated for binding free energy. Furthermore, examined the ligand-unbinding pathway of the inhibitor from its bound form to explore possible routes for inhibitor approach to the ligand-binding site. With a good docking score, stability in the binding pocket, and free energy of binding, these hit compounds can be developed as Aquaporin-3 inhibitors in the near future.

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Topics: Docking (molecular) (58%), Virtual screening (58%)

6 Citations

Open accessJournal ArticleDOI: 10.3390/MOLECULES25204601
09 Oct 2020-Molecules
Abstract: Pulsed electric field (PEF) is frequently used for intertumoral drug delivery resulting in a well-known anticancer treatment-electrochemotherapy. However, electrochemotherapy is associated with microsecond range of electrical pulses, while nanosecond range electrochemotherapy is almost non-existent. In this work, we analyzed the feasibility of nanosecond range pulse bursts for successful doxorubicin-based electrochemotherapy in vivo. The conventional microsecond (1.4 kV/cm × 100 µs × 8) procedure was compared to the nanosecond (3.5 kV/cm × 800 ns × 250) non-thermal PEF-based treatment. As a model, Sp2/0 tumors were developed. Additionally, basic current and voltage measurements were performed to detect the characteristic conductivity-dependent patterns and to serve as an indicator of successful tumor permeabilization both in the nano and microsecond pulse range. It was shown that nano-electrochemotherapy can be the logical evolution of the currently established European Standard Operating Procedures for Electrochemotherapy (ESOPE) protocols, offering better energy control and equivalent treatment efficacy.

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Topics: Electrochemotherapy (63%), Nanosecond (55%)

4 Citations

Open accessJournal ArticleDOI: 10.1080/2162402X.2021.1897295
Chaobin He1, Shuxin Sun1, Yu Zhang1, Fengxiao Xie1  +1 moreInstitutions (1)
11 Mar 2021-OncoImmunology
Abstract: Irreversible electroporation (IRE) is an effective method for treating pancreatic ductal adenocarcinoma (PDAC). It remains unclear whether IRE can induce a specific immune response by stimulating macrophages. Here, the associated markers of macrophages were analyzed after exposure to tumor culture supernatant (TSN) of tumor cells treated with electroporation. Subcutaneous and orthotopic PDAC models were also used to evaluate the effect of macrophage polarization induced by IRE. Aside from its direct killing effect, IRE could induce the immunogenic cell death of tumor cells by increasing the synthesis and secretion of damage associated molecular patterns. Moreover, IRE could increase the release of HMGB1, which activates the MAPK-p38 pathway and leads to the increased expression of M1 markers in macrophages, through binding to the receptor of the advanced glycation end-product (RAGE) receptor. M1 polarization was inhibited by the inhibitors of HMGB1 release, the RAGE receptor, and the MAPK-p38 signaling pathway, but it was activated by rHMGB1 or the stimulator of MAPK-p38. In addition, the promotion of M1 macrophage polarization was enhanced by the positive-feedback release or expression of HMGB1 and RAGE through the MAPK-ERK pathway in macrophages. The promotion of M1 macrophage polarization induced by IRE provided a specific rationale for the combination of IRE and immune therapy in treating PDAC.

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Topics: Macrophage polarization (61%), RAGE (receptor) (56%), Irreversible electroporation (54%) ... show more

2 Citations

Open accessJournal ArticleDOI: 10.33263/BRIAC123.29582969
01 Jan 2022-
Abstract: Electroporation has a specific application in the delivery of drugs into the cells. In addition, the challenge is to be able to deliver the drugs effectively. The key to the electroporation-based delivery method is regulated induced transmembrane voltage (ITMV). Recently, with the advent of COVID-19, there has been an increase in clinical trials on the delivery of DNA plasmids by electroporation. As a result, the substantial number of laboratory experiments are not feasible, thereby increasing the dependency on simulation-based research. Simulations of delivery of extracellular material into the cell depend upon molecular transport modeling in an electroporated cell. In this paper, molecular transport through a single nanopore is being studied theoretically. The closed-form expression of molecular transport is used in COMSOL Multiphysics simulation to obtain extracellular concentration variation as a function of time. Sinusoidal pulses with the varying magnitude of electric field (8kV/cm and 10 kV/cm) and time duration were used to understand pulse parameters' effect on molecular transport. The simulation results match the empirical result from the literature hence validate the simulation study. © 2021 by the authors.

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Topics: Electroporation (52%)


70 results found

Open accessJournal ArticleDOI: 10.1063/1.464397
Tom Darden1, Darrin M. York1, Lee G. Pedersen1Institutions (1)
Abstract: An N⋅log(N) method for evaluating electrostatic energies and forces of large periodic systems is presented. The method is based on interpolation of the reciprocal space Ewald sums and evaluation of the resulting convolutions using fast Fourier transforms. Timings and accuracies are presented for three large crystalline ionic systems.

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Topics: Ewald summation (69%), P3M (64%), Particle Mesh (51%)

20,639 Citations

Open accessJournal ArticleDOI: 10.1021/CT700301Q
Abstract: Molecular simulation is an extremely useful, but computationally very expensive tool for studies of chemical and biomolecular systems Here, we present a new implementation of our molecular simulation toolkit GROMACS which now both achieves extremely high performance on single processors from algorithmic optimizations and hand-coded routines and simultaneously scales very well on parallel machines The code encompasses a minimal-communication domain decomposition algorithm, full dynamic load balancing, a state-of-the-art parallel constraint solver, and efficient virtual site algorithms that allow removal of hydrogen atom degrees of freedom to enable integration time steps up to 5 fs for atomistic simulations also in parallel To improve the scaling properties of the common particle mesh Ewald electrostatics algorithms, we have in addition used a Multiple-Program, Multiple-Data approach, with separate node domains responsible for direct and reciprocal space interactions Not only does this combination of a

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Topics: Particle Mesh (50%)

12,609 Citations

Journal ArticleDOI: 10.1002/JCC.20291
David van der Spoel1, Erik Lindahl2, Berk Hess3, Gerrit Groenhof4  +2 moreInstitutions (4)
Abstract: This article describes the software suite GROMACS (Groningen MAchine for Chemical Simulation) that was developed at the University of Groningen, The Netherlands, in the early 1990s. The software, written in ANSI C, originates from a parallel hardware project, and is well suited for parallelization on processor clusters. By careful optimization of neighbor searching and of inner loop performance, GROMACS is a very fast program for molecular dynamics simulation. It does not have a force field of its own, but is compatible with GROMOS, OPLS, AMBER, and ENCAD force fields. In addition, it can handle polarizable shell models and flexible constraints. The program is versatile, as force routines can be added by the user, tabulated functions can be specified, and analyses can be easily customized. Nonequilibrium dynamics and free energy determinations are incorporated. Interfaces with popular quantum-chemical packages (MOPAC, GAMES-UK, GAUSSIAN) are provided to perform mixed MM/QM simulations. The package includes about 100 utility and analysis programs. GROMACS is in the public domain and distributed (with source code and documentation) under the GNU General Public License. It is maintained by a group of developers from the Universities of Groningen, Uppsala, and Stockholm, and the Max Planck Institute for Polymer Research in Mainz. Its Web site is

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Topics: Software suite (50%)

10,642 Citations

Open accessJournal ArticleDOI: 10.1093/BIOINFORMATICS/BTT055
Sander Pronk1, Szilárd Páll1, Szilárd Páll2, Roland Schulz3  +17 moreInstitutions (7)
01 Apr 2013-Bioinformatics
Abstract: Motivation: Molecular simulation has historically been a low-throughput technique, but faster computers and increasing amounts of genomic and structural data are changing this by enabling large-scale automated simulation of, for instance, many conformers or mutants of biomolecules with or without a range of ligands. At the same time, advances in performance and scaling now make it possible to model complex biomolecular interaction and function in a manner directly testable by experiment. These applications share a need for fast and efficient software that can be deployed on massive scale in clusters, web servers, distributed computing or cloud resources. Results: Here, we present a range of new simulation algorithms and features developed during the past 4 years, leading up to the GROMACS 4.5 software package. The software now automatically handles wide classes of biomolecules, such as proteins, nucleic acids and lipids, and comes with all commonly used force fields for these molecules built-in. GROMACS supports several implicit solvent models, as well as new free-energy algorithms, and the software now uses multithreading for efficient parallelization even on low-end systems, including windows-based workstations. Together with hand-tuned assembly kernels and state-of-the-art parallelization, this provides extremely high performance and cost efficiency for high-throughput as well as massively parallel simulations. Availability: GROMACS is an open source and free software available from Contact: Supplementary information:Supplementary data are available at Bioinformatics online.

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Topics: Software (52%), Massively parallel (51%)

5,130 Citations

Journal ArticleDOI: 10.1103/PHYSREVLETT.45.1196
Michele Parrinello1, Aneesur Rahman1Institutions (1)
Abstract: With use of a Lagrangian which allows for the variation of the shape and size of the periodically repeating molecular-dynamics cell, it is shown that different pair potentials lead to different crystal structures.

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Topics: Molecular dynamics (51%)

2,273 Citations

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