>>8753149 lb

Now you are hitting the nail on the head,

Because Vanadium, element 23

Has catalytic properties in conjunction with Iron

That is why CoVFe is the highest magnetic flux density material

And that gives it the highest possible force density

Which is useful in making the most powerful energy weapons

Including very high frequency generation like 95 GHz

As used in ADS systems which do no physical harm

But make the enemy FEEL THE PAIN

It is too involved to get into things like Q-factor here

Read this article to learn more:

https://en.wikipedia.org/wiki/Q_factor

But I'll just point out that DEW and ADS systems are of interest to the Department of Energy

Where Q level security clearance originated.

Of course Q is also used as a measure of electrical charge

And the early atom smashing beams invented by John G. Trump

Used VanDeGraaf accelerators shooting out electrically charged particles at very high speeds.

Q = Electrical charge, or Q-Factor of magnetic devices

I smell a revolution in technology in our future

Now, the catalytic effects of Vanadium with a FeFe bridge

Are also found in biological enzymes like

Vanadium nitrogenase

Which can turn Carbon Monoxide and Water into Petroleum

And it is likely that the same VFeFe CoFactor is found in rocks

Deep in the earth's crust, because the same process of petroleum creation is occurring there

And that is likely why the most common source of Vanadium

Is to mine a mineral like Asphaltite which is a very long chain hydrocarbon

That is rock-like, similar to black glass, but it has no silica

Just Hydrocarbons and Vanadium.

Note that Petroleum is also of interest to the DOE.

>>8753419

Are the other drugs with promise also zinc ionophores?

For instance Remdesavir and Artemisinin?

Looks to me like some idiot, namely you, that cannot explain themselves and thinks that spewing out obscenities makes them important.

Rod and Ring

Phi

>>8753443

We have previously reported that zinc ions exhibit anticancer activity by altering lysosome membrane permeability [15] and via gene expression regulation [16]. Zinc binding compounds, especially zinc ionophores, are a new group of potential anticancer agents that target zinc to the lysosomes and induce lysosome-mediated apoptosis of cancer cells [17]. In addition, the role of zinc in regulating autophagy has been recently realized [18]. Whereas previous studies have found that metal containing chloroquine complexes may lead to enhanced antimalarial activity [19], its interaction with zinc ions has never been investigated in any biological system. Given the reported anticancer activity of zinc ions and chloroquine and their involvement in lysosomal functions, we sought to investigate whether zinc ions interact with chloroquine and whether this interaction alters chloroquine's anticancer activity. We report that chloroquine is a zinc ionophore, which targets zinc to the lysosomes, and that the combination of zinc and chloroquine enhances their cytotoxicity and induces apoptosis in a human cancer cell model system.

>>8753443

We have discovered two metal ion binding compounds, pyrithione (PT) and hinokitiol (HK), that efficiently inhibit human rhinovirus, coxsackievirus, and mengovirus multiplication. Early stages of virus infection are unaffected by these compounds. However, the cleavage of the cellular eukaryotic translation initiation factor eIF4GI by the rhinoviral 2A protease was abolished in the presence of PT and HK. We further show that these compounds inhibit picornavirus replication by interfering with proper processing of the viral polyprotein. In addition, we provide evidence that these structurally unrelated compounds lead to a rapid import of extracellular zinc ions into cells. Imported Zn2+ was found to be localized in punctate structures, as well as in mitochondria. The observed elevated level of zinc ions was reversible when the compounds were removed. As the antiviral activity of these compounds requires the continuous presence of the zinc ionophore PT, HK, or pyrrolidine-dithiocarbamate, the requirement for zinc ions for the antiviral activity is further substantiated. Therefore, an increase in intracellular zinc levels provides the basis for a new antipicornavirus mechanism.

Curing virus infections harbors an enormous economic potential, and the search for new antiviral substances is of great interest for worldwide health. We have previously described the commonly used NF-κB inhibitor and metal ion chelator pyrrolidine-dithiocarbamate (PDTC) to significantly inhibit the replication of several picornaviruses such as human rhinovirus (HRV), poliovirus, coxsackievirus, and mengovirus (9, 22). These examples suggest that a common step in the life cycle of these picornaviruses is the target for the antiviral drug. In particular, we have demonstrated that PDTC has negative effects on picornavirus replication by influencing the processing of the viral polyprotein (21, 22).

The antiviral activity of PDTC is not restricted to the family Picornaviridae, since PDTC was shown to prevent the multiplication of human influenza virus, a member of the Orthomyxoviridae (33, 34). However, due to strong differences in the life cycle and host-cell interaction between human influenza virus and picornaviruses, it is likely that entirely different mechanisms might be relevant for the antiviral action of PDTC against these viruses.

Currently, the precise mode of the antiviral action of PDTC is unknown, although several theories have been substantiated with experimental evidence. Antioxidative properties of PDTC are postulated to be the reason for antiviral effects against influenza virus infections (33), which is not the case for human rhinovirus multiplication (9).

We have demonstrated that the antiviral effects of PDTC are metal ion dependent, and, in particular, Zn2+ ions play a pivotal role. To underline the hypothesis that influx of zinc into the cells has antiviral capacity, pyrithione (PT) and hinokitiol (HK) were examined. PT is known to be a zinc ionophore that leads to a rapid increase in intracellular zinc levels (27), and HK is a chelator of divalent metal ions (2).

We provide evidence that both PT and HK inhibit replication of picornaviruses by impairing viral polyprotein processing. The basis of the antiviral activity is dependent upon the availability of zinc ions. We show that the import of extracellular zinc ions is a key feature of the common antiviral property of these compounds.

>>8753443

Arrested autophagy may contribute to the pathogenesis of Alzheimer's disease. Because we found that chloroquine (CQ) causes arrested autophagy but clioquinol (ClioQ), a zinc ionophore, activates autophagic flux, in the present study, we examined whether ClioQ can overcome arrested autophagy induced by CQ or mutant presenilin-1 (mPS1). CQ induced vacuole formation and cell death in adult retinal pigment epithelial (ARPE-19) cells, but co-treatment with ClioQ attenuated CQ-associated toxicity in a zinc-dependent manner. Increases in lysosome dilation and blockage of autophagic flux by CQ were also markedly attenuated by ClioQ treatment. Interestingly, CQ increased lysosomal pH in amyloid precursor protein (APP)/mPS1-expressing Chinese hamster ovary 7WΔE9 (CHO-7WΔE9) cell line, and ClioQ partially re-acidified lysosomes. Furthermore, accumulation of amyloid-β (Aβ) oligomers in CHO-7WΔE9 cells was markedly attenuated by ClioQ. Moreover, intracellular accumulation of exogenously applied fluorescein isothiocyanate–conjugated Aβ1–42 was also increased by CQ but was returned to control levels by ClioQ. These results suggest that modulation of lysosomal functions by manipulating lysosomal zinc levels may be a useful strategy for clearing intracellular Aβ oligomers.

>>8753443

Several water-solubilized versions of the zinc ionophore 1-hydroxypyridine-2-thione (ZnHPT), synthesized as part of the present study, have been found both to increase the intracellular concentrations of free zinc and to produce an antiproliferative activity in exponential phase A549 human lung cancer cultures. Gene expression profiles of A549 cultures treated with one of these water-soluble zinc ionophores, PCI-5002, reveal the activation of stress response pathways under the control of metal-responsive transcription factor 1 (MTF-1), hypoxia-inducible transcription factor 1 (HIF-1), and heat shock transcription factors. Additional oxidative stress response and apoptotic pathways were activated in cultures grown in zinc-supplemented media. We also show that these water-soluble zinc ionophores can be given to mice at 100 μmol/kg (300 μmol/m2) with no observable toxicity and inhibit the growth of A549 lung and PC3 prostate cancer cells grown in xenograft models. Gene expression profiles of tumor specimens harvested from mice 4 h after treatment confirmed the in vivo activation of MTF-1–responsive genes. Overall, we propose that water-solubilized zinc ionophores represent a potential new class of anticancer agents. [Cancer Res 2008;68(13):5318–25]

>>8753443

We present data demonstrating the natural product mimic, zinaamidole A (ZNA), is a modulator of metal ion homeostasis causing cancer-selective cell death by specifically inducing cellular Zn2+-uptake in transformed cells. ZNA’s cancer selectivity was evaluated using metastatic, patient-derived breast cancer cells, established human breast cancer cell lines, and three-dimensional organoid models derived from normal and transformed mouse mammary glands. Structural analysis of ZNA demonstrated that the compound interacts with zinc through the N2-acyl-2-aminoimidazole core. Combination treatment with ZnSO4 strongly potentiated ZNA’s cancer-specific cell death mechanism, an effect that was not observed with other transition metals. We show that Zn2+-dyshomeostasis induced by ZNA is unique and markedly more selective than other known Zn2+-interacting compounds such as clioquinol. The in vivo bioactivity of ZNA was also assessed and revealed that tumor-bearing mice treated with ZNA had improved survival outcomes. Collectively, these data demonstrate that the N2-acyl-2-aminoimidazole core of ZNA represents a powerful chemotype to induce cell death in cancer cells concurrently with a disruption in zinc homeostasis.

>>8753443

Compounds that bind metals such as copper and zinc have many biological activities, including the ability to induce apoptosis in cancer cells. Although some of these compounds have been considered to act as chelators of metals, decreasing their bioavailability, others increase intracellular metal concentrations. We review recent work regarding the recognition of the biological effects of metal ionophores with different structures, particularly with regard to their actions upon cancer cells focusing on dithiocarbamates, pyrithione, and the 8‐hydroxyquinoline derivative, clioquinol. We provide a biologically based classification of metal‐binding compounds that allows an experimental distinction between chelators and ionophores that can be readily used by biologists, which may lead to further study and classification of metal‐binding drugs. Metal ionophores may kill cancer cells by a number of mechanisms, including lysosomal disruption and proteasome inhibition, and likely others. Because some of these compounds have been safely administered to animals and humans, they have the potential to become clinically useful anticancer agents. © 2009 IUBMB IUBMB Life, 61(11): 1013–1018, 2009

>>8753443

What about Vandium ionophores?

Would that be useful too?

Let's look…

>>8753707

The present study investigated the role of reactive oxygen species (ROS) in activation of nuclear factor of activated T cells (NFAT), a pivotal transcription factor responsible for regulation of cytokines, by vanadium in mouse embryo fibroblast PW cells or mouse epidermal Cl 41 cells. Exposure of cells to vanadium led to the transactivation of NFAT in a time- and dose-dependent manner. Scavenging of vanadium-induced H2O2 withN-acety-L-cyteine (a general antioxidant) or catalase (a specific H2O2 inhibitor) or the chelation of vanadate with deferoxamine, resulted in inhibition of NFAT activation. In contrast, an increase in H2O2generation by the addition of superoxide dismutase or NADPH enhanced vanadium-induced NFAT activation. This vanadate-mediated H2O2 generation was verified by both electron spin resonance and fluorescence staining assay. These results demonstrate that H2O2 plays an important role in vanadium-induced NFAT transactivation in two different cell types. Furthermore, pretreatment of cells with nifedipine, a calcium channel blocker, inhibited vanadium-induced NFAT activation, whereas A23187 and ionomycin, two calcium ionophores, had synergistic effects with vanadium for NFAT induction. Incubation of cells with cyclosporin A (CsA), a pharmacological inhibitor of the phosphatase calcineurin, blocked vanadium-induced NFAT activation. All data show that vanadium induces NFAT activation not only through a calcium-dependent and CsA-sensitive pathway but also involved H2O2 generation, suggesting that H2O2 may be involved in activation of calcium-calcineurin pathways for NFAT activation caused by vanadium exposure.

>>8753707

I don't expect anyone to understand this; I certainly don't, but I thought it was useful to illustrate how much work is ahead of you if you want to learn English.

Model compounds are described for the following biogenic vanadium systems: (i) Vanadate-ionophore interaction; (ii) vanadate-dependent haloperoxidases; (iii) vanadium-nitrogenase; (iv) vanadium-thiolate redox interaction; (v) alkyne-reductase and isonitrile-reductase/ligase activities of nitrogenases. The complexes model the coordination sphere (or part of it) of the active site in biogenic vanadium systems, and some of them are also functional mimics for biological systems and also catalyze industrially relevant reactions. Thus, penta-coordinate aminoalcohol and Schiff base complexes with NO4 donor sets mimic peroxidase activity and catalyze the peroxidation of thioethers, and isonitrile complexes model active intermediates of in vivo (by nitrogenases) and in vitro C-C coupling reactions. Dinitrogenvanadium complexes undergo reductive protonation of nitrogen to ammonia.

>>8753707

How about an 8th grade science project. One week to research metal ionophores, explain which are most useful to combat viruses, and how they accomplish that.

Think eighth graders could do that? They really should be able to because it doesn't actually require learning all the biochemistry. Just enough to make sense of the scientific papers and that should take one day.

https://en.wikipedia.org/wiki/Siderophore

>>8753707

Vanadium stimulates human bronchial epithelial cells to produce heparin-binding epidermal growth factor-like growth factor: a mitogen for lung fibroblasts.

Zhang L1, Rice AB, Adler K, Sannes P, Martin L, Gladwell W, Koo JS, Gray TE, Bonner JC.

Author information

Abstract

The bronchial epithelium is a potential source of growth factors that could mediate airway fibrosis during the progression of diseases such as asthma and chronic bronchitis. We report that conditioned medium (CM) from normal human bronchial epithelial cells (NHBECs) contains mitogenic activity for human lung fibroblasts that is blocked by the epidermal growth factor receptor (EGF-R) tyrosine kinase inhibitor AG1478 and by neutralizing antibodies raised against heparin-binding epidermal growth factor-like growth factor (HB-EGF). Neutralizing antibodies against other EGF-R ligands (EGF and transforming growth factor-alpha) or other antibodies against growth factors (platelet-derived growth factors, insulin-like growth factor-1) had no affect on the mitogenic activity of NHBEC-CM. HB-EGF messenger RNA (mRNA) expression in NHBEC was detected by reverse transcriptase/polymerase chain reaction and Northern blot analysis. HB-EGF protein was detected by enzyme-linked immunosorbent assay. Vanadium pentoxide (V2O5), a fibrogenic metal associated with occupational asthma, caused a several-fold increase in HB-EGF mRNA expression and protein, whereas the inert metal titanium dioxide had no effect on HB-EGF expression. V2O5-induced HB-EGF mRNA expression was inhibited by the EGF-R tyrosine kinase inhibitor AG1478, the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580, and the MAP kinase kinase inhibitor PD98059. Finally, HB-EGF induced the production of fibroblast growth factor (FGF)-2 by human lung fibroblasts and anti-FGF-2 antibody partially blocked the mitogenic activity of NHBEC-CM on fibroblasts. These data suggest that HB-EGF is a fibroblast mitogen produced by NHBECs and that induction of an FGF-2 autocrine loop in fibroblasts by HB-EGF accounts for part of this mitogenic activity.

>>8753707

The effects of the peroxovanadium complex potassium bisperoxo(1,10-phenanthroline)-oxovanadate (bpV[phen]) have been studied on

dopamine (DA) exocytosis in PC12 cells. Bisperoxo(1,10-phenanthroline)-oxovanadate does not elicit dopamine secretion in PC12 cells.

However, treatment of PC12 cells with 30M bpV[phen] for 20 min significantly enhances the secretion induced by the Ca2+-ionophore

A23187. The effects appear to be irreversible, and strikingly different from the transient and suppressing effects of orthovanadate, which,

like bpV[phen], is also a protein tyrosine phosphatase inhibitor. Contrastingly, the short-lived peroxovanadates, formed in situ by the addition of hydrogen peroxide and orthovanadate, are relatively ineffective. The Ca2+ chelating agent EGTA abolishes bpV[phen]-enhanced

dopamine release. The extracellular-regulated protein kinases (ERK) and synaptophysin, proteins implicated in exocytosis, are both

tyrosine-phosphorylated by bpV[phen] in a dose- and time-dependent manner, with a maximal effect at 30M. Pre-treatment of cells with

PD98059 significantly reduced dopamine release (P < 0.05). These results suggest that this peroxovanadium complex enhances dopamine

exocytosis, at least in part, by ERK-mediated signaling pathway and synaptophysin-associated phosphatase(s).

>>8753707

The potentiality of vanadium in medicinal applications.

Rehder D1.

Author information

Abstract

In the early treatment of diabetes with vanadium, inorganic vanadium compounds have been the focus of attention; organic vanadium compounds are nowadays increasingly attracting attention. A key compound is bis(maltolato)oxidovanadium, which became introduced into clinical tests Phase IIa. Organic ligands help modulate the bioavailability, transport and targeting mechanism of a vanadium compound. Commonly, however, the active onsite species is vanadyl (VO(2+)) or vanadate (H(2)VO(4) (-)), generated by biospeciation. The mode of operation can be ascribed to interaction of vanadate with phosphatases and kinases, and to modulation of the level of reactive oxygen species interfering with phosphatases and/or DNA. This operating mode has also been inferred for most cancerostatic vanadium compounds, although some, for example vanadocenes, may directly intercalate with DNA. Novel medicinal potentiality of vanadium compounds is geared towards endemic diseases in tropical countries, in particular leishmaniasis, Chagas' disease and amoebiasis, and viral infections such as Dengue fever, SARS and HIV.

>>8753707

Intensive studies have been carried out during the last two decades, on the insulinomimetic effects of vanadium. Vanadium compounds mimic most of the metabolic effects of insulin on the main tissues of the hormone in vitro. Vanadium therapy induces normoglycemia and improves glucose homeostasis in insulin deficient and insulin resistant diabetic rodents. Improved sensitivity to insulin in liver and muscle tissues of Type II diabetic patients following vanadium therapy was observed as well. The key mechanisms involved are inhibition of protein–phosphotyrosine phosphatases and activation of nonreceptor protein–tyrosine kinases, in an insulin-receptor tyrosine kinase independent fashion. Vanadate activates glucose-metabolism in vitro at a site preceding activation of phosphatidylinositol-3-kinase (PI3-kinase). Regarding inhibition of lipolysis, vanadate (but not insulin) acts at a site downstream to the activation of PI3 kinase. Additional vanadium-dependent mechanism, operating in vivo, is the restoration of glucose-6-phosphate levels in liver, muscle and adipose tissue of hyperglycemic diabetic rats. This is attributed to vanadate-dependent inhibition of liver glucose-6-phosphatase, and of nonspecific hexose-6-phosphatases of the diabetic muscle and adipose tissues. Initial clinical studies were already performed. Several beneficial effects were documented. The potential usage of vanadium in the future care of diabetes in human, however, depends on manipulations that would elevate the insulinomimetic efficacy of vanadium without increasing its toxicity. Organically chelated vanadium compounds, in particular, the l-isomer of Glu(γ) monohydroxamate (l-Glu(γ)HXM) are active in potentiating the capacity of free vanadium to activate glucose metabolism, in vitro and in diabetic rats in vivo. l-Glu(γ)HXM differs from other vanadium ligands in being an amino acid derivative that permeates into peripheral tissues through the amino acid transport system. In rat adipocytes, l-Glu(γ)HXM itself activates partially glucose metabolism, by permeating into cell interior, associating with the minute quantity of intracellular vanadium, and turning it into an insulinomimetic active species. l-Glu(γ)HXM, associates with the vanadyl (+4) cation, and the vanadate (+5) anion, at neutral pH with nearly the same binding affinity. Both these oxidation states of vanadium are insulinomimetic. The therapeutical potency of l-Glu(γ)HXM·vanadium complexes is actively studied. Preliminary results on this issue are to be presented.

>>8753890

Why do people post tiny photos of Gabrielle Epstein?