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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 8155

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Dr. Caterina Merla

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Guest Editor

National Italian Agency for Energy, New Technologies and Sustainable Economic Development (ENEA) Division of Health Protection Technologies, 00123 Rome, Italy
Interests: bioelectromagnetics; bioelectrics; EM expsoure systems; EM interaction mechanisms; dosimetry; microdosimetry; bio-engineering; EM field medical applications

Special Issue Information

Dear Colleagues,

Electromagnetic field applications play an important role in many aspects of biomedicine, and understanding the fundamental issues of the biological and molecular processes caused by this physical interaction remains a priority. Non-thermal electromagnetic fields are used to manipulate cell and tissues in different ways, ranging from subtle modulations of peripheral nerves activities (electroceutical-based applications) to the direct stimulation of the central nervous system, as performed, for example, by TMS protocols or direct current stimulation methods. Tissue and cell manipulation are also achieved using higher electric field intensities of very short durations in the so-called electroporation-based applications. Therefore, a number of very different pathologies are currently treated, and depending on the specific applied signal sequences and targeted tissue/cells, different molecular pathways can be activated to contribute to the final treatment. The tissue/cell response is also related to mechanisms of endogenous protective systems and immune activation; therefore, understanding such further aspects in this complex interaction improves the knowledge of basic cell biology for current electromagnetic-based non-thermal therapies.

This Special Issue focuses on electromagnetic field applications in biomedical treatments and will include original articles on the molecular mechanisms of electromagnetic field applications that are useful for various therapies (e.g., cancer, neurodegenerative diseases and/or central nervous system affections, chronic inflammatory and metabolic pathologies, as well as heart arrhythmias) considering different cell types and tissues. Potential topics include, but are not limited to, molecular responses coming from intracellular targets, cell membranes, as well as stem cell compartments. New targets and emerging outcomes for novel therapies are other welcome subjects for this Special Issue.

Dr. Caterina Merla
Guest Editor

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Keywords

electroporation
transcranial magnetic stimulation
direct current stimulation
electroceutical
electromagnetic field-based therapy
bioelectromagnetic interactions

Published Papers (6 papers)

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Research

17 pages, 3762 KiB

Open AccessArticle

In Vitro Imaging and Molecular Characterization of Ca²⁺ Flux Modulation by Nanosecond Pulsed Electric Fields

by Francesca Camera, Eleonora Colantoni, Tomas Garcia-Sanchez, Barbara Benassi, Claudia Consales, Adeline Muscat, Leslie Vallet, Luis M. Mir, Franck Andre and Caterina Merla

Int. J. Mol. Sci. 2023, 24(21), 15616; https://doi.org/10.3390/ijms242115616 - 26 Oct 2023

Viewed by 1020

Abstract

In recent years, the application of pulsed electric fields with very short durations (nanoseconds) and extremely high amplitudes (MV/m) has been investigated for novel medical purposes. Various electric protocols have been explored for different objectives, including the utilization of fractionated pulse doses to enhance cell electrosensitization to the uptake of different markers or an increase in apoptosis. This study focused on the use of fluorescence imaging to examine molecular calcium fluxes induced by different fractionated protocols of short electric pulses in neuroblastoma (SH-SY5Y) and mesenchymal stem cells (HaMSCs) that were electroporated using nanosecond pulsed electric fields. In our experimental setup, we did not observe cell electrosensitization in terms of an increase in calcium flux following the administration of fractionated doses of nanosecond pulsed electric fields with respect to the non-fractionated dose. However, we observed the targeted activation of calcium-dependent genes (c-FOS, c-JUN, EGR1, NURR-1, β3-TUBULIN) based on the duration of calcium flux, independent of the instantaneous levels achieved but solely dependent on the final plateau reached. This level of control may have potential applications in various medical and biological treatments that rely on calcium and the delivery of nanosecond pulsed electric fields. Full article

(This article belongs to the Special Issue The Emerging Role of Non-ionizing Radiation in Biomedical Applications)

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19 pages, 4889 KiB

Open AccessArticle

Effects of Nanosecond Pulsed Electric Field (nsPEF) on a Multicellular Spheroid Tumor Model: Influence of Pulse Duration, Pulse Repetition Rate, Absorbed Energy, and Temperature

by Rosa Orlacchio, Jelena Kolosnjaj-Tabi, Nicolas Mattei, Philippe Lévêque, Marie Pierre Rols, Delia Arnaud-Cormos and Muriel Golzio

Int. J. Mol. Sci. 2023, 24(19), 14999; https://doi.org/10.3390/ijms241914999 - 8 Oct 2023

Viewed by 1143

Abstract

Cellular response upon nsPEF exposure depends on different parameters, such as pulse number and duration, the intensity of the electric field, pulse repetition rate (PRR), pulsing buffer composition, absorbed energy, and local temperature increase. Therefore, a deep insight into the impact of such parameters on cellular response is paramount to adaptively optimize nsPEF treatment. Herein, we examined the effects of nsPEF ≤ 10 ns on long-term cellular viability and growth as a function of pulse duration (2–10 ns), PRR (20 and 200 Hz), cumulative time duration (1–5 µs), and absorbed electrical energy density (up to 81 mJ/mm³ in sucrose-containing low-conductivity buffer and up to 700 mJ/mm³ in high-conductivity HBSS buffer). Our results show that the effectiveness of nsPEFs in ablating 3D-grown cancer cells depends on the medium to which the cells are exposed and the PRR. When a medium with low-conductivity is used, the pulses do not result in cell ablation. Conversely, when the same pulse parameters are applied in a high-conductivity HBSS buffer and high PRRs are applied, the local temperature rises and yields either cell sensitization to nsPEFs or thermal damage. Full article

(This article belongs to the Special Issue The Emerging Role of Non-ionizing Radiation in Biomedical Applications)

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17 pages, 2284 KiB

Open AccessArticle

NET Formation Was Reduced via Exposure to Extremely Low-Frequency Pulsed Electromagnetic Fields

by Caren Linnemann, Filiz Sahin, Yangmengfan Chen, Karsten Falldorf, Michael Ronniger, Tina Histing, Andreas K. Nussler and Sabrina Ehnert

Int. J. Mol. Sci. 2023, 24(19), 14629; https://doi.org/10.3390/ijms241914629 - 27 Sep 2023

Cited by 2 | Viewed by 1048

Abstract

Fracture-healing is a highly complex and timely orchestrated process. Non-healing fractures are still a major clinical problem and treatment remains difficult. A 16 Hz extremely low-frequency pulsed electromagnetic field (ELF-PEMF) was identified as non-invasive adjunct therapy supporting bone-healing by inducing reactive oxygen species (ROS) and Ca²⁺-influx. However, ROS and Ca²⁺-influx may stimulate neutrophils, the first cells arriving at the wounded site, to excessively form neutrophil extracellular traps (NETs), which negatively affects the healing process. Thus, this study aimed to evaluate the effect of this 16 Hz ELF-PEMF on NET formation. Neutrophils were isolated from healthy volunteers and exposed to different NET-stimuli and the 16 Hz ELF-PEMF. NETs were quantified using Sytox Green Assay and immunofluorescence, Ca²⁺-influx and ROS with fluorescence probes. In contrast to mesenchymal cells, ELF-PEMF exposure did not induce ROS and Ca²⁺-influx in neutrophils. ELF-PEMF exposure did not result in basal or enhanced PMA-induced NET formation but did reduce the amount of DNA released. Similarly, NET formation induced by LPS and H₂O₂ was reduced through exposure to ELF-PEMF. As ELF-PEMF exposure did not induce NET release or negatively affect neutrophils, the ELF-PEMF exposure can be started immediately after fracture treatment. Full article

(This article belongs to the Special Issue The Emerging Role of Non-ionizing Radiation in Biomedical Applications)

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14 pages, 2472 KiB

Open AccessArticle

Determination of the Impact of High-Intensity Pulsed Electromagnetic Fields on the Release of Damage-Associated Molecular Pattern Molecules

by Matej Kranjc, Tamara Polajžer, Vitalij Novickij and Damijan Miklavčič

Int. J. Mol. Sci. 2023, 24(19), 14607; https://doi.org/10.3390/ijms241914607 - 27 Sep 2023

Cited by 1 | Viewed by 1306

Abstract

High-Intensity Pulsed Electromagnetic Fields (HI-PEMF) treatment is an emerging noninvasive and contactless alternative to conventional electroporation, since the electric field inside the tissue is induced remotely by an externally applied pulsed magnetic field. Recently, HI-PEMF has been successfully used in the transfer of plasmid DNA and siRNA in vivo, with no or minimal infiltration of immune cells. In addition to gene electrotransfer, treatment with HI-PEMF has also shown potential for electrochemotherapy, where activation of the immune response contributes to the treatment outcome. The immune response can be triggered by immunogenic cell death that is characterized by the release of damage-associated molecular patterns (DAMPs) from damaged or/and dying cells. In this study, the release of the best-known DAMP molecules, i.e., adenosine triphosphate (ATP), calreticulin and high mobility group box 1 protein (HMBG1), after HI-PEMF treatment was investigated in vitro on three different cell lines of different tissue origin and compared with conventional electroporation treatment parameters. We have shown that HI-PEMF by itself does not cause the release of HMGB1 or calreticulin, whereas the release of ATP was detected immediately after HI-PEMF treatment. Our results indicate that HI-PEMF treatment causes no to minimal release of DAMP molecules, which results in minimal/limited activation of the immune response. Full article

(This article belongs to the Special Issue The Emerging Role of Non-ionizing Radiation in Biomedical Applications)

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15 pages, 9326 KiB

Open AccessArticle

Preliminary Study on the Effect of a Single High-Energy Electromagnetic Pulse on Morphology and Free Radical Generation in Human Mesenchymal Stem Cells

by Joanna Czwartos, Bernadeta Dobosz, Wiktoria Kasprzycka, Paulina Natalia Osuchowska, Małgorzata Stępińska, Elżbieta Anna Trafny, Jacek Starzyński and Zygmunt Mierczyk

Int. J. Mol. Sci. 2023, 24(8), 7246; https://doi.org/10.3390/ijms24087246 - 14 Apr 2023

Cited by 3 | Viewed by 1157

Abstract

The effect of nanosecond electromagnetic pulses on human health, and especially on forming free radicals in human cells, is the subject of continuous research and ongoing discussion. This work presents a preliminary study on the effect of a single high-energy electromagnetic pulse on morphology, viability, and free radical generation in human mesenchymal stem cells (hMSC). The cells were exposed to a single electromagnetic pulse with an electric field magnitude of ~1 MV/m and a pulse duration of ~120 ns generated from a 600 kV Marx generator. The cell viability and morphology at 2 h and 24 h after exposure were examined using confocal fluorescent microscopy and scanning electron microscopy (SEM), respectively. The number of free radicals was investigated with electron paramagnetic resonance (EPR). The microscopic observations and EPR measurements showed that the exposure to the high-energy electromagnetic pulse influenced neither the number of free radicals generated nor the morphology of hMSC in vitro compared to control samples. Full article

(This article belongs to the Special Issue The Emerging Role of Non-ionizing Radiation in Biomedical Applications)

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19 pages, 2542 KiB

Open AccessArticle

Thermomagnetic Resonance Effect of the Extremely Low Frequency Electromagnetic Field on Three-Dimensional Cancer Models

by Loredana Bergandi, Umberto Lucia, Giulia Grisolia, Iris Chiara Salaroglio, Iacopo Gesmundo, Riccarda Granata, Romano Borchiellini, Antonio Ponzetto and Francesca Silvagno

Int. J. Mol. Sci. 2022, 23(14), 7955; https://doi.org/10.3390/ijms23147955 - 19 Jul 2022

Cited by 2 | Viewed by 1676

Abstract

In our recent studies, we have developed a thermodynamic biochemical model able to select the resonant frequency of an extremely low frequency electromagnetic field (ELF-EMF) specifically affecting different types of cancer, and we have demonstrated its effects in vitro. In this work, we investigate the cellular response to the ELF electromagnetic wave in three-dimensional (3D) culture models, which mimic the features of tumors in vivo. Cell membrane was modelled as a resistor–capacitor circuit and the specific thermal resonant frequency was calculated and tested on two-dimensional (2D) and three-dimensional (3D) cell cultures of human pancreatic cancer, glioblastoma and breast cancer. Cell proliferation and the transcription of respiratory chain and adenosine triphosphate synthase subunits, as well as uncoupling proteins, were assessed. For the first time, we demonstrate that an ELF-EMF hampers growth and potentiates both the coupled and uncoupled respiration of all analyzed models. Interestingly, the metabolic shift was evident even in the 3D aggregates, making this approach particularly valuable and promising for future application in vivo, in aggressive cancer tissues characterized by resistance to treatments. Full article

(This article belongs to the Special Issue The Emerging Role of Non-ionizing Radiation in Biomedical Applications)

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