Altered TRPM7-Dependent Calcium Influx in Natural Killer Cells of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

[SWAlexander]

TRPM7 regulates phagocytosis and clearance of Candida albicans

Thanks. That´s it.
I have candida but don't know which one. I cannot have it tested in Germany.
Candida albicans is the most commonly isolated species from clinical infections.

I´m taking Zinc for a month now and show a slight skin improvement.

 

[Wishful]

What could the amplifier be?

Neurons are amplifiers. Depending on the situation, a single transmitter molecule can trigger the release of a huge number of transmitter molecules to the next neuron. Glia might also have amplification functions. There are probably molecular processes in and around cells that qualify as amplifiers (one molecule of x triggers RNA production of z molecules of y). Microbes could act as amplifiers too: releasing hormone x could cause species y to multiply, releasing chemical z, which in turn increases hormone x.

Feedback loops aren't limited to single amplifiers. You can have any number of individual amplifiers in a loop. In the human body, chemokine A could cause vasoconstriction which causes the liver to produce less B, which causes the thyroid gland to produce more C, ... which causes gut microbe Z to release something which causes the intestinal immune cells to release more cytokine A. Amplifiers and feedback loops are everywhere.

Would you describe it as an energy boost?

No, especially if you are defining "energy" as "feeling more energetic" or "able to walk further". A power amplifier does "boost power" in that 1 mW of input power results in maybe 10 kW of output power, but the power source loses that 10 kW of power, so what is boosted is a matter of definition.

If you think of a basic electronic amplifier with a feedback loop, the gain is positive or negative. Typically it's negative, because the amplifier's gain without feedback might be 1,000,000 or more. Negative feedback is added to drop that to what is desired, such as making your earphone power levels 5x greater than the music device's "audio output". If the feedback goes positive, the output of the amplifier snaps to the maximum voltage (positive or negative) and stays there, locked in that state because positive feedback keeps reinforcing that voltage.

In terms of ME, there could be some feedback loop, involving just a few cells or maybe hundreds of "amplifiers" throughout the body, and some people are susceptible to having that loop go from slightly negative to slightly positive, and it only takes "slightly positive" to lock up. Evolution probably eliminated lots of variations that led to positive loops in the body. ME either isn't strong enough at reducing reproduction rates, or maybe there's a recent environmental factor that plays a role.

 

[SWAlexander]

Wow. What a good comparison. I never thought this way.
Are you saying we, our body function with less energy and regenerate only half of what we really would need?
Could it mean that our neurons limping (slowing down) while delivering messages? But why? Is it a demyelinating disease, (myelin sheath)? Or Cell nucleus malfunction?
Oh dear. I must let it set in my brain for a while. I must find my brain department for practical thinking. Thanks.

I just found this and must bring this in to the conversation:
"Brain cells that are covered with myelin propagate signals faster."

https://twitter.com/i/web/status/1716416426599395437

 

[SWAlexander]

One other thought on candida.

A friend took Nystatin. She wrote:
"I had heavy pain all over my body and it disappeared. l made a mistake and thought ME was caused by Candida. As it turned out it was a very good mistake. Yeast overgrowth affects the brain."

Yes, Nystatin is an antifungal medication commonly used to treat fungal infections, including those caused by Candida species. It works by binding to sterols in the fungal cell membrane, which alters the permeability of the membrane and leads to cell death. Nystatin is often prescribed for oral thrush (a Candida infection of the mouth) and other topical fungal infections.

However.
The concept of Candida directly causing overgrowth in the brain is controversial and not widely accepted within mainstream medicine. Why:

1. Candida Infections in the Brain: In very rare cases, Candida can cause a brain abscess or meningitis, particularly in immunocompromised individuals (e.g., patients with HIV/AIDS, transplant recipients on immunosuppressive therapy, or patients with cancer). However, these are severe, acute conditions that are very different from the chronic symptoms often associated with "systemic Candida" or "yeast overgrowth" claims.
2. "Brain Fog" and Candida: Some alternative medicine practitioners and their patients report "brain fog" (a term that can encompass various symptoms like confusion, lack of focus, and poor memory) as a symptom of systemic Candida overgrowth, which is often referred to as Candida overgrowth syndrome or chronic Candidiasis. However, this diagnosis is controversial, and there's limited scientific evidence to support the idea that Candida overgrowth can cause these kinds of neuropsychiatric symptoms in otherwise healthy people.
3. Gut-Brain Axis: There's growing interest in the gut-brain axis, which is the bidirectional communication between the gut and the brain. Some researchers hypothesize that changes in the gut microbiota could influence brain function and behavior. While this is a promising area of research, it's still in the early stages, and the specifics of how Candida might play a role (if any) are not well-understood.
4. Candida Die-off and Toxins: Some proponents of the Candida overgrowth hypothesis suggest that when Candida cells die, they release toxins that can affect the brain. However, this idea isn't widely supported by scientific evidence.

 

[Violeta]

One other thought on candida.

A friend took Nystatin. She wrote:
"I had heavy pain all over my body and it disappeared. l made a mistake and thought ME was caused by Candida. As it turned out it was a very good mistake. Yeast overgrowth affects the brain."

Yes, Nystatin is an antifungal medication commonly used to treat fungal infections, including those caused by Candida species. It works by binding to sterols in the fungal cell membrane, which alters the permeability of the membrane and leads to cell death. Nystatin is often prescribed for oral thrush (a Candida infection of the mouth) and other topical fungal infections.

However.
The concept of Candida directly causing overgrowth in the brain is controversial and not widely accepted within mainstream medicine. Why:

1. Candida Infections in the Brain: In very rare cases, Candida can cause a brain abscess or meningitis, particularly in immunocompromised individuals (e.g., patients with HIV/AIDS, transplant recipients on immunosuppressive therapy, or patients with cancer). However, these are severe, acute conditions that are very different from the chronic symptoms often associated with "systemic Candida" or "yeast overgrowth" claims.
2. "Brain Fog" and Candida: Some alternative medicine practitioners and their patients report "brain fog" (a term that can encompass various symptoms like confusion, lack of focus, and poor memory) as a symptom of systemic Candida overgrowth, which is often referred to as Candida overgrowth syndrome or chronic Candidiasis. However, this diagnosis is controversial, and there's limited scientific evidence to support the idea that Candida overgrowth can cause these kinds of neuropsychiatric symptoms in otherwise healthy people.
3. Gut-Brain Axis: There's growing interest in the gut-brain axis, which is the bidirectional communication between the gut and the brain. Some researchers hypothesize that changes in the gut microbiota could influence brain function and behavior. While this is a promising area of research, it's still in the early stages, and the specifics of how Candida might play a role (if any) are not well-understood.
4. Candida Die-off and Toxins: Some proponents of the Candida overgrowth hypothesis suggest that when Candida cells die, they release toxins that can affect the brain. However, this idea isn't widely supported by scientific evidence.

Candida Infections and Therapeutic Strategies: Mechanisms of Action for Traditional and Alternative Agents​

Giselle C. de Oliveira Santos1† Cleydlenne C. Vasconcelos1† Alberto J. O. Lopes2 Maria do S. de Sousa Cartágenes2

Allan K. D. B. Filho3 Flávia R. F. do Nascimento4 Ricardo M. Ramos5 Emygdia R. R. B. Pires6 Marcelo S. de Andrade2 Flaviane M. G. Rocha7 Cristina de Andrade Monteiro7,8*

https://www.frontiersin.org/articles/10.3389/fmicb.2018.01351/full

Candida species, opportunistic pathogens, are a major cause of morbidity and mortality worldwide and thus represents a serious threat to public health (Pfaller et al., 2014; Matthaiou et al., 2015; Pappas et al., 2016). Further, Candida species can cause vaginitis, oral candidiasis, cutaneous candidiasis, candidemia, and systemic infections (Wächtler et al., 2012). Candidemia is the most frequent hospital infection accounting for up to 15% of bloodstream infections, and Candida species are the main causative agents in 50–70% of systemic fungal infections (Cornely et al., 2012; Lionakis and Netea, 2013; Barchiesi et al., 2016).

Candida albicans is the pathogenic species most frequently isolated. However, other species such as C. glabrata, C. tropicalis, C. parapsilosis, C. krusei, C. famata, C. guilliermondii, and C. lusitaniae have been increasingly isolated, mainly in human immunodeficiency virus (HIV)-infected individuals (Brunke and Hube, 2013; Ferreira et al., 2013; Mayer et al., 2013; Patil et al., 2015; Barchiesi et al., 2016).

The pathogenesis of Candida species is poorly understood, and the rate of infections is increasing rapidly. Further, a steady increment in resistance to traditional antifungal has resulted in the need to control Candida infections through early diagnosis and prevention of candidiasis.

 

[SWAlexander]

Candida species is poorly understood

Great. I read it and I think I forgot to post it.
This is what worries me most: "Candida species is poorly understood" How many were never diagnosed?
I think Dr. McMillan has a video lecture on Candid and COVID:

 

[Wishful]

Is it a demyelinating disease,

I think the evidence is that it isn't. Surely autopsies or brain scans would have revealed significant demyelination. I think there's a more subtle abnormality involved, such as astrocyte processes working slightly abnormally, or some other mechanism that is too small or fast-acting to be measured by present technology. A couple of months ago was an announcement of a new microscopy technique that could actually image some really tiny (but possibly important) features on glial processes. Are these tiny features abnormal in PWME? I'm sure no one has looked yet. Are glial peroxysomes carrying only 1/3rd of some specific catalyst? Do we have the technology to check that yet? I'm still kind of expecting that any day now, some research will discover that "what everyone knows" about the brain is completely wrong, and maybe neurons are using quantum teleportation to move around, or trading dark matter molecules.

 

[SWAlexander]

Surely autopsies or brain scans would have revealed significant demyelination.

Allow me to disagree with this.
Since demyelination is in part related to the reduction of white brain matter (which I have been diagnosed with) I started looking into it a few years ago. Even more so now after COVID and having brain fog after vaccination, I decided to publish a small part of my collected findings on my blog.

Neuron Demyelinating related to many Illneses​

About glial cells occupying the lateral ventricle wall of the brain is my next reading.

 

[Violeta]

Isn't strange that agonism reduces influx and antagonism increases influx? I'm having difficulty understanding this.

I actually read in one study that agonism induces inhibition, and it's not specific to people with ME/CFS.

 

[ruben]

Thanks. That´s it.
I have candida but don't know which one. I cannot have it tested in Germany.
Candida albicans is the most commonly isolated species from clinical infections.

I´m taking Zinc for a month now and show a slight skin improvement.

Ah, candida. A specialist private doctor I was seeing back in the 1980s put me on "nystatin" for this back then! Another example I suppose of how completely "in the dark" we still are on everything concerning ME/CFS

 

[Violeta]

I actually read in one study that agonism induces inhibition, and it's not specific to people with ME/CFS.

This makes sense when you realize TRPM3 channels are also found in neurons and in fact inhibiting the channel would help reduce neuropathic pain.



"TRPM3 is expressed in peripheral sensory neurons of the dorsal root ganglia, and they are activated by high temperatures.[8] Genetic deletion of TRPM3 in mice reduces sensitivity to noxious heat, as well as inflammatory thermal hyperalgesia.[8][9] Inhibitors of TRPM3 were also shown to reduce noxious heat and inflammatory heat hyperalgesia,[10][11][9] as well as reduce heat hyperalgesia and spontaneous pain in nerve injury induced neuropathic pain.[9]"

 

[Violeta]

This makes sense when you realize TRPM3 channels are also found in neurons and in fact inhibiting the channel would help reduce neuropathic pain.



"TRPM3 is expressed in peripheral sensory neurons of the dorsal root ganglia, and they are activated by high temperatures.[8] Genetic deletion of TRPM3 in mice reduces sensitivity to noxious heat, as well as inflammatory thermal hyperalgesia.[8][9] Inhibitors of TRPM3 were also shown to reduce noxious heat and inflammatory heat hyperalgesia,[10][11][9] as well as reduce heat hyperalgesia and spontaneous pain in nerve injury induced neuropathic pain.[9]"

So the original study was about TRPM7, and actually how it is related to TRPM3. So the study ends saying that, "Several studies have demonstrated TRPM3 dysfunction in the NK cells of ME/CFS patients, which may alter the activity of other molecules, including TRPM7. The present study identified that Ca2+ influx mediated by TRPM7 is altered in ME/CFS patients relative to HCs. Further research to define the role of the TRPM7 channel-kinase in ME/CFS is therefore required to clarify the pathomechanism of this condition for diagnostic and therapeutic purposes."

Now I am understanding that the relationship between TRPM3 and TRPM7 is that TRPM3 channeling influx of Ca2+ is reduced by intracellular Mg, and TRPM7 is a Mg2+, Ca2+, and Zn2+ channel.

Transient Receptor Potential Melastatin (TRPM)7, essential for cellular magnesium homeostasis.

Silencing TRPM7 mimics the effects of low extracellular magnesium on human microvascular endothelial cells

We identify a binding site for highly potent and selective inhibitors and show that they act by stabilizing the TRPM7 closed state.

Remember that Zn activates NK cells.

 

[SWAlexander]

we still are on everything concerning ME/CFS

I do believe science conveniently blaming EBV, and avoiding questions outside the box.
Makes no sense to me, unless they have given up or hiding something.

 

[ruben]

I do believe science conveniently blaming EBV, and avoiding questions outside the box.
Makes no sense to me, unless they have given up or hiding something.

Could you just explain what you mean by hiding something?

 

[Wishful]

Allow me to disagree with this.

I didn't mean that no PWME have demyelination or that various disorders can't cause demyelination directly or indirectly. I meant that I hadn't seen any studies that show that the majority of PWME show significant demyelination. If demyelination was an essential part of ME, it would be included in the criteria. It wouldn't be a definite ME biomarker, since it is obviously not unique to ME.