The Cellular Response Is Determined by a Combination of Different ELF-EMF Exposure Parameters: A Scope Review.

Since the establishment of regulations for exposure to extremely low-frequency (0-300) Hz electromagnetic fields, scientific opinion has prioritised the hypothesis that the most important parameter determining cellular behaviour has been intensity, ignoring the other exposure parameters (frequency, time, mode, waveform). This has been reflected in the methodologies of the in vitro articles published and the reviews in which they are included. A scope review was carried out, grouping a total of 79 articles that met the proposed inclusion criteria and studying the effects of the different experiments on viability, proliferation, apoptosis, oxidative stress and the cell cycle. These results have been divided and classified by frequency, intensity, exposure time and exposure mode (continuous/intermittent). The results obtained for each of the processes according to the exposure parameter used are shown graphically to highlight the importance of a good methodology in experimental development and the search for mechanisms of action that explain the experimental results, considering not only the criterion of intensity. The consequence of this is a more than necessary revision of current exposure protection regulations for the general population based on the reductionist criterion of intensity.

Extremely low-frequency electromagnetic field induces acetylation of heat shock proteins and enhances protein folding.

The pervasive weak electromagnetic fields (EMF) inundate the industrialized society, but the biological effects of EMF as weak as 10 µT have been scarcely analyzed. Heat shock proteins (HSPs) are molecular chaperones that mediate a sequential stress response. HSP70 and HSP90 provide cells under undesirable situations with either assisting covalent folding of proteins or degrading improperly folded proteins in an ATP-dependent manner. Here we examined the effect of extremely low-frequency (ELF)-EMF on AML12 and HEK293 cells. Although the protein expression levels of HSP70 and HSP90 were reduced after an exposure to ELF-EMF for 3 h, acetylations of HSP70 and HSP90 were increased, which was followed by an enhanced binding affinities of HSP70 and HSP90 for HSP70/HSP90-organizing protein (HOP/STIP1). After 3 h exposure to ELF-EMF, the amount of mitochondria was reduced but the ATP level and the maximal mitochondrial oxygen consumption were increased, which was followed by the reduced protein aggregates and the increased cell viability. Thus, ELF-EMF exposure for 3 h activated acetylation of HSPs to enhance protein folding, which was returned to the basal level at 12 h. The proteostatic effects of ELF-EMF will be able to be applied to treat pathological states in humans.

Extremely low frequency electromagnetic fields exposure during the prenatal and postnatal periods alters pro-inflammatory cytokines levels by gender.

Maternal exposure to the excessive electromagnetic fields is considered harmful to infants and associated with several health problems in life, such as neurological or immune diseases. In this present study we aimed to investigate the potential effects of extremely low-frequency electromagnetic field (ELF-EMF) exposure during the gestational and lactational period of dams on immune system parameters. The development of white blood cells (WBC), lymphocyte subpopulations (CD4+ T cells, CD8+ T cells, Natural Killer (NK) cells, and B cells) and production of T cell related cytokines were explored in the offsprings. Significant changes were found in WBC and lymphocyte counts. Although no changes in lymphocyte subunits were observed among groups, CD4+ cells were significantly increased in the female group exposed to ELF-EMF. Also, IL-17A and IFN-γ levels increased in plasma and spleen. The mean IL-4 level and the expression level of the IL-4 gene were not changed, in the experimental groups. But the expression of the IL-17A gene was also upregulated, which supports cytokine quantification analyses. In conclusion, ELF-EMF exposure in the prenatal and postnatal period increases the level of IL-17A in the spleen and blood of young female rats, and it upregulates IL-17 gene expression in the spleen, resulting in CD4+ cell proliferation and inflammation.

30 Hz, Could It Be Part of a Window Frequency for Cellular Response?

Many exogenous and endogenous risk factors have been proposed as precursors of brain tumors, including the exposure to non-ionizing electromagnetic fields. Nevertheless, there is still a debate among the scientific community about the hazard of the effects produced by non-ionizing radiation (NIR) because conflicting results have been found (number of articles reviewed >50). For that reason, to provide new evidence on the possible effects produced by exposure to NIR, we performed different studies with several combinations of extremely low frequencies, times, and field intensities in tumoral and non-tumoral cells. The results of our studies showed that cell viability was frequency dependent in glioblastoma cells. In fact, our results revealed that a frequency of 30 Hz-or even other frequencies close to 30 Hz-could constitute a window frequency determinant of the cellular response in tumoral and non-tumoral cells.

Wound Repair and Extremely Low Frequency-Electromagnetic Field: Insight from In Vitro Study and Potential Clinical Application.

Wound healing is a complex, staged process. It involves extensive communication between the different cellular constituents of various compartments of the skin and its extracellular matrix (ECM). Different signaling pathways are determined by a mutual influence on each other, resulting in a dynamic and complex crosstalk. It consists of various dynamic processes including a series of overlapping phases: hemostasis, inflammation response, new tissue formation, and tissue remodeling. Interruption or deregulation of one or more of these phases may lead to non-healing (chronic) wounds. The most important factor among local and systemic exogenous factors leading to a chronic wound is infection with a biofilm presence. In the last few years, an increasing number of reports have evaluated the effects of extremely low frequency (ELF) electromagnetic fields (EMFs) on tissue repair. Each experimental result comes from a single element of this complex process. An interaction between ELF-EMFs and healing has shown to effectively modulate inflammation, protease matrix rearrangement, neo-angiogenesis, senescence, stem-cell proliferation, and epithelialization. These effects are strictly related to the time of exposure, waveform, frequency, and amplitude. In this review, we focus on the effect of ELF-EMFs on different wound healing phases.

The effects of extremely low frequency electromagnetic fields exposure at 1 mT on hemogram and blood biochemisgtry in rats.

The biological effects of extremely low-frequency electromagnetic fields (ELF-EMF) exposure are not fully clarified. We conducted this investigation to explore the effects of ELF-EMF on hematologic and biochemical indexes in adult rats. Thirty adult male Sprague-Dawley rats were exposed to ELF-EMF at 1 mT for 24 weeks, while another 30 SD rats were sham exposed. During the exposure, peripheral blood was collected every 4 weeks to analyze the hematologic parameters and biochemical indexes. The morphology of liver and kidney was detected by hematoxylin-eosin staining at the end of the experiment. Exposed to ELF-EMF at 1 mT did not exert any statistic difference on hematologic parameters including total white blood cell count, neutrophil ratio, lymphocyte ratio, red blood cells, hemoglobin concentration and platelets count, compared to the control group. Similarly, biochemical indexes, such as glucose, lipid profile, liver function and renal function, were not affected by ELF-EMF exposure. In addition, no morphological change was observed in the liver and kidney from the exposure group. The exposure to ELF-EMF at the intensity of 1 mT for 24 weeks did not affect hematologic and biochemical indexes in adult rats.

Effect of extremely low frequency electromagnetic field parameters on the proliferation of human breast cancer.

Extremely low-frequency electromagnetic field (ELF-EMF) exposures influence many biological systems. These effects are mainly related to the intensity, duration, frequency, and pattern of the ELF-EMF. Our intent was to characterize the effect of specific pulsed electromagnetic fields on the in vitro proliferation of MCF-7 adenocarcinoma and MDA-MB-231 breast cancer cell lines and one non-cancerous M10 breast epithelial cell line. The following four important parameters of ELF-EMF were examined: frequencies (7.83 ± 0.3, 23.49 ± 0.3, and 39.15 ± 0.3 Hz), flux density (0.5 and 1 mT), exposure duration (12, 24, and 48 h), and the exposure methodology (continuous exposure versus switching exposure). The viability of MDA-MB-231 cells exposed to the optimized ELF-EMF pattern (7.83 ± 0.3 Hz, 1 mT, and 6 h switching exposure) was 40.1%. By contrast, the optimized ELF-EMF parameters that were most cytotoxic to breast cancer MDA-MB-231 cells were not damaging to normal M10 cells. In vitro studies also showed that exposure of MDA-MB-231 cells to the optimized ELF-EMF pattern promoted Ca2+ influx and resulted in apoptosis. These data confirm that exposure to this specific ELF-EMF pattern can influence cellular processes and inhibit cancer cell growth. The specific ELF-EMF pattern determined in this study may provide a potential anti-cancer treatment in the future.

Inhibition of B16F10 Cancer Cell Growth by Exposure to the Square Wave with 7.83+/-0.3Hz Involves L- and T-Type Calcium Channels.

Extremely low-frequency electromagnetic field (ELF-EMF) exposure influences many biological systems; these effects are mainly related to the intensity, duration, frequency, and pattern of the ELF-EMF. In this study, exposure to square wave with 7.83±0.3 Hz (sweep step 0.1 Hz) was shown to inhibit the growth of B16F10 melanoma tumor cells. In addition, the distribution of the magnetic field was calculated by Biot-Savart Law and plotted using MATLAB. In vitro studies demonstrated a decrease in B16F10 cell proliferation and an increase of Ca2+ influx after 48 h of exposure to the square wave. Ca2+ influx was also partially blocked by inhibition of voltage-gated L- and T-type Ca2+ channels. The data confirmed that the specific time-varying ELF-EMF had an anti-proliferation effect on B16F10 cells and that the inhibition is related to Ca2+ and voltage-gated L- and T-type Ca2+ channels.

Immune response of mollusk Onchidium struma to extremely low-frequency electromagnetic fields (ELF-EMF, 50 Hz) exposure based on immune-related enzyme activity and De novo transcriptome analysis.

Along with rapid offshore and onshore wind power development in modern society, extremely low frequency electromagnetic fields (ELF-EMF) is produced extensively in the habits of aquatic organisms. However, the biological effects of ELF-EMF on aquatic organisms are almost sparse. In this study, Onchidium struma without shell was chosen to aim whether ELF-EMF can elicit immune response of mollusk based on immune-related enzyme activities and gene expression through high-throughput transcriptome sequencing. Three experimental groups, i.e. ELF-EMF unexposed control group (C), ELF-EMF (50 Hz, 100 µT) exposed E1 group, and ELF-EMF (50 Hz, 500 µT) exposed E2 group, were set, and coelomocytes were collected to analyze. The results showed that total coelomocyte and spherulocyte density in E1 group increased significantly compared to groups C and E2 (P < 0.05). There were no significant differences on amoebocyte and chromatocyte density among groups C, E1 and E2. ELF-EMF exposure could significantly increase immune-related enzyme activities in coelomic fluid of O. struma, including acidic phosphatase, alkaline phosphatase, antioxidative capacity, catalase, superoxide dismutase, and polyphenol oxidase (P < 0.05). A total of 54.32 Mb and 55.27 Mb raw reads with average length of 1520 bp were obtained from coelomocytes of O. struma in unexposed and exposed groups, respectively. There were 341 differentially expressed genes (DGEs) between unexposed and exposed groups, including 209 up-regulated and 132 down-regulated unigenes. All the DGEs were allocated to 14 Kyoto Encyclopedia of Genes and Genomes pathways, and five pathways were associated with immune response, including TLR/TNF/NOD-like receptor/MAPK/Fc epsilon RI signaling pathways. Altogether, short-term (to one week) exposure of O. struma to lower luxy density ELF-EMF (<500 µT) could elicit the immune response, and antioxidant system is recommended as indicators of immunological effects. Hopefully, this study will further provide insights into exploring biomarker for evaluation of the effect of ELF-EMF exposure on aquatic organisms regarding to field density, frequency and exposure duration, and provide good guidance for exploitation and utilization of renewable energy.

Case-control study on occupational exposure to extremely low-frequency electromagnetic fields and the association with acoustic neuroma.

Exposure to extremely low-frequency electromagnetic fields (ELF-EMF) was in 2002 classified as a possible human carcinogen, Group 2B, by the International Agency for Research on Cancer at WHO based on an increased risk for childhood leukemia. In case-control studies on brain and head tumours during 1997-2003 and 2007-2009 we assessed life-time occupations in addition to exposure to different agents. The INTEROCC ELF-EMF Job-Exposure Matrix was used for associating occupations with ELF-EMF exposure (µT) with acoustic neuroma. Cumulative exposure (µT-years), average exposure (µT) and maximum exposed job (µT) were calculated. No increased risk for acoustic neuroma was found in any category. For cumulative exposure in the highest exposure category 8.52+ µT years odds ratio (OR) = 1.2, 95% confidence interval (CI) = 0.8-2.0, p linear trend = 0.37 was calculated. No statistically significant risks were found in the time windows 1-14 years, and 15+ years, respectively. In conclusion occupational ELF-EMF was not associated with an increased risk for acoustic neuroma.

Short ELF-EMF Exposure Targets SIRT1/Nrf2/HO-1 Signaling in THP-1 Cells.

Extremely low frequency electromagnetic fields (ELF-EMFs) have been known to modulate inflammatory responses by targeting signal transduction pathways and influencing cellular redox balance through the generation of oxidants and antioxidants. Here, we studied the molecular mechanism underlying the anti-oxidative effect of ELF-EMF in THP-1 cells, particularly with respect to antioxidant enzymes, such as heme oxygenase-1 (HO-1), regulated transcriptionally through nuclear factor E2-related factor 2 (Nrf2) activation. Cells treated with lipopolysaccharides (LPS) were exposed to a 50 Hz, 1 mT extremely low frequency electromagnetic fields for 1 h, 6 h and, 24 h. Our results indicate that ELF-EMF induced HO-1 mRNA and protein expression in LPS-treated THP-1 cells, with peak expression at 6 h, accompanied with a concomitant migration to the nucleus of a truncated HO-1 protein form. The immunostaining analysis further verified a nuclear enrichment of HO-1. Moreover, ELF-EMF inhibited the protein expressions of the sirtuin1 (SIRT1) and nuclear factor kappa B (NF-kB) pathways, confirming their anti-inflammatory/antioxidative role. Pretreatment with LY294002 (Akt inhibitor) and PD980559 (ERK inhibitor) inhibited LPS-induced Nrf2 nuclear translocation and HO-1 protein expression in ELF-EMF-exposed cells. Taken together, our results suggest that short ELF-EMF exposure exerts a protective role in THP-1 cells treated with an inflammatory/oxidative insult such as LPS, via the regulation of Nrf-2/HO-1 and SIRT1 /NF-kB pathways associated with intracellular glutathione (GSH) accumulation.

Effects of exposure to extremely low frequency electromagnetic fields on hippocampal long-term potentiation in hippocampal CA1 region.

Exposure to environmental electromagnetic fields, especially to the extremely low-frequency (ELF < 300 Hz) electromagnetic fields (EMFs) might produce modulation effects on neuronal activity. Long-term changes in synaptic plasticity such as long-term potentiation (LTP) involved in learning and memory may have contributions to a number of neurological diseases. However, the modulation effects of ELF-EMFs on LTP are not yet fully understood. In our present study, we aimed to evaluate the effects of exposure to ELF-EMFs on LTP in hippocampal CA1 region in rats. Hippocampal slices were exposed to magnetic fields generated by sXcELF system with different frequencies (15, 50, and 100 Hz [Hz]), intensities (0.5, 1, and 2 mT [mT]), and duration (10 s [s], 20 s, 40 s, 60 s, and 5 min), then the baseline signal recordings for 20 min and the evoked field excitatory postsynaptic potentials (fEPSPs) were recorded. We found that the LTP amplitudes decreased after magnetic field exposure, and the LTP amplitudes decreased in proportion to exposure doses and durations, suggesting ELF-EMFs may have dose and duration-dependent inhibition effects. Among multiple exposure duration and doses combinations, upon 5 min magnetic field exposure, 15 Hz/2 mT maximally inhibited LTP. Under 15 Hz/2 mT ELF-EMFs, LTP amplitude decreases in proportion to the length of exposure durations within 5 min time frame. Our findings illustrated the potential effects of ELF-EMFs on synaptic plasticity and will lead to better understanding of the influence on learning and memory.

T-Cell Differentiation to T Helper 9 Phenotype is Elevated by Extremely Low-Frequency Electromagnetic Fields Via Induction of IL-2 Signaling.

Owing to the development of information technology and the electronics industry, and the increase in the use of electronic products, an increasing number of people are exposed to electromagnetic fields (EMFs) in daily life. There has been concern about the effects of EMFs on the human body. Th9 cells, which are characterized by the generation of interleukin-(IL-9), are a recently defined subset of T helper (Th) cells. In this study, we investigated the effect of extremely low-frequency (60 Hz) EMFs, such as those generated by household power sources, at 0.8 mT intensity on CD4+ T cells. The exposure of CD4+ T cells to such EMFs under Th9-polarizing conditions increased IL-9 secretion and gene expression of transcription factors that are important for Th9 development. The expression of GATA3 increased in the early stage, and the phosphorylation of STAT5 and STAT6, which regulate the expression of GATA3, increased. In addition, EMFs increased the expression of IL-2 by the T cells. In conclusion, the differentiation of CD4+ T cells to the Th9 phenotype was increased by exposure to extremely low-frequency EMFs, and this appeared to be dependent on the IL-2 signaling pathway. Furthermore, co-cultures of EMF-exposed Th9 cells and mast cells showed an increased expression of mast cell proteases, FcεR1α, and mast cell-derived inflammatory cytokines compared with co-cultures of non-EMF-exposed Th9 cells and mast cells. Our results suggest that EMFs enhance the differentiation of CD4+ T cells to the Th9 phenotype, resulting in mast cell activation and inflammation. Bioelectromagnetics. 2019;40:588-601. © 2019 Bioelectromagnetics Society.

Lipidomic alteration and stress-defense mechanism of soil nematode Caenorhabditis elegans in response to extremely low-frequency electromagnetic field exposure.

To assess the impacts of man-made extremely low-frequency electromagnetic field (ELF-EMF) on soil ecosystems, the soil nematode was applied as a biological indicator to characterize ecotoxicity of ELF-EMF. In this paper, a soil-living model organism, Caenorhabditis elegans (C. elegans) was exposed to 50 Hz, 3 mT ELF-EMF. The integrated lipidome, proteome and transcriptome analysis were applied to elucidate physiological acclimations. Lipidomic analysis showed that ELF-EMF exposure induced significant alterations of 64 lipids, including significant elevation of triacylglycerols (TGs). Proteome results implied 157 changed protein expressions under ELF-EMF exposure. By transcriptomic analysis, 456 differently expressed genes were identified. Gene Ontology (GO) function and pathway analyses showed lipidomic alteration, mitochondrial dysfunction and the stress defense responses following ELF-EMF exposure in C. elegans. Conjoint analysis of proteome and transcriptome data showed that a higher expression of genes (sip-1, mtl-1 and rpl-11.1, etc.) were involved in stress defense responses to ELF-EMF exposure. These results indicated that ELF-EMF can induce effects on soil nematodes, mainly through disturbing lipid metabolism such as increasing TGs content, and eliciting stress defense responses. This study provided a new understanding in ELF-EMF exposure effects on soil nematodes and suggested a potential way of interpreting ELF-EMF influences on soil ecosystems.

CT2A Cell Viability Modulated by Electromagnetic Fields at Extremely Low Frequency under No Thermal Effects.

The effects produced by electromagnetic fields (EMFs) on human beings at extremely low frequencies (ELFs) have being investigated in the past years, across in vitro studies, using different cell lines. Nevertheless, the effects produced on cells are not clarified, and the cellular mechanisms and cell-signaling processes involved are still unknown. This situation has resulted in a division among the scientific community about the adequacy of the recommended level of exposure. In this sense, we consider that it is necessary to develop long-term exposure studies and check if the recommended levels of EMFs are under thermal effects. Hence, we exposed CT2A cells to different EMFs at different ELFs at short and long times. Our results showed frequency dependence in CT2A exposed during 24 h to a small EMF of 30 µT equal to those originated by the Earth and frequency dependence after the exposure during seven days to an EMF of 100 µT at different ELFs. Particularly, our results showed a remarkable cell viability decrease of CT2A cells exposed to EMFs of 30 Hz. Nevertheless, after analyzing the thermal effects in terms of HSP90 expression, we did not find thermal damages related to the differences in cell viability, so other crucial cellular mechanism should be involved.

Effects of Fifty-Hertz Electromagnetic Fields on Granulocytic Differentiation of ATRA-Treated Acute Promyelocytic Leukemia NB4 Cells.

BACKGROUND/AIMS: Life on Earth is constantly exposed to electromagnetic fields (EMFs) and the effects induced by EMFs on biological systems have been extensively studied producing different and sometimes contradictory results. Extremely low-frequency electromagnetic fields (ELF-EMFs) have shown to play a role in regulating cell proliferation and differentiation, although how EMFs influence these processes remains unclear. Human acute promyelocytic leukemia (APL) cells are characterized by the arrest of differentiation at the promyelocytic stage due to epigenetic perturbations induced by PML/RARα fusion protein (Promyelocytic Leukemia protein - PML/Retinoic Acid Receptor alpha - RARα). Therapeutic administration of all-trans retinoic acid (ATRA) re-establishes the leukemogenic mechanism re-inducing the normal differentiation processes. METHODS: We studied the effects of ELF-EMFs (50 Hz, 2 mT) on the ATRA-mediated granulocytic differentiation process of APL NB4 cells (a cell line established from the bone marrow of a patient affected by the acute promyelocytic leukemia) by monitoring cellular proliferation and morphology, nitrob lue tetrazolium (NBT) reduction and the expression of differentiation surface markers. Finally, we investigated mechanisms focusing on reactive oxygen species (ROS) generation and related molecular pathways. RESULTS: ELF-EMF exposure decreases cellular proliferation potential and helps ATRA-treated NB4 cells to mature. Furthermore, the analysis of ROS production and the consequent extracellular signal regulated kinases (ERK1/2) phosphorylation suggest that a changed intracellular oxidative balance may influence the biological effects of ELF-EMFs. CONCLUSIONS: These results indicate that the exposure to ELF-EMF promotes ATRA-induced granulocytic differentiation of APL cells.

Extremely low frequency electromagnetic field exposure and restraint stress induce changes on the brain lipid profile of Wistar rats.

BACKGROUND: Exposure to electromagnetic fields can affect human health, damaging tissues and cell homeostasis. Stress modulates neuronal responses and composition of brain lipids. The aim of this study was to evaluate the effects of chronic extremely low frequency electromagnetic field (ELF-EMF) exposure, restraint stress (RS) or both (RS + ELF-EMF) on lipid profile and lipid peroxidation in Wistar rat brain. METHODS: Twenty-four young male Wistar rats were allocated into four groups: control, RS, ELF-EMF exposure, and RS + ELF-EMF for 21 days. After treatment, rats were euthanized, the blood was obtained for quantitate plasma corticosterone concentration and their brains were dissected in cortex, cerebellum and subcortical structures for cholesterol, triacylglycerols, total free fatty acids, and thiobarbituric acid reactive substances (TBARS) analysis. In addition, fatty acid methyl esters (FAMEs) were identified by gas chromatography. RESULTS: Increased values of plasma corticosterone were found in RS and ELF-EMF exposed groups (p < 0.05), this effect was higher in RS + ELF-EMF group (p < 0.05, vs. control group). Chronic ELF-EMF exposure increased total lipids in cerebellum, and total cholesterol in cortex, but decreased polar lipids in cortex. In subcortical structures, increased concentrations of non-esterified fatty acids were observed in RS + ELF-EMF group. FAMEs analysis revealed a decrease of polyunsaturated fatty acids of cerebellum and increases of subcortical structures in the ELF-EMF exposed rats. TBARS concentration in lipids was increased in all treated groups compared to control group, particularly in cortex and cerebellum regions. CONCLUSIONS: These findings suggest that chronic exposure to ELF-EMF is similar to physiological stress, and induce changes on brain lipid profile.

Changes of cationic transport in AtCAX5 transformant yeast by electromagnetic field environments.

The electromagnetic field (EMF) is newly considered as an exogenous environmental stimulus that is closely related to ion transportation on the cellular membrane, maintaining the internal ionic homeostasis. Cation transports of Ca2+ and other metal ions, Cd2+, Zn2+, and Mn2+were studied in terms of the external Ca2+ stress, [Ca2+]ext, and exposure to the physical EMF. A specific yeast strain K667 was used for controlling CAX5 (cation/H+ exchanger) expression. Culture samples were exposed to 60 Hz, 0.1 mT sinusoidal or square magnetics waves, and intracellular cations of each sample were measured and analyzed. AtCAX5 transformant yeast grew normally under the metallic stress. However, the growth of the control group was significantly inhibited under the same cation concentration; 60 Hz and 0.1 mT magnetic field enhanced intracellular cation concentrations significantly as exposure time increased both in the AtCAX5 transformed yeast and in the control group. However, the AtCAX5-transformed yeast showed higher concentration of the intracellular cations than the control group under the same exposure EMF. AtCAX5-transformed yeasts displayed an increment in [Ca2+]int, [K+]int, [Na+]int, and [Zn2+]int concentration under the presence of both sinusoidal and square-waved EMF stresses compared to the control group, which shows that AtCAX5 expressed in the vacuole play an important role in maintaining the homeostasis of intracellular cations. These findings could be utilized in the cultivation of the crops which were resistant to excessive exogenous ions or in the production of biomass containing a large proportion of ions for nutritional food or in the bioremediation process in metal-polluted environments.

Non-Ionizing Radiation for Cardiac Human Amniotic Mesenchymal Stromal Cell Commitment: A Physical Strategy in Regenerative Medicine.

Cell therapy is an innovative strategy for tissue repair, since adult stem cells could have limited regenerative ability as in the case of myocardial damage. This leads to a local contractile dysfunction due to scar formation. For these reasons, refining strategy approaches for "in vitro" stem cell commitment, preparatory to the "in vivo" stem cell differentiation, is imperative. In this work, we isolated and characterized at molecular and cellular level, human Amniotic Mesenchymal Stromal Cells (hAMSCs) and exposed them to a physical Extremely Low Frequency Electromagnetic Field (ELF-EMF) stimulus and to a chemical Nitric Oxide treatment. Physically exposed cells showed a decrease of cell proliferation and no change in metabolic activity, cell vitality and apoptotic rate. An increase in the mRNA expression of cardiac and angiogenic differentiation markers, confirmed at the translational level, was also highlighted in exposed cells. Our data, for the first time, provide evidence that physical ELF-EMF stimulus (7 Hz, 2.5 µT), similarly to the chemical treatment, is able to trigger hAMSC cardiac commitment. More importantly, we also observed that only the physical stimulus is able to induce both types of commitments contemporarily (cardiac and angiogenic), suggesting its potential use to obtain a better regenerative response in cell-therapy protocols.

Extremely low-frequency electromagnetic field exposure enhances inflammatory response and inhibits effect of antioxidant in RAW 264.7 cells.

In recent years, there has been a dramatic increase in the number and variety of electronic devices that emit electromagnetic waves. Because people live and work in close proximity to these pieces of electrical equipment, there is growing concern surrounding the destruction of homeostasis by electromagnetic field exposure. In the present study, the effects of 60 Hz 0.8 mT extremely low-frequency electromagnetic fields (ELF-EMF) on a macrophage cell line (RAW 264.7) were examined. Under defined ELF-EMF exposure conditions, the production of nitric oxide and pro-inflammatory cytokines, TNF-α, IL-1ß, and IL-6, were increased in RAW 264.7 cells and the expression of those genes was also upregulated. However, cell proliferation was not altered. Translocation of NF-κB (nuclear factor kappa B), molecules that act downstream of the pro-inflammatory cytokines, were increased to the nucleus under ELF-EMF exposure conditions. In addition, we found that ELF-EMF exposure elevated activation of nuclear factor of activated T cells (NFAT) 2, as well as positively affected the influx of calcium. Furthermore, with both the presence of a potent antioxidant (Resveratrol) and downregulation of the antioxidant-related gene Prx-1 (Peroxiredoxin-1), ELF-EMF was associated with higher inflammatory responses of macrophages. These results suggest that an ELF-EMF amplifies inflammatory responses through enhanced macrophage activation and can decrease the effectiveness of antioxidants. Bioelectromagnetics. 38:374-385, 2017. © 2017 Wiley Periodicals, Inc.