9 replies to this topic

[Kalliste]

Another interesting paper on hydrated fullerenes.

http://www.ncbi.nlm....pubmed/24646197

 

The effects of hydrated C(60) fullerene on gene expression profile of TRPM2 and TRPM7 in hyperhomocysteinemic mice.

Etem EO¹, Bal R, Akağaç AE, Kuloglu T, Tuzcu M, Andrievsky GV, Buran I, Nedzvetsky VS, Baydas G.

Author information

• ¹Department of Medical Biology, Faculty of Medicine, Firat University , Elazig , Turkey .

Abstract

Abstract Background: Hyperhomocysteinemia (HHcy) is associated with neurodegenerative diseases. Transient receptor potential melastatin (TRPM2) and TRPM7 channels may be activated by oxidative stress. Hydrated C(60) fullerene (C(60)HyFn) have recently gained considerable attention as promising candidates for neurodegenerative states. We aimed to examine the effects on TRPM2 and TRPM7 gene expression of C(60)HyFn due to marked antioxidant activity in HHcy mice.

METHODS:

C57BL/6 J. mice were divided into four groups: (1) Control group, (2) HHcy, (3) HHcy + C(60)HyFn-treated group and (4) C(60)HyFn-treated group. TRPM2 and TRPM7 gene expression in brains of mice were detected by real-time PCR, Western blotting and immunohistochemistry. Apoptosis in brain were assessed by TUNEL staining.

RESULTS:

mRNA expression levels of TRPM2 were significantly increased in HHcy group compared to the control group. C(60)HyFn administration significantly decreased serum levels of homocysteine and TRPM2 mRNA levels in HHcy + C(60)HyFn group. Whereas, HHcy-treatment and C(60)HyFn administration did not change the expression of TRPM7.

CONCLUSION:

Administration of C(60)HyFn in HHcy mice significantly reduces serum homocysteine level, neuronal apoptosis and expression level of TRPM2 gene. Increased expression level of TRPM2 induced by oxidative stress might be involved in the ethiopathogenesis of HHcy related neurologic diseases.

 

 

 

[resveratrol_guy]

Interesting study. "significantly reduces... neuronal apoptosis". They make it sound as though neuronal apoptosis is somehow downregulated, when in fact this might mean that less neuronal apoptosis was observed simply because fewer neurons became sufficiently damaged to induce apoptosis. This is not a trivial distinction: preventing corrupt neurons from committing suicide might be carcinogenic, especially if it affects other cell types similarly; whereas preventing neurons from becoming sufficiently corrupt as to induce apoptosis would obviously be a good thing.

 

Judging from the lowered homocysteine, it sounds like the latter is more accurate. But I raise the point just because other members may know more about this, bearing in mind that C(60)HyFn may or may not relate to c60oo. (BTW I'm surprised that no one seems to have made a mass spectrometric attempt to determine the molecular structure of c60oo. Maybe there are too many impurities to get a clue, but they managed to find beta sitosterol (sp?) and its HDL effects, so there's hope.)

 

[niner]

BTW I'm surprised that no one seems to have made a mass spectrometric attempt to determine the molecular structure of c60oo. Maybe there are too many impurities to get a clue [...]

It's kind of a hard problem. Olive oil has a mix of fatty acids that vary from batch to batch. (It may be the case that c60 reacts primarily with the oleic acid fraction) The polyphenol content varies as well. (C60 probably doesn't react with the polyphenols) To make matters more interesting, the c60 reacts with oxygen during the usual process of synthesis, initially forming epoxides but probably ending up as hydroxyls. Depending on the degree of oxygen exposure, there will be a spectrum of -OH substituted c60, which are in turn attached to one or more fatty acids. I found that a synthesis process that largely excluded oxygen removed the anti-eczema effect, which was recovered when I synthesized a new batch holding all reagents constant but admitting O2 into the process. Thus we can isolate the immunomodulatory effects of c60oo from the mitochondrial effects, and associate it with a difference in the composition of the active products. This is all to say that 1) it's complicated, and 2) I'd really like to see someone do such an analysis. It would probably involve more than MS analysis in the end, depending on how precisely you wanted to characterize the active agents.

[niner]

BTW, has Andrievsky's HyFn ever been run through the mass spec? I have a suspicion that it also turns into a polyhydroxy compound.

[resveratrol_guy]

 

BTW I'm surprised that no one seems to have made a mass spectrometric attempt to determine the molecular structure of c60oo. Maybe there are too many impurities to get a clue [...]

It's kind of a hard problem. Olive oil has a mix of fatty acids that vary from batch to batch. (It may be the case that c60 reacts primarily with the oleic acid fraction) The polyphenol content varies as well. (C60 probably doesn't react with the polyphenols) To make matters more interesting, the c60 reacts with oxygen during the usual process of synthesis, initially forming epoxides but probably ending up as hydroxyls. Depending on the degree of oxygen exposure, there will be a spectrum of -OH substituted c60, which are in turn attached to one or more fatty acids. I found that a synthesis process that largely excluded oxygen removed the anti-eczema effect, which was recovered when I synthesized a new batch holding all reagents constant but admitting O2 into the process. Thus we can isolate the immunomodulatory effects of c60oo from the mitochondrial effects, and associate it with a difference in the composition of the active products. This is all to say that 1) it's complicated, and 2) I'd really like to see someone do such an analysis. It would probably involve more than MS analysis in the end, depending on how precisely you wanted to characterize the active agents.

 

 

So you implicitly invented a shortcut to solving at least the mitochondrial problem: we could take a small tissue sample from a heavy c60oo user, and extract the mitochrondria with nanotweezers or size-targetted nanofiltration (I assume this is feasible), then pulverize them (gently) and use an electron microscope to observe the C60 compounds -- not even necessarily a mass spec. As in: "Electron micrographs depicted agglomeration with a heterogeneous distribution of the fullerenols in the culture medium," which at least confirms the availability of sufficient resolution to do this. (https://www.ncbi.nlm...cles/PMC3217115 which is an interesting C60(OH)n toxicology analysis in its own right)

 

Short of that, then if what you say is accurate, we could make some headway by doing a mass spec of C60oo made in normal and hypoxic environments, the difference being a superset of the molecules which result in your eczema effects (and presumably other manifestations of inflammation).

 

It never occurred to me that there might be a plurality of C60 adducts with complementary or orthogonal benefits here. Good point.

 

Hopefully there are some PhD students lurking who might make a name for themselves by discovering the active ingredients in c60oo. This would be more than just academically satisfying; one can easily imagine pharmaceutical derivatives thereof, for example, to protect trauma patients from hypoxia.

[GVA]

BTW, has Andrievsky's HyFn ever been run through the mass spec? I have a suspicion that it also turns into a polyhydroxy compound.

Before the beginning of discussion of these statements.

 

Dear Fullerene, Happy Birthday to you! (since September, 4th, 1985).
Nice!

On behalf of my colleagues,

Grigoriy Andrievsky


Director of Science, PhD.
"Institute of Physiological Active Compounds" LLC.
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http://www.ipacom.com (!!!)
http://www.c60water.com

[Kalliste]

What?

[APBT]

FULL TEXT of:  The effects of hydrated C(60) fullerene on gene expression profile of TRPM2 and TRPM7 in hyperhomocysteinemic mice

[GVA]

What?

 

It is supposed, including Google, that day of fullerenes discovery and their Birthday is on September, 4, 1985

[GVA]

BTW, has Andrievsky's HyFn ever been run through the mass spec? I have a suspicion that it also turns into a polyhydroxy compound.

 

But, what is known about some ways of metabolism of so-called С60 adducts with unsaturated fatty acids in C60OO? (some recent paper of Cataldo on http://dx.doi.org/10...83X.2012.654532 and http://dx.doi.org/10...lip.2010.03.004). Whether they can turn into some polyhydroxy compound? Who knows now?

But what is the Mass Spec (see attached pdf-file at this post), NMR-, UV-Vis-, IR-, Luminescence- spectra, TEM-, STM- images, Light and Neutron Scattering, etc. of C60FWS – water solutions of Hydrated C60 Fullerene (C60HyFn) – such it can be possible to find in open full texts of articles on: https://www.research...sky?ev=hdr_xprf , and also in pdf-Presentation:

“Hydrated C60 fullerene: some most important physical-chemical and biological properties” on http://ipacom.com/in...en/research/105 (see, particularly, slides # 21-30).

In addition, it would be possible to mention that at this forum there are more earlier threads with discussion about HyFn:

C60/OO positive bioactivity relates to Hydrated Fullerene (HyFn) formation (http://www.longecity...hyfn-formation/);

TO THE QUESTION WHAT IS ACTUALLY THE ACTIVE PRINCIPLE IN C60_OO (http://www.longecity...iple-in-c60-oo/);

Hydrated Fullerene - HYFN (http://www.longecity...fullerene-hyfn/).

 

 ON THE PRODUCTION OF AN AQUEOUS COLLOIDAL SOLUTION OF FULLERENES (ChemComm_1995).pdf   201.1KB   7 downloads

Edited by GVA, 09 September 2014 - 12:24 AM.