Tuesday, October 30, 2018

National MagLab is brainstorming magnet designs

Scientists are proposing a 20-tesla instrument for human brain imaging and chemical detection — almost seven times stronger than a typical hospital MRI and twice as powerful as the strongest MRIs used in human research. Its resolution would be 10 times what can be achieved today, said Thomas Mareci, professor of biochemistry and molecular biology at the University of Florida. In a square millimeter of brain tissue, he said, that's the difference between seeing a lump representing tens of thousands of fibers and being able to identify each individual fiber.

1.2 GHz will shed more light on what goes on inside a cell, such as how they build proteins or ribonucleic acid (RNA). In the latter process, cells add about 20 new nucleotides to the molecule per second. Due to limited field strength, current instruments aren’t sensitive enough to keep up with that pace.
"If we want to get real in these kind of things, I have to actually increase my sensitivity toward the speed at which cellular machines work," said Schwalbe. "That's another dream of NMR."
Because of its very high field, the SCH can detect atoms that, until now, have been invisible to NMR, notably oxygen. The ability to observe oxygen in molecules is a game-changing capability that will allow scientists to watch the body in action at the molecular level.
"Oxygen has a number of interesting things about it," Brey said. "It's real biochemistry, not just structure — right in the active places on the molecule."
Oxygen, neurons, drug targets, weird electron behaviors: just a few of the mysteries atop scientists’ most wanted list. With the higher fields promised in next-generation magnets, researchers say, more dreamed-of discoveries will land squarely in their crosshairs.

Low-intensity electromagnetic fields induce human cryptochrome to modulate intracellular reactive oxygen species

Exposure to man-made electromagnetic fields (EMFs), which increasingly pollute our environment, have consequences for human health about which there is continuing ignorance and debate. 

Whereas there is considerable ongoing concern about their harmful effects, magnetic fields are at the same time being applied as therapeutic tools in regenerative medicine, oncology, orthopedics, and neurology. 

This paradox cannot be resolved until the cellular mechanisms underlying such effects are identified. 

Here, we show by biochemical and imaging experiments that exposure of mammalian cells to weak pulsed electromagnetic fields (PEMFs) stimulates rapid accumulation of reactive oxygen species (ROS), a potentially toxic metabolite with multiple roles in stress response and cellular ageing.

 Following exposure to PEMF, cell growth is slowed, and ROS-responsive genes are induced. 

These effects require the presence of cryptochrome, a putative magnetosensor that synthesizes ROS. 

We conclude that modulation of intracellular ROS via cryptochromes represents a general response to weak EMFs, which can account for either therapeutic or pathological effects depending on exposure. 

Clinically, our findings provide a rationale to optimize low field magnetic stimulation for novel therapeutic applications while warning against the possibility of harmful synergistic effects with environmental agents that further increase intracellular ROS.

https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2006229

Fas/FasL pathway and cytokines in keratinocytes in atopic dermatitis – Manipulation by the electromagnetic field

Apoptotic and nonapoptotic activation of the Fas/FasL-dependent signaling pathway may play a significant role in the pathogenesis of AD, by adjusting the local cytokine and chemokine environment at the site of inflammation. 

Moreover, the electromagnetic field exhibits strong immunomodulatory effects on AD-modified keratinocytes.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0205103

Static Magnetic Field Remotely Boosts the Efficiency of Doxorubicin through Modulating ROS Behaviors

Exposure to magnetic field (MF) can affect cellular metabolism remotely. 

Cardio-toxic effects of Doxorubicin (DOXO) have limited clinical uses at high dose. 

MF due to its effect on reactive oxygen species (ROS) lifetime, may provide a suitable choice to boost the efficacy of this drug at low dose. 

Here, we investigated the potential effects of homogenous static magnetic field (SMF) on DOXO-induced toxicity and proliferation rate of cancer cells. 

The results indicated that SMF similar to DOXO decreased the cell viability as well as the proliferation rate of MCF-7 and HFF cells. 

Moreover, combination of 10 mT SMF and 0.1 µM DOXO decreased the viability and proliferation rate of cancer and normal cells in a synergetic manner. 

In spite of high a GSH level in cancer cell, SMF boosts the generation and lifetime of ROS at low dose of DOXO, and overcame to GSH mediated drug resistance. 

The results also confirmed that SMF exposure decreased 50% iron content of cells, which is attributed to iron homeostasis. 

In conclusion, these findings suggest that SMF can decrease required dose of chemotherapy drugs such as DOXO and thereby decrease their side effect.

https://www.nature.com/articles/s41598-018-19247-8

Wednesday, October 24, 2018

Inhibition of Angiogenesis Mediated by Extremely Low-Frequency Magnetic Fields (ELF-MFs)

The formation of new blood vessels is an essential therapeutic target in many diseases such as cancer, ischemic diseases, and chronic inflammation. 

In this regard, extremely low-frequency (ELF) electromagnetic fields (EMFs) seem able to inhibit vessel growth when used in a specific window of amplitude. 

To investigate the mechanism of anti-angiogenic action of ELF-EMFs we tested the effect of a sinusoidal magnetic field (MF) of 2 mT intensity and frequency of 50 Hz on endothelial cell models HUVEC and MS-1 measuring cell status and proliferation, motility and tubule formation ability. MS-1 cells when injected in mice determined a rapid tumor-like growth that was significantly reduced in mice inoculated with MF-exposed cells. 

In particular, histological analysis of tumors derived from mice inoculated with MF-exposed MS-1 cells indicated a reduction of hemangioma size, of blood-filled spaces, and in hemorrhage. In parallel, in vitro proliferation of MS-1 treated with MF was significantly inhibited. 

We also found that the MF-exposure down-regulated the process of proliferation, migration and formation of tubule-like structures in HUVECs. 

Using western blotting and immunofluorescence analysis, we collected data about the possible influence of MF on the signalling pathway activated by the vascular endothelial growth factor (VEGF). In particular, MF exposure significantly reduced the expression and activation levels of VEGFR2, suggesting a direct or indirect influence of MF on VEGF receptors placed on cellular membrane. In conclusion MF reduced, in vitro and in vivo, the ability of endothelial cells to form new vessels, most probably affecting VEGF signal transduction pathway that was less responsive to activation. 

These findings could not only explain the mechanism of anti-angiogenic action exerted by MFs, but also promote the possible development of new therapeutic applications for treatment of those diseases where excessive angiogenesis is involved.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0079309

Coincident Nonlinear Changes in the Endocrine and Immune Systems due to Low-Frequency Magnetic Fields

Objective: The characteristic biological effects of low-frequency electromagnetic fields (EMFs) appear to be functional changes in the central nervous, endocrine and immune systems. 

For unapparent reasons, however, the results of similar studies have often differed markedly from one another. 

We recognized that it had generally been assumed, in the studies, that EMF effects would exhibit a dose-effect relationship, which is a basic property of linear systems. 

Prompted by recent developments in the theory on nonlinear systems, we hypothesized that there was a nonlinear relationship between EMFs and the effects they produced in the endocrine and immune systems. 

Methods: We developed a novel analytical method that could be used to distinguish between linear and nonlinear effects, and we employed it to examine the effect of EMFs on the endocrine and immune systems. Results: Mice exposed to 5 G, 60 Hz for 1–175 days in 7 independent experiments reliably exhibited changes in serum corticosterone and lymphoid phenotype when the data were analyzed while allowing that the field exposure and the resulting effects could be nonlinearly related. When the analysis was restricted to linear relationships, no effects due to the field were found. Conclusions: The results indicated that transduction of EMFs resulted in changes in both the endocrine and immune systems, and that the laws governing the changes in each system were not the type that govern conventional dose-effect relationships. Evidence based on mathematical modeling was found suggesting that the coincident changes could have been causally related.
https://www.karger.com/Article/Pdf/49009

Magnetic fields and immune response modulation

The effects of extremely low frequency magnetic fields (ELF MF) on biological systems have been studied for decades with focus on possible health risks. Many experimental studies reported various biological effects of exposure to ELF MF, however the biological relevance for these effects is unclear and a convincing evidence for mechanistic explanation is still missing. Nevertheless the modulation of oxidative response after ELF MF exposure has often been described and the release of reactive oxygen species (ROS) or other relevant effects were reported (Simkó, 2004, Simkó & Mattsson, 2004, Simkó, 2007, Mattsson & Simko, 2014). These effects are on a relatively low level (around 30-60 %). At low level “oxidative responses”, ROS can act as second messengers and activate signaling cascades, which in turn can lead to physiological responses such as gene expression, metabolic changes, cell proliferation etc., which subsequently can lead to “cell activation”. Immune-relevant cells use the reactive potential of ROS also to fulfill important physiological functions such as regulating the vascular tone and the cell functions controlled by oxygen concentration but also to activate the immune system functions. The aim of this part of the Action is to focus on possible beneficial effects related to oxidative responses and modulation of immune system functions of ELF MF in order to 1) provide a better understanding of underlying physical and biological mode of action and 2) to contribute to the development of innovative EMF-based medical treatment.
 http://cost-emf-med.eu/wp-content/uploads/2015/01/WM-prop-Myrtill-Simko-Mats-Olof-Mattsson-ELF-magnetic-fields-and-immune-response-modulation.pdf

Immune-Modulating Perspectives for Low Frequency Electromagnetic Fields in Innate Immunity

In recent years, the effects of electromagnetic fields (EMFs) on the immune system have received a considerable interest, not only to investigate possible negative health impact but also to explore the possibility to favorably modulate immune responses. 

To generate beneficial responses, the immune system should eradicate pathogens while “respecting” the organism and tolerating irrelevant antigens. 

According to the current view, damage-associated molecules released by infected or injured cells, or secreted by innate immune cells generate danger signals activating an immune response. 

These signals are also relevant to the subsequent activation of homeostatic mechanisms that control the immune response in pro- or anti-inflammatory reactions, a feature that allows modulation by therapeutic treatments. 

In the present review, we describe and discuss the effects of extremely low frequency (ELF)-EMF and pulsed EMF on cell signals and factors relevant to the activation of danger signals and innate immunity cells. 

By discussing the EMF modulating effects on cell functions, we envisage the use of EMF as a therapeutic agent to regulate immune responses associated with wound healing.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5879099/

Monday, October 22, 2018

Specifically Targeted Electromagnetic Fields Arrest Proliferation of Glioblastoma Multiforme U-87 Cells in Culture.

Abstract

BACKGROUND/AIM:

Glioblastoma multiforme is an aggressive primary tumor that arises in the glial cells of the brain. Standardized first-line treatment has considerable morbidity and less than one-year median survival after intervention. Ultra-low intensity electromagnetic fields have been shown to interact with biological organisms without anticipated deleterious side-effects. The aim of the study was to determine if a novel, non-invasive application of non-ionizing radiation has an inhibitory effect on proliferation of glioblastoma multiforme cells.

MATERIALS AND METHODS:

U-87 MG cells were continuously exposed for 54 h to an electromagnetic field tuned to simultaneously interact with DNA/RNA oligonucleotides (mutated alpha-kinase 2 gene/Hsa-miR-381-5p respectively) and proteins (HSP70/CHI3L1).

RESULTS:

Exposed cells demonstrated a significant inhibition of cell growth and concurrent increase in cell death.

CONCLUSION:

This technology induces cell death by novel non-cytotoxic mechanisms unlikely to induce side-effects in patients; can be customized for individual tumors and may contribute to the emerging strategy of personalized medicine.

https://www.ncbi.nlm.nih.gov/pubmed/29848672

Monday, October 15, 2018

Electromagnetic field investigation on different cancer cell lines

There is a strong interest in the investigation of extremely low frequency Electromagnetic Fields (EMF) in the clinic. While evidence about anticancer effects exists, the mechanism explaining this effect is still unknown.

Methods

We investigated in vitro, and with computer simulation, the influence of a 50 Hz EMF on three cancer cell lines: breast cancer MDA-MB-231, and colon cancer SW-480 and HCT-116. After 24 h preincubation, cells were exposed to 50 Hz extremely low frequency (ELF) radiofrequency EMF using in vitro exposure systems for 24 and 72 h. A computer reaction-diffusion model with the net rate of cell proliferation and effect of EMF in time was developed. The fitting procedure for estimation of the computer model parameters was implemented.

Results

Experimental results clearly showed disintegration of cells treated with a 50 Hz EMF, compared to untreated control cells. A large percentage of treated cells resulted in increased early apoptosis after 24 h and 72 h, compared to the controls. Computer model have shown good comparison with experimental data.

Conclusion

Using EMF at specific frequencies may represent a new approach in controlling the growth of cancer cells, while computer modelling could be used to predict such effects and make optimisation for complex experimental design. Further studies are required before testing this approach in humans.
https://cancerci.biomedcentral.com/articles/10.1186/s12935-014-0084-x

Potential Energy and the Body Electric

From MIT:
Physics tells us that potential energy is the capacity to do work that a body possesses as a result of its position in electric, magnetic, or gravitational fields. Thinking of “potentiality” in an electric idiom and with reference to its place in human biological processes that implicate electric phenomena, such as the pulses of action potentials that animate the heart and brain, can afford novel angles into contemporary biomedical enactments of humanness. This paper explores the material and rhetorical power of electric potential in cardiac and neurological medicine, paying attention to how discourses of “waves” of energy format the way scientists apprehend bodies as emplaced in time—in a time that can be about both cyclicity and futurity. Attention to electrophysiological phenomena may enrich the way anthropologists of the biosciences think about potentiality, taking scholars beyond our established attentions to the genetic, cellular, or pharmacological to think about the body electric.
https://www.journals.uchicago.edu/doi/full/10.1086/670968

Thursday, October 11, 2018

Cancer Stem Cells: Foe or Reprogrammable Cells for Efficient Cancer Therapy?

"The ultimate goal should not be to destroy cancer stem cells, but to differentiate and reprogram them"

Extremely – low frequency pulsed electromagnetic fields (ELF-MF) of 50 HZ, 0.8mTesla (rms), are able to orchestrate stem cell commitment towards one of the most complex embryogenetic outcomes, inducing cardiogenesis in embryonic stem cells [72]. ELF-MF are also able to modulate a cardiogenic program throughout the adulthood, as shown by the ability to increase the expression of genes needed for cardiogenesis and the maintenance of a myocardial phenotype in adult ventricular cardiomyocytes [73].
We have recently shown that asymmetrically conveyed electromagnetic fields (ACEF) of 2.4 GHz optimize the expression of pluripotency in mouse ES cells, inducing myocardial, neuronal and skeletal muscle differentiation [74]. Similar results are obtained upon exposure to ACEF of ADhMSCs [75]. This effect is the result of a fine modulation (initial increase and subsequent transcriptional inhibition) of the expression of stemness related genes [75]. Exposure to ACEF was able to induce a biphasic effect, i.e. overexpression followed by transcriptional inhibition of Sox2, Nanog, Oct3/4, Klf4 and c-myc in human skin fibroblasts, affording for the first time a direct high-yield reprogramming of adult nonstem somatic cells into myocardial, neural and skeletal muscle cells (about 15-20% for each phenotypic commitment) [76].
For the first time, through the exposure to ACEF we were able to reverse the process of stem cell senescence in human adult stem cells (ADhMSCs) subjected to prolonged (30 to 90 days) in vitro expansion [77, 78]. This effect resulted from and was associated with (i) the activation of a telomerase dependent pathway, linked to the re-expression of TERT, the gene coding for the catalytic core of telomerase with subsequent increase in telomere length [77], (ii) the induction of a telomerase independent pathway associated with the activation of Bmi-1 and the transient increase in the expression of pluripotency genes, such as Nanog, Sox2 and Oct4 [77], and (iii) the resumption of multilineage differentiation potential, as shown by recovery of high throughput of differentiation along vasculogenic, osteogenic, and adipogenic fates [78].
On the whole, these findings suggest that electromagnetic fields may have a role not only in the specification but also in the persistence of a complex cellular identity. The ability of electromagnetic fields to drive efficient cardiogenesis in both embryonic and adult stem cells and to reprogram even human skin fibroblasts into myocardial-like cells poses intriguing trans-disciplinary musing. In fact, the heart has the lowest risk for primary malignant transformation, which may very rarely develop in the form of cardiac sarcomas [79-81]. Cardiogenesis is the first morphogenetic event in different animal species, including humans. The risk for tumorigenesis throughout embryo development is also very rare [5-7]. The canonical view speculating that primary cardiac malignant tumors are so rare since cardiac cells divide very rarely appears to be too simplistic. An alternative although nonmutually exclusive hypothesis may consider the heart as a tumor suppressor organ, capable of secreting a large network of growth regulatory and differentiating peptides that may potentially limit the onset and progression of a local cancer. In this regard, the attainment of cardiogenesis in the presence of either chemical agents or physical stimulation encompasses the transcription and protein expression of endorphin peptides [33]. These molecules, besides their role in cardiogenesis [55-57], have long been shown to act as negative regulators for the development and spreading of different types of cancer [82-87].
In isolated (stem) cell nuclei endorphin peptides have been shown to bind and activate nuclear receptors and signaling leading to the transcription of their own coding gene (self-sustaining loop), as well as the transcription of the cardiogenic genes GATA4 and Nkx-2.5 [88, 56]. These findings suggest that a consistent part of the action of these growth factors on stem cell dynamics may have occurred intracellularly (intracrine action) [89, 90]. Cell plasma membrane has long been considered an insuperable barrier for hydrosoluble peptides. The discovery that regulatory peptides and transcription factors can be exchanged among cells being packaged inside exosomes, acting in an intracrine fashion, discloses novel paradigms in cell-to-cell communication and adds further relevance for intracrine regulation of cell biology [90, 91]. We cannot exclude that cardiogenesis, within its morphogenetic role, may act as a paracrine/intracrine process that contributes to make the developing embryo remarkably refractory to cancerogenic risks. Whether exposure of human cancer stem cells to electromagnetic fields may resume the ability to differentiate along a cardiogenic lineage and other differentiation patterns remain to be elucidated. Addressing this issue will require thorough investigation in vitro and in vivo in different animal models for cancerogenesis.
http://jnanoworld.com/articles/v1n3/nwj-010-carlo-ventura.html