Biological effects of static magnetic fields and zinc isotopes on E. coli bacteria

I think this is the best post.  Studying the effects of a simple organism's reaction to a magnetic field, a reaction is observed, highly detailed observations are laid forth, along with supporting data.  Surely, if it affects this organism, why (or how) does it affect cancer??? For you scientists to figure out...

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The combined effects of an external SMF and the magnetic zinc isotope ⁶⁷Zn were found in the CFU number and growth rate constants of E. coli in the range 25–35 mT, and in the content of Na, Ca, and Mg in the range of 65–80 mT. The data obtained confirmed the magnetic sensitivity of intracellular enzymatic processes to SMF and magnetic moments of atomic nuclei.

The metabolism of the main elements in E. coli bacteria depend on external SMF and zinc isotopes contained in a nutrient medium. The changes in the intracellular content of P, K, Na, Ca, Mg, and Zn were observed in certain SMF ranges, for which the combined effects of external SMF and magnetic moments of atomic nuclei of zinc or magnesium on the growth and development of bacteria were found in earlier studies. The nature of these changes depends on the biological function of the chemical elements.

All observed effects of an external magnetic field and magnetic zinc isotope ⁶⁷Zn are consistent with the theory of magnetosensitivity of living organisms and confirm our previous results obtained in the earlier study of magnetic magnesium isotope. "

https://onlinelibrary.wiley.com/doi/full/10.1002/bem.22162

Princeton scientists discover a ‘tuneable’ novel quantum state of matter

The decoupling between the electrons and the arrangement of atoms was surprising enough, but then the researchers applied a magnetic field and discovered that they could turn that one line in any direction they chose. Without moving the crystal lattice, Zhang could rotate the line of electrons just by controlling the magnetic field around them.

“Sonia noticed that when you apply the magnetic field, you can reorient their culture,” Hasan said. “With human beings, you cannot change their culture so easily, but here it looks like she can control how to reorient the electrons’ many-body culture.”

The researchers can’t yet explain why.

https://www.princeton.edu/news/2018/09/12/princeton-scientists-discover-tuneable-novel-quantum-state-matter

Immune mechanisms mediating abscopal effects in radioimmunotherapy.

Radiotherapy of cancer has been traditionally considered as a local therapy without noticeable effects outside the irradiated fields. 

However, ionizing radiation exerts multiple biological effects on both malignant and stromal cells that account for a complex spectrum of mechanisms beyond simple termination of cancer cells. 

In the era of immunotherapy, interest in radiation-induced inflammation and cell death has considerably risen, since these mechanisms lead to profound changes in the systemic immune response against cancer antigens. Immunotherapies such as immunomodulatory monoclonal antibodies (anti-PD-1, anti-CTLA-4, anti-CD137, anti-OX40, anti-CD40, anti-TGFβ), TLR-agonists, and adoptive T-cell therapy have been synergistically combined with radiotherapy in mouse models. Importantly, radiation and immunotherapy combinations do not only act against the irradiated tumor but also against distant non-irradiated metastases (abscopal effects). 

A series of clinical trials are exploring the beneficial effects of radioimmunotherapy combinations. 

The concepts of crosspriming of tumor neoantigens and immunogenic cell death are key elements underlying this combination efficacy. 

Proinflamatory changes in the vasculature of the irradiated lesions and in the cellular composition of the leukocyte infiltrates in the tumor microenvironment contribute to raise or dampen cancer immunogenicity. 

It should be stressed that not all effects of radiotherapy favor antitumor immunity as there are counterbalancing mechanisms such as TGFβ, and VEGFs that inhibit the efficacy of the antitumor immune response, hence offering additional therapeutic targets to suppress. 

All in all, radiotherapy and immunotherapy are compatible and often synergistic approaches against cancer that jointly target irradiated and non-irradiated malignant lesions in the same patient.

https://www.ncbi.nlm.nih.gov/pubmed/30529041

Tumor treating fields increases membrane permeability in glioblastoma cells.

Glioblastoma is the most common yet most lethal of primary brain cancers with a one-year post-diagnosis survival rate of 65% and a five-year survival rate of barely 5%. Recently the U.S. Food and Drug Administration approved a novel fourth approach (in addition to surgery, radiation therapy, and chemotherapy) to treating glioblastoma; namely, tumor treating fields (TTFields). 

TTFields involves the delivery of alternating electric fields to the tumor but its mechanisms of action are not fully understood. Current theories involve TTFields disrupting mitosis due to interference with proper mitotic spindle assembly. 

We show that TTFields also alters cellular membrane structure thus rendering it more permeant to chemotherapeutics. Increased membrane permeability through the imposition of TTFields was shown by several approaches. 

For example, increased permeability was indicated through increased bioluminescence with TTFields exposure or with the increased binding and ingress of membrane-associating reagents such as Dextran-FITC or ethidium D or with the demonstration by scanning electron microscopy of augmented number and sizes of holes on the cellular membrane. 

Further investigations showed that increases in bioluminescence and membrane hole production with TTFields exposure disappeared by 24 h after cessation of alternating electric fields thus demonstrating that this phenomenom is reversible. 

Preliminary investigations showed that TTFields did not induce membrane holes in normal human fibroblasts thus suggesting that the phenomenom was specific to cancer cells. 

With TTFields, we present evidence showing augmented membrane accessibility by compounds such as 5-aminolevulinic acid, a reagent used intraoperatively to delineate tumor from normal tissue in glioblastoma patients. 

In addition, this mechanism helps to explain previous reports of additive and synergistic effects between TTFields and other chemotherapies. 

These findings have implications for the design of combination therapies in glioblastoma and other cancers and may significantly alter standard of care strategies for these diseases.

https://www.ncbi.nlm.nih.gov/pubmed/30534421

Ion Channel Tissue Expression Database with Small Molecule Modulators

Highlights

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Design of electroceuticals requires knowledge of ion channel targets and relevant drugs

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EDEn allows rapid determination of which ion channels are expressed in a given tissue

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EDEn also reveals what channel openers and blockers exist for any of the targets

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This platform is a key enabling step for the design of bioelectric interventions

Summary

The emerging field of bioelectricity has revealed numerous new roles for ion channels beyond the nervous system, which can be exploited for applications in regenerative medicine. Developing such biomedical interventions for birth defects, cancer, traumatic injury, and bioengineering first requires knowledge of ion channel targets expressed in tissues of interest. This information can then be used to select combinations of small molecule inhibitors and/or activators that manipulate the bioelectric state. Here, we provide an overview of electroceutical design environment (EDEn), the first bioinformatic platform that facilitates the design of such therapeutic strategies. This database includes information on ion channels and ion pumps, linked to known chemical modulators and their properties. The database also provides information about the expression levels of the ion channels in over 100 tissue types. The graphical interface allows the user to readily identify chemical entities that can alter the electrical properties of target cells and tissues.

https://www.sciencedirect.com/science/article/pii/S2589004218302323

Low‐energy low‐frequency pulsed electromagnetic fields (PEMFs) exert several protective effects

Low‐energy low‐frequency pulsed electromagnetic fields (PEMFs) exert several protective effects, such as the regulation of kinases, transcription factors as well as cell viability in both central and peripheral biological systems. 

However, it is not clear on which bases they affect neuroprotection and the mechanism responsible is yet unknown. 

In this study, we have characterized in nerve growth factor‐differentiated pheochromocytoma PC12 cells injured with hypoxia: (i) the effects of PEMF exposure on cell vitality; (ii) the protective pathways activated by PEMFs to relief neuronal cell death, including adenylyl cyclase, phospholipase C, protein kinase C epsilon and delta, p38, ERK1/2, JNK1/2 mitogen‐activated protein kinases, Akt and caspase‐3; (iii) the regulation by PEMFs of prosurvival heat‐shock proteins of 70 (HSP70), cAMP response element‐binding protein (CREB), brain‐derived neurotrophic factor (BDNF), and Bcl‐2 family proteins. 

The results obtained in this study show a protective effect of PEMFs that are able to reduce neuronal cell death induced by hypoxia by modulating p38, HSP70, CREB, BDNF, and Bcl‐2 family proteins. 

Specifically, we found a rapid activation (30 min) of p38 kinase cascade, which in turns enrolles HSP70 survival chaperone molecule, resulting in a significant CREB phosphorylation increase (24 hr). 

In this cascade, later (48 hr), BDNF and the antiapoptotic pathway regulated by the Bcl‐2 family of proteins are recruited by PEMFs to enhance neuronal survival. 

This study paves the way to elucidate the mechanisms triggered by PEMFs to act as a new neuroprotective approach to treat cerebral ischemia by reducing neuronal cell death.

https://www.researchgate.net/publication/330474940_Pulsed_electromagnetic_field_and_relief_of_hypoxia-induced_neuronal_cell_death_The_signaling_pathway_GESSI_et_al