BIOELECTROMAGNETICS

Characterising core body temperature response of free-moving C57BL/6 mice to 1.95 GHz whole-body radiofrequency-electromagnetic fields
Sylvester E, Deng C, McIntosh R, Iskra S, Frankland J, McKenzie R and Croft RJ
The present study investigated the core body temperature (CBT) response of free-moving adult male and female C57BL/6 mice, during and following a 2-h exposure to 1.95 GHz RF-EMF within custom-built reverberation chambers, using temperature capsules implanted within the intraperitoneal cavity and data continuously logged and transmitted via radiotelemetry postexposure. Comparing RF-EMF exposures (WBA-SAR of 1.25, 2.5, 3.75, and 5 W/kg) to the sham-exposed condition, we identified a peak in CBT within the first 16 min of RF-EMF exposure (+0.15, +0.31, +0.24, +0.37°C at 1.25, 2.5, 3.75, and 5 W/kg respectively; statistically significant at WBA-SAR ≥ 2.5 W/kg only), which largely dissipated for the remainder of the exposure period. Immediately before the end of exposure, only the CBT of the 5 W/kg condition was statistically differentiable from sham. Based on our findings, it is apparent that mice are able to effectively compensate for the increased thermal load at RF-EMF strengths up to 5 W/kg. In addition, the elevated CBT at the end of the exposure period in the 5 W/kg condition was statistically significantly reduced compared to the sham condition immediately after RF-EMF exposure ceased. This would indicate that measures of CBT following the end of an RF-EMF exposure period may not reflect the actual change in the CBT of mice caused by RF-EMF exposure in mice.
The influence of eyelashes on electric field distribution and absorbed power density in the cornea under millimeter-wave exposure
Foroughimehr N, Vilagosh Z, Yavari A and Wood A
As millimeter wave (MMW) technology, particularly in fifth-generation (5G) devices, gains prominence, there is a crucial need for comprehensive electromagnetic (EM) models of ocular tissues to understand and characterize EM exposure conditions accurately. This study employs numerical modeling to investigate the interaction between MMW and the cornea, aiming to characterize EM field distributions and absorption within an anatomically accurate eye model while considering the influence of eyelashes. Using the finite-difference time-domain (FDTD) method, we conduct simulations of EM radiation interactions from 20.0 to 100.0 GHz with a human eye model. Moreover, we analyze the temperature distribution increase within the eye model using a thermal sensor in XFdtd, employing a scheme based on the finite difference (FD) method. Our findings reveal a nonuniform distribution of the EM field, particularly intensified in corneal regions adjacent to eyelashes and eyelids. Despite similar EM field patterns, the presence or absence of eyelashes has minimal impact on temperature differences. However, the study highlights increased radiation absorption by the eyelid's epidermis at 100.0 GHz, reducing the rise in the cornea's temperature.
Numerical and analytical inspection of magnetic field effects in the radical pair mechanism by a simplified rate equation model
Deser A, Kuhne J and Leymann HAM
The radical pair mechanism is by now the most prominent candidate for a biologically relevant quantum effect of magnetic fields. Recently, N. Ikeya and J. R. Woodward demonstrated a magnetic field effect for sub-extremely low frequency (ELF) fields in the mT range by investigating the autofluorescence spectrum of flavin adenine dinucleotide in living HeLa cells. We apply a simple rate equation model to show numerically and analytically that magnetic field effects can be expected to exist in the whole ELF range.
Protective effect of radiofrequency exposure against menadione-induced oxidative DNA damage in human neuroblastoma cells: The role of exposure duration and investigation on key molecular targets
Sannino A, Allocca M, Scarfì MR, Romeo S and Zeni O
In our previous studies, we demonstrated that 20 h pre-exposure of SH-SY5Y human neuroblastoma cells to 1950 MHz, UMTS signal, at specific absorption rate of 0.3 and 1.25 W/kg, was able to reduce the oxidative DNA damage induced by a subsequent treatment with menadione in the alkaline comet assay while not inducing genotoxicity per se. In this study, the same cell model was used to test the same experimental conditions by setting different radiofrequency exposure duration and timing along the 72 h culture period. The results obtained in at least three independent experiments indicate that shorter exposure durations than 20 h, that is, 10, 3, and 1 h per day for 3 days, were still capable to exert the protective effect while not inducing DNA damage per se. In addition, to provide some hints into the mechanisms underpinning the observed phenomenon, thioredoxin-1, heat shock transcription factor 1, heat shock protein 70, and poly [ADP-ribose] polymerase 1, as key molecular players involved in the cellular stress response, were tested following 3 h of radiofrequency exposure in western blot and qRT-PCR experiments. No effect resulted from molecular analysis under the experimental conditions adopted.
Action potential threshold variability for different electrostimulation models and its potential impact on occupational exposure limit values
Soyka F, Tarnaud T, Alteköster C, Schoeters R, Plovie T, Joseph W and Tanghe E
Occupational exposure limit values (ELVs) for body internal electric fields can be derived from thresholds for action potential generation. These thresholds can be calculated with electrostimulation models. The spatially extended nonlinear node model (SENN) is often used to determine such thresholds. Important parameters of these models are the membrane channel dynamics describing the ionic transmembrane currents as well as the temperature at which the models operate. This work compares action potential thresholds for five different membrane channel dynamics used with the SENN model. Furthermore, two more detailed double-cable models by Gaines et al. (MRG-Sensory and MRG-Motor) are also considered in this work. Thresholds calculated with the SENN model and the MRG models are compared for frequencies between 1 Hz and 100 kHz and temperatures at 22°C and 37°C. Results show that MRG thresholds are lower than SENN thresholds. Deriving alternative ELVs from these thresholds shows that the alternative ELVs can change significantly with different ion channel dynamics (up to a factor of 22). Using the double cable model could lead to approximately ten times lower alternative exposure limit values. On the contrary, using the SENN model with different membrane channel dynamics could also lead to higher alternative exposure limit values. Therefore, future exposure guidelines should take the influence of different electrostimulation models into account when deriving ELVs.
The effect of mobile phone electromagnetic fields on the human resting state wake EEG and event-related potential: A systematic review and meta-analysis
Prins AC, Baas K, van der Meer JN, Jacobs M and Nederveen AJ
The rapid growth of mobile phone usage and its use of radiofrequency electromagnetic fields (RF-EMF) have raised concerns about potential health risks. Researchers have conducted studies to examine the effects of RF-EMF on the brain using electroencephalography (EEG). We conducted a systematic quality assessment and meta-analysis of published research in this field to establish high-quality studies as references for future protocols. The electronic search yielded 244 records from which a total of 51 studies were included in the review after excluding studies based on study design, and data or report availability. Of these 51 studies, 31 (61%) focused on resting state wake EEG and 20 (39%) on event-related potentials (ERP). None of the 51 studies were free from risk of bias. From the 51 included studies, we were able to use seven studies to create three different groups for meta-analysis for resting state wake EEG and five studies to create 10 different groups for meta-analysis for ERP. Per group the number of studies varies from 1 to 5. Our procedure is the first systematic quality assessment in this field and revealed three important findings. First, there is evidence of an effect on the EEG of a 2G protocol using an eyes-open condition. Second, we did not find evidence for EEG effects during task performance. This suggests that the impact of EMF during task performance is less pronounced compared to the resting state condition. Third, this meta-analysis shows that the field is unable to create an evidence base for most comparisons due to heterogeneity. We therefore advise that all future studies are double-blind in nature, adhere to the methodological standard of randomized experiments, and publish their protocols first.
Validation of mobile phone use recall in the multinational MOBI-kids study
van Wel L, Huss A, Kromhout H, Momoli F, Krewski D, Langer CE, Castaño-Vinyals G, Kundi M, Maule M, Miligi L, Sadetzki S, Albert A, Alguacil J, Aragones N, Badia F, Bruchim R, Goedhart G, de Llobet P, Kiyohara K, Kojimahara N, Lacour B, Morales-Suarez-Varela M, Radon K, Remen T, Weinmann T, Vrijheid M, Cardis E, Vermeulen R and
Potential differential and non-differential recall error in mobile phone use (MPU) in the multinational MOBI-Kids case-control study were evaluated. We compared self-reported MPU with network operator billing record data up to 3 months, 1 year, and 2 years before the interview date from 702 subjects aged between 10 and 24 years in eight countries. Spearman rank correlations, Kappa coefficients and geometric mean ratios (GMRs) were used. No material differences in MPU recall estimates between cases and controls were observed. The Spearman rank correlation coefficients between self-reported and recorded MPU in the most recent 3 months were 0.57 and 0.59 for call number and for call duration, respectively. The number of calls was on average underestimated by the participants (GMR = 0.69), while the duration of calls was overestimated (GMR = 1.59). Country, years since start of using a mobile phone, age at time of interview, and sex did not appear to influence recall accuracy for either call number or call duration. A trend in recall error was seen with level of self-reported MPU, with underestimation of use at lower levels and overestimation of use at higher levels for both number and duration of calls. Although both systematic and random errors in self-reported MPU among participants were observed, there was no evidence of differential recall error between cases and controls. Nonetheless, these sources of exposure measurement error warrant consideration in interpretation of the MOBI-Kids case-control study results on the association between children's use of mobile phones and potential brain cancer risk.
Estimates and measurements of radiofrequency exposures in smart-connected homes
Joyner K, Milligan M and Knipe P
The aim of this research was to quantify the levels of radiofrequency electromagnetic energy (RF-EME) in a residential home/apartment equipped with a range of wireless devices, often referred to as internet of things (IoT) devices or smart devices and subsequently develop a tool that could be useful for estimating the levels of RF-EME in a domestic environment. Over the course of 3 years measurements were performed in peoples' homes on a total of 43 devices across 16 device categories. Another 12 devices were measured in detail in a laboratory setup. In all a total of 55 individual devices across 23 device categories were measured. Based on this measurement data we developed predictive software that showed that even with a single device in 23 device categories operating near maximum they would, in total, produce exposures at a distance of 1 m of 0.17% of the ICNIRP (2020) public exposure limits. Measurements were also made in two separate smart apartments-one contained over 50 IoT devices and a second with over 100 IoT devices with the devices driven as hard as could reasonably be achieved. The respective 6-min average exposure level recorded were 0.0077% and 0.44% of the ICNIRP (2020) 30-min average public exposure limit.
A real-time working memory evaluation system for macaques in microwave fields
Li B, Zhang X, Qiao N, Chen J, Bi W, Zhi W, Ma L, Miao C, Wang L, Zou Y and Hu X
With the development and widespread application of electromagnetic technology, the health hazards of electromagnetic radiation have attracted much attention and concern. The effect of electromagnetic radiation on the nervous system, especially on learning, memory, and cognitive functions, is an important research topic in the field of electromagnetic biological effects. Most previous studies were conducted with rodents, which are relatively mature. As research has progressed, studies using non-human primates as experimental subjects have been carried out. Compared to rodents, non-human primates such as macaques not only have brain structures more similar to those of humans but also exhibit learning and memory processes that are similar. In this paper, we present a behavioral test system for the real-time evaluation of the working memory (WM) of macaques in a microwave environment. The system consists of two parts: hardware and software. The hardware consists of four modules: the operation terminal, the control terminal, the optical signal transmission, and detection module and the reward feedback module. The software program can implement the feeding learning task, the button-pressing learning task, and the delayed match-to-sample task. The device is useful for the real-time evaluation of the WM of macaques in microwave environments, showing good electromagnetic compatibility, a simple and reliable structure, and easy operation.
Transcriptional response of primary hippocampal neurons following exposure to 3.0 GHz radiofrequency electromagnetic fields
Cantu JC, Butterworth JW, Payne JA and Echchgadda I
Exposure to radiofrequency (RF) electromagnetic fields (EMF) has been associated with the modulation of neuronal electrophysiology and synaptic plasticity. Given the potential of these changes to coincide with alterations in gene expression, this study investigated whether a transcriptional response would occur in neurons following exposure to RF-EMF, under both thermal and nonthermal conditions. Rat primary hippocampal neurons (PHNs) underwent either a single (one-time) or a multiple (3-times, once a day) exposures to RF-EMF (3.0 GHz, CW) at two different mean specific absorption rate (SAR) values of 0.57 W/kg or 5.91 W/kg, which induced a temperature change (ΔT °C) of approximately 0.3°C or 3.6°C, respectively. Alteration in transcription in the RF-EMF-exposed PHNs versus the sham counterparts was assessed at 0, 4, and 24 h postexposure via high-throughput RNA sequencing using Illumina HiSeq. 2000. A total of 20 differentially expressed genes (DEGs) exhibited significant upregulation due to RF-EMF exposure, observed only with the high SAR dose that induced a thermal rise. However, the expression of these DEGs was not significant at 24 h postexposure. Our findings confirmed a lack of nonthermal effects on gene expression under low RF-EMF exposure conditions as evaluated. Additionally, the results indicated a slight thermal effect of exposures at the dose nearing the standards threshold of 4 W/kg; however, the effect appeared to be transient. The study suggests that RF-EMF exposures at a level close to the standards threshold, despite inducing mild temperature elevations (i.e., 3-5°C above normal), would not trigger biologically critical cellular changes.
A comparative study of simulated electric fields of transcranial magnetic stimulation targeting different cortical motor regions
Zhang JJ, Zhang BB, Bai Z and Fong KNK
This computational simulation study investigates the strength of transcranial magnetic stimulation (TMS)-induced electric fields (EF) in primary motor cortex (M1) and secondary motor areas. Our results reveal high interindividual variability in the strength of TMS-induced EF responses in secondary motor areas, relative to the stimulation threshold in M1. Notably, the activation of the supplementary motor area requires high-intensity stimulation, which could be attributed to the greater scalp-to-cortex distance observed over this area. These findings emphasize the importance of individualized planning using computational simulation for optimizing neuromodulation strategies targeting the cortical motor system.
Electromagnetic field exposure monitoring of commercial 28-GHz band 5G base stations in Tokyo, Japan
Liu S, Tobita K, Onishi T, Taki M and Watanabe S
Fifth generation (5G) wireless communication is being rolled out around the world. In this work, the latest radio frequency electromagnetic field (EMF) exposure measurement results on commercial 28-GHz band 5G base stations (BSs) deployed in the urban area of Tokyo, Japan, are presented. The measurements were conducted under realistic traffic conditions with a 5G smartphone and using both omnidirectional and horn antennas. First and foremost, in all cases, the electric-field (E-field) intensity is much lower (<-38 dB) than the exposure limits. The E-field intensities for traffic-off cases do not show any significant difference between the two antennas with the maximum being 3.6 dB. For traffic-on cases, the omnidirectional antenna can undesirably capture the radio wave from the smartphone in some cases, resulting in a 7-13 dB higher E-field intensity than that using the horn antenna. We also present comparative results between 4G long term evolution BSs and sub-6-GHz band and 28-GHz band 5G BSs and provide recommendations on acquiring meaningful EMF exposure data. This work is a further step toward the standardization of the measurement method regarding quasi-millimeter/millimeter wave 5G BSs.
Pulsed electromagnetic fields used in regenerative medicine: An in vitro study of the skin wound healing proliferative phase
Bedja-Iacona L, Scorretti R, Ducrot M, Vollaire C and Franqueville L
Numerous studies have demonstrated the efficacy of extremely low frequency-pulsed electromagnetic fields (ELF-PEMF) in accelerating the wound healing process in vitro and in vivo. Our study focuses specifically on ELF-PEMF applied with the Magnomega® device and aims to assess their effect during the main stages of the proliferative phase of dermal wound closure, in vitro. Thus, after the characterization of the EMFs delivered by the Magnomega® unit, primary culture of human dermal fibroblasts (HDFs) were exposed, or not for the control culture, to 10-12 and 100 Hz ELF-PEMF. These parameters are used in clinical practice by physiotherapists in order to enhance healing of dermal lesions in patients. HDFs proliferation was first assessed and revealed an increase in the expression of one of the two genetic markers of cell proliferation tested (PCNA and MKI67), after initial exposure of the cells to 10-12 Hz PEMF. Next, migration of HDFs was investigated by performing scratch assays on HDF layers. The observed wound closure kinetics corroborate the early organization of actin stress fibers that was revealed in the cytoplasm of HDFs exposed to 100 Hz ELF-PEMF. Also, maturation of HDFs into myofibroblasts was significantly increased in cells exposed to 10-12 or to 100 Hz PEMF. The present study is the first to demonstrate, in vitro, an early stimulation of HDFs, after their exposure to ELF-PEMF delivered by the Magnomega® device, which could contribute to an acceleration of the wound healing process.
Exposure assessment and cytogenetic biomonitoring study of workers occupationally exposed to extremely low-frequency magnetic fields
Nguyen H, Vandewalle G, Mertens B, Collard JF, Hinsenkamp M, Verschaeve L, Feipel V, Magne I, Souques M, Beauvois V and Ledent M
Human cytogenetic biomonitoring (HCB) has long been used to evaluate the potential effects of work environments on the DNA integrity of workers. However, HCB studies on the genotoxic effects of occupational exposure to extremely low-frequency electromagnetic fields (ELF-MFs) were limited by the quality of the exposure assessment. More specifically, concerns were raised regarding the method of exposure assessment, the selection of exposure metrics, and the definition of exposure group. In this study, genotoxic effects of occupational exposure to ELF-MFs were assessed on peripheral blood lymphocytes of 88 workers from the electrical sector using the comet and cytokinesis-block micronucleus assay, considering workers' actual exposure over three consecutive days. Different methods were applied to define exposure groups. Overall, the summarized ELF-MF data indicated a low exposure level in the whole study population. It also showed that relying solely on job titles might misclassify 12 workers into exposure groups. We proposed combining hierarchical agglomerative clustering on personal exposure data and job titles to define exposure groups. The final results showed that occupational MF exposure did not significantly induce more genetic damage. Other factors such as age or past smoking rather than ELF-MF exposure could affect the cytogenetic test outcomes.
New developments in cosmetic applications of electromagnetic fields: Client and occupational hazard assessment
Stam R
Energy-based devices are used to improve features of appearance for aesthetic reasons while avoiding more invasive methods. Examples of treatment targets are the reduction of wrinkles, sagging, unwanted skin lesions, body hair and excess fatty tissue, and the enhancement of muscle tissue. One treatment modality is the use of electromagnetic fields (EMF, 0‒300 GHz). The present work aims to give an up-to-date survey of cosmetic applications of EMF for professional use with an assessment of client and worker exposure and possible adverse effects. A systematic search was conducted for peer-reviewed articles (2007-2022), patents, premarket notifications, manufacturer data, and adverse effects reports. Five categories of cosmetic EMF device with increasing frequency were identified: sinusoid low frequency magnetic fields for lipolysis; pulsed low frequency magnetic fields for skin rejuvenation; pulsed low frequency magnetic fields for muscle building; radiofrequency EMF for lipolysis or skin rejuvenation; microwaves for hair removal or hyperhidrosis. In the vicinity of the last four device categories, there is a potential for exceeding the occupational exposure limits in the European Union EMF Directive, which could lead to nerve or muscle stimulation, burns or overheating. There are also potential hazards for clients or workers wearing active or passive medical devices. The severity of reported adverse effects increases with EMF frequency.
Pulsed electromagnetic fields attenuate human musculocutaneous nerve damage induced by biceps eccentric contractions
Kouzaki K and Nakazato K
Pulsed electromagnetic field (PEMF) therapy, a noninvasive treatment, has shown promise in mitigating nerve damage. However, unaccustomed exercises, such as eccentric contractions (ECCs), can damage both muscle and nerve tissue. This study investigated whether magnetic stimulation (MS) with PEMF could aid in nerve recovery after ECCs in the elbow flexors. Twenty participants were randomly assigned to either a control (CNT) or an MS group. Following ECCs, we measured the latency of the M-wave in the musculocutaneous nerve as an indicator of nerve function. Additionally, isometric torque, range of motion, and muscle pain were assessed for muscle function. Interestingly, only the CNT group exhibited a significant increase in latency on Day 2 (p < 0.05). The MS group, on the other hand, displayed an earlier recovery trend in isometric torque, range of motion, and muscle soreness. Notably, muscle soreness significantly decreased immediately after MS treatment compared to pretreatment levels. These findings suggest that MS treatment can effectively attenuate nerve damage induced by ECCs exercise.
Nonlinearities and timescales in neural models of temporal interference stimulation
Plovie T, Schoeters R, Tarnaud T, Joseph W and Tanghe E
In temporal interference (TI) stimulation, neuronal cells react to two interfering sinusoidal electric fields with a slightly different frequency ( , in the range of about 1-4 kHz, in the range of about 1-100 Hz). It has been previously observed that for the same input intensity, the neurons do not react to a purely sinusoidal signal at or . This study seeks a better understanding of the largely unknown mechanisms underlying TI neuromodulation. To this end, single-compartment models are used to simulate computationally the response of neurons to the sinusoidal and TI waveform. This study compares five different neuron models: Hodgkin-Huxley (HH), Frankenhaeuser-Huxley (FH), along with leaky, exponential, and adaptive-exponential integrate-and-fire (IF). It was found that IF models do not entirely reflect the experimental behavior while the HH and FH model did qualitatively replicate the observed neural responses. Changing the time constants and steady state values of the ion gates in the FH model alters the response to both the sinusoidal and TI signal, possibly reducing the firing threshold of the sinusoidal input below that of the TI input. The results show that in the modified (simplified) model, TI stimulation is not qualitatively impacted by nonlinearities in the current-voltage relation. In contrast, ion channels have a significant impact on the neuronal response. This paper offers insights into neuronal biophysics and computational models of TI stimulation.
Stimulus effects of extremely low-frequency electric field exposure on calcium oscillations in a human cortical spheroid
Saito A, Shiina T and Sekiba Y
High-intensity, low-frequency (1 Hz to 100 kHz) electric and magnetic fields (EF and MF) cause electrical excitation of the nervous system via an induced EF (iEF) in living tissue. However, the biological properties and thresholds of stimulus effects on synchronized activity in a three-dimensional (3D) neuronal network remain uncertain. In this study, we evaluated changes in neuronal network activity during extremely low-frequency EF (ELF-EF) exposure by measuring intracellular calcium ([Ca]) oscillations, which reflect neuronal network activity. For ELF-EF exposure experiments, we used a human cortical spheroid (hCS), a 3D-cultured neuronal network generated from human induced pluripotent stem cell (hiPSC)-derived cortical neurons. A 50 Hz sinusoidal ELF-EF exposure modulated [Ca] oscillations with dependencies on exposure intensity and duration. Based on the experimental setup and results, the iEF distribution inside the hCS was estimated using high-resolution numerical dosimetry. The numerical estimation revealed threshold values ranging between 255-510 V/m (peak) and 131-261 V/m (average). This indicates that thresholds of neuronal excitation in the hCS were equivalent to those of a thin nerve fiber.
Expression levels of tam receptors and ligands in the testes of rats exposed to short and middle-term 2100 MHz radiofrequency radiation
Katirci E, Kirimlioglu E, Oflamaz AO, Hidisoglu E, Cernomorcenco A, Yargıcoğlu P, Ozen S and Demir N
With advances in technology, the emission of radiofrequency radiation (RFR) into the environment, particularly from mobile devices, has become a growing concern. Tyro 3, Axl, and Mer (TAM) receptors and their ligands are essential for spermatogenesis and testosterone production. RFR has been shown to induce testicular cell apoptosis by causing inflammation and disrupting homeostasis. This study aimed to investigate the role of TAM receptors and ligands in the maintenance of homeostasis and elimination of apoptotic cells in the testes (weeks), short-term sham exposure (sham/1 week), and middle-term sham exposure (sham/10 weeks). Testicular morphology was assessed using hematoxylin-eosin staining, while immunohistochemical staining was performed to assess expression levels of TAM receptors and ligands in the testes of all groups. The results showed that testicular morphology was normal in the control, sham/1 week, and sham/10 weeks groups. However, abnormal processes of spermatogenesis and seminiferous tubule morphology were observed in RFR exposure groups. Cleaved Caspase 3 immunoreactivity showed statistically significant difference in 1 and 10 weeks exposure groups compared to control group. Moreover, there was no significant difference in the immunoreactivity of Tyro 3, Axl, Mer, Gas 6, and Pros 1 between groups. Moreover, Tyro 3 expression in Sertoli cells was statistically significantly increased in RFR exposure groups compared to the control. Taken together, the results suggest that RFR exposure negatively affects TAM signalling, preventing the clearance of apoptotic cells, and this process may lead to infection and inflammation. As a result, rat testicular morphology and function may be impaired.
Effects of electromagnetic pulses, exosomes inhibition and their coaction on A549 cells
Zhang Q, Hou Q and An G
Mounting literature indicates that electromagnetic pulses (EMP) is the promising modality to treat cancers with advantages such as noninvasiveness and few side-effects, but its appropriate parameters and underlying mechanisms such as its influence on tumor-derived exosomes (TDEs) are largely unknown. This study aimed to elucidate effects of EMP, exosome inhibition and their coaction on A549 lung adenocarcinoma cells. A549 cells were randomly divided into control group, GW4869 group treated by 20 μM GW4869, vehicle group treated by dimethyl sulfoxide, EMP group treated by EMP exposure, and EMPG group treated by EMP exposure combined with 20 μM GW4869. After EMP exposure, cell proliferation was determined by CCK8 assay, cell cycle and apoptosis was detected by flow cytometry, and cell migration was determined by transwell assay. The results showed that EMP or exosomes inhibition did not affect cell proliferation, cell cycle, apoptosis and cell migration (p > 0.05), but cell migration in EMPG group was significantly decreased compared with vehicle group (p < 0.05). We concluded that under the experimental condition, EMP or GW4869 alone had no effects on behaviors of A549 cells, but their coaction could effectively inhibit the migration of A549 cells.
Investigation of the effectiveness of intermittent electromagnetic field stimulation for early internal cartilaginous ossification in prechondrocytic ATDC5 cells
Iwaki T, Sawaji Y, Masaoka T, Fukada E, Date M and Yamamoto K
Pulsed electromagnetic field (PEMF) stimulation has been widely applied clinically to promote bone healing; however, its detailed mechanism of action, particularly in endochondral ossification, remains elusive, and long-term stimulation is required for its satisfactory effect. The aim of this study was to investigate the involvement of the mammalian target of rapamycin (mTOR) pathway in chondrocyte differentiation and proliferation using a mouse prechondroblast cell line (ATDC5), and establish an efficient PEMF stimulation strategy for endochondral ossification. The changes in cell differentiation (gene expression levels of aggrecan, type II collagen, and type X collagen) and proliferation (cellular uptake of bromodeoxyuridine [BrdU]) in ATDC5 cells in the presence or absence of rapamycin, an mTOR inhibitor, was measured. The effects of continuous and intermittent PEMF stimulation on changes in cell differentiation and proliferation were compared. Rapamycin significantly suppressed the induction of cell differentiation markers and the cell proliferation activity. Furthermore, only intermittent PEMF stimulation continuously activated the mTOR pathway in ATDC5 cells, significantly promoting cell proliferation. These results demonstrate the involvement of the mTOR pathway in chondrocyte differentiation and proliferation and suggest that intermittent PEMF stimulation could be effective as a stimulus for endochondral ossification during fracture healing process, thereby reducing stimulation time.