Walter, this is a fascinating summary. I appreciate the links to the articles.
Still recovering from Omega now 2.5 months post infection, I can attest to a frightening loss of appetite/energy/weight/quality of life during the acute phase. The most serious symptoms have been persistent headaches; I continue to lose weight despite working out and eating more healthy and hydrating more. I'm keeping up on my COVID recovery nutraceuticals, esp. those related to authophagy. While I don't think I suffer from the more commonly-known symptoms of long covid, I know "recovery" as conventionally understood may take longer than I expected.
See if adding Ginseng to your protocol helps w/ the weight loss.
1/ 2013 paper--Acidic polysaccahide of Panax Ginseng regulates the mitochondria/caspase-dependent pathway in radiation-induced damage to the jejunum in mice &
2/ 2022 paper- Ginseng, a promising Choice for Sars cov 2: A mini review
I have 5 more ginseng papers to look at, but the gist is ginseng interrupts the apoptosis going on and great repair mechanism for oxident-damage. Plus boosts mito energy. I think it might protect telomeres, as well.
Thank you for those references. I read the second paper, and it doesn't make ultimate conclusions, but the fact that 1B of Chinese consume ginseng and there are no negative info, means that at least it doesn't hurt.
I've start taking ginseng 1 week ago, and can't be 100% positive, my waves of inflammation become more controllable, and immune response become much sharper.
I know now for sure, that nicotine (2 mg gum 2-3 times a day, not before night time) gives me ability to do my job ( writing the code ), which means, that spike persists in the blood stream, and we are probably targeting nicotine receptors in the brain (ew, feels, like as non-biologist I don't have rights to pronounce such sophisticated terms...).
Almost the same, 3 rd month with long covid. The one thing I've noticed is a provoking role of physical exercises. I've stoped running first - that was the cause of the most bright events. And I'm going to fully stop making even short workouts during 2 weeks at least. I've lost a lot of weight, like you, but looking at my gastronomical preferences I also lost a lot of Iron (I eat beef liver every day as a necessity). Stay strong Kid, we doomed to survive, but we just don't know how to pass these times though )))
Very good points. Incidentally, I did some blood testing for my rheumatologist in the past few weeks (I have a preexisting autoimmune condition). CRP and ESR elevated over typical levels; RBC count way down. So there is still some "extra" inflammation occurring, probably due to the persistence of spike protein.
Ginseng...I'll add it to the bagful of supplements I take twice daily. Good grief.
BTW faith gets me through the day, every day. If not for that I don't know how I could do it.
Excuse me for being indiscreet, but did your long covid appear after vaccination? Could it be the Spike Protein in the vaccine that causes it? It is said that the 1st strain of Wuhan has disappeared. Today, Omicron is dominant. I wonder if there are still long covid...My husband is also immunocompromised... Polyarthritis. Thank you for your answers.
This is outside my wheelhouse but the exercise provoking sounds like the mitochondrial part of the injury. Just passing this on in case it is helpful. ...I am treated for a medication induced mitochondrial injury by a Functional Medicine MD. I had a great response to aResearched Nutritional product called ATP 360 and Liposomal Glutathione.
Mr Walter Chesnut, thank you for sharing all this information. I’ve been obsessively reading about all this horror of the last two years, & I really appreciate your info. Have you been in contact with Dr Sukharit Bhakdi? He seems like a wonderful person & doctor, & I believe he spoke of this endothelial damage very early on in the pandemic. The two of you should definitely consult one another. Best of luck to you! :)
I noticed that the linked articles pulled data from 2020. "What about OMICRON?!" I shouted inwardly, then began to read between the lines.
Rather than specific variants, though, I believe the point is that, regardless of the receptor binding domain portion of the spike protein [which I believe is what differentiates (sub)variants from each other], the spike protein exerts profound overall systemic effects—except in the case of my 19-year-old son, who bounced back after 36 hours and resumed surfing and all that. Apparently surfing the South Shore of O'ahu is strongly anti-inflammatory.
I think the big takeaway is that the spike protein attacks the entire body. It’s a multisystemic inflammatory daisy-cutter, eliciting all manner of autoimmune dysfunction impacting vital organs, including the brain, CNS, and peripheral nervous system; circulatory system, especially endothelium; metabolism; homeostasis between systems; mental state; and overall vitality.
You mention Metformin in another stack. My understanding is that Berberine has all the same benefits as Metformin and then some with no side effects. Is this correct? And what about a product like the endothelial protect supplements from life extension?
I need to catch up on this work, but did watch you this past 2 weeks. I may have a new connection for you to look at re: GAGs and Long Covid/amyloidosis. These articles are connected by fucoidan and its therapeutic features. Please take a look, let the info percolate in your brain. I got sensitized to fucoidans when researching what helped in radiation exposure after nuclear attack.
{PS: we 1st 'met' a long time ago on twitter when you just had a few followers...BTW, I am in Franklin County, VT.--thank you for your gifts of intelligence and dedication-God Bless)
Greetings Françoise: No problem re: discretion. Such questions are essential if intellectual honesty is to help in times such as ours.
I was never vaccinated; had the first (alpha) strain in April 2020; had Omicron June through July of this year. I'm still battling the effects of Omicron 11 weeks later! Rheumatoid arthritis certainly did not help me. I think that the RA and COVID have worked together to make life very difficult. In my case the RA was severe enough to send me into early retirement in 2019. Without wanting to overgeneralize, I think that significant or severe autoimmune conditions can put folks at a considerable disadvantage when COVID comes knocking.
In my opinion (not only based on my experience) any significant pre-existing autoimmune disorder (1) can greatly exacerbate COVID infection and (2) can become worse after COVID infection.
Vaccination (and repeated vaccination) can make things much worse. But that doesn't mean the battle is lost.
Whether from viral infection or from vaccination, the problem seems to be the distribution of spike protein throughout the body. I am amazed at how efficient the virus—and especially the vaccine—are at delivering that nasty spike protein to every tissue and organ...and how persistent the spike is.
There are numerous excellent reports on how the virus and spike protein interact with the immune system to upset immune homeostasis and start a civil war of autoimmunity (for example, IL-8 and TNF up regulation), and—for people who already have some sort of autoimmune condition—the spike protein pours gasoline on the autoimmune fire. The spike protein is a toxin and sets off an immune response throughout the body...almost as if by design (I didn't just write that, did I?).
On the other hand, my 19-year-old son bounced right back after a few days of COVID in June. A day and a half of fever (an immune/allergic reaction to spike)...then back to running, jumping and surfing. My 59-year-old spouse came down with Omicron on Monday, and last (Thursday) night her temps normalized. She's still exhausted. You'd have to know my wife to understand how profound COVID is—she's usually full of energy and NEVER sleeps during the day. Both my wife and son have been in excellent health.
COVID is a battle...for many, a protracted battle. I'm working on a better diet and taking vitamins and supplements, mainly directed at promoting autophagy and immune health, and scrubbing spike proteins out of my aching body.
Just for background understanding, I am not a MD. I'm just a retired PhD, but my focus for 40 years has been in research design and methodology. I know how research of all kinds is supposed to work, and have been following emerging knowledge on rheumatology since 2018 and COVID since the pandemic began. COVID-related research has been severely compromised by corruption, whether it is vaccine-related, alternative treatment-related, or just about anything else. Fortunately many brave people such as Mr. Chestnut swim against the current, share actual knowledge, and many folks are waking up to the global disaster that is COVID (and "COVID vaccination"). We're starting to see robust studies that punch through the peer review and editorial barriers. Numerous anecdotal accounts of how harmful the COVID shots have been are now being bolstered by irrefutable studies using broader data, and these studies are replicable.
Furthermore, and more relevant to your concerns, it appears that more and more "dots" with respect to the immunological effects of the virus and the shots are emerging, and these "dots" are being connected. We're coming to understand more about how these things interact and produce real-life effects for not just one or two people, but for larger categories of patients. We're seeing the same elucidation with respect to neurological, cardio-pulmonary, GI, oncological, and just about every other "-ological" field as well. That's very encouraging.
I wish you and your husband the very best. Don't give up—keep fighting and follow the light.
Wondrous Walter and Wonderful Community, Dr. Fleming believes that Aloxistatin, a cysteine protease inhibitor, for SARS2, was known all along ....I also found a three year old study on cysteine protease inhibitors for endothelial dysfunction for your perusal and commentary. MANY THANKS!
Dr. Richard Fleming: "We have now presented at two conferences in Florida in the last two days. The drug shown to work against coronaviruses (and other viruses) and to reverse prion diseases is E64d (Aloxistatin).You can now find 41 more published papers on http://FlemingMethod.com under published link"
Aloxistatin Aloxistatin is a drug which acts as a cysteine protease inhibitor and has anticoagulant effects. It is a synthetic analogue of E-64, a natural product derived from fungi. It was researched for the treatment of muscular dystrophy but was not successful in human clinical trials, though it has continued to be investigated for treatment of spinal cord injury, stroke and Alzheimer's disease. It also shows antiviral effects.Wikipedia
Can J Physiol Pharmacol . 2018 Feb;96(2):120-127. doi: 10.1139/cjpp-2017-0016. Epub 2017 Aug 30.The protease inhibitor E64d improves ox-LDL-induced endothelial dysfunction in human aortic endothelial cellsMin Chen 1, Lina Ren 2, Yanyan Meng 1, Liye Shi 2, Ling Chen 2, Bo Yu 3 4, Qianqian Wu 1, Guoxian Qi 2Affiliations expandPMID: 28854341 DOI: 10.1139/cjpp-2017-0016
AbstractOxidized low-density lipoprotein (ox-LDL)-induced endothelial dysfunction in human vascular endothelial cells contributes to the development of atherosclerosis. E64d, a cysteine protease inhibitor, blocks the elastolytic activity of cathepsin essential for vascular matrix remodeling and reduces neurovascular endothelial apoptosis. The objective of this study was to investigate the effects and the underling mechanisms of E64d on ox-LDL-induced endothelial dysfunction in human aortic endothelial cells (HAECs). HAECs were treated with various concentrations of ox-LDL (0-200 mg/L) for 24 h with or without E64d. The results showed that E64d attenuated ox-LDL-induced increase in soluble intercellular adhesion molecule-1 (sICAM-1) concentration and reduction in endothelial nitric oxide synthase (eNOS) expression, prevented ox-LDL-induced reduction in cell viability and migration ability of HAECs. E64d decreased the protein expression of cathepsin B (CTSB), Beclin 1, and microtubule-associated protein light chain 3 (LC3)-II, but not p62. LC3 puncta and autophagosome formation were also reduced by E64d in HAECs. Moreover, E64d decreased the production of MDA and increased the activity of SOD. The results showed that E64d ameliorated ox-LDL-induced endothelial dysfunction in HAECs.
Long time follower, one time contributor, many thanks for your continued efforts here.
If you have the time look up Caroline Pover on Twitter. She is suffering from post Vaxx, (long covid?), injury and is finding relief in blood letting in order to reduce her symptoms. Quite interesting and it may tie in with some of your hypothesis?
Again, THANK YOU! Excellent study that you ferreted out from the Sorbonne on the tumor microenvironment, particularly the importance of autophagy. Fascinating. Many thanks!
It has never been even a regular flu since 1995... We just did not noticed that. https://www.youtube.com/watch?v=9J8ocgBRcVM Here is a prototype of Kill Bill. Lady Snow Blood... ))) We'll stay strong, Jayne, right?
Walter, this is a fascinating summary. I appreciate the links to the articles.
Still recovering from Omega now 2.5 months post infection, I can attest to a frightening loss of appetite/energy/weight/quality of life during the acute phase. The most serious symptoms have been persistent headaches; I continue to lose weight despite working out and eating more healthy and hydrating more. I'm keeping up on my COVID recovery nutraceuticals, esp. those related to authophagy. While I don't think I suffer from the more commonly-known symptoms of long covid, I know "recovery" as conventionally understood may take longer than I expected.
I don't recommend COVID as a weight loss plan.
Thanks for making these connections!
See if adding Ginseng to your protocol helps w/ the weight loss.
1/ 2013 paper--Acidic polysaccahide of Panax Ginseng regulates the mitochondria/caspase-dependent pathway in radiation-induced damage to the jejunum in mice &
2/ 2022 paper- Ginseng, a promising Choice for Sars cov 2: A mini review
I have 5 more ginseng papers to look at, but the gist is ginseng interrupts the apoptosis going on and great repair mechanism for oxident-damage. Plus boosts mito energy. I think it might protect telomeres, as well.
Thank you for those references. I read the second paper, and it doesn't make ultimate conclusions, but the fact that 1B of Chinese consume ginseng and there are no negative info, means that at least it doesn't hurt.
I've start taking ginseng 1 week ago, and can't be 100% positive, my waves of inflammation become more controllable, and immune response become much sharper.
Thank you!
"Testing NAD+ repletion therapy in cachectic mice revealed that NAD+ precursor, vitamin B3 niacin, efficiently corrected tissue NAD+ levels, improved mitochondrial metabolism and ameliorated cancer- and chemotherapy-induced cachexia."
NAD+ repletion with niacin counteracts cancer cachexia
https://www.biorxiv.org/content/10.1101/2022.07.06.499010v1
Add some natural d-alpha tocopherol and selenium yeast to the flush niacin, and you're gravy!
Tried ivermectin in case you have lingering spike in your tissues?
I take ivermectin twice a day, by 10 mg. I believe it helps with spike protein which might be exposed in the blood stream and serum (maybe) but the source stays somewhere else, and not achievable to interventions. https://www.darkdaily.com/2022/08/31/researchers-in-boston-find-covid-19-spike-protein-lingers-in-long-covid-19-patients/
I know now for sure, that nicotine (2 mg gum 2-3 times a day, not before night time) gives me ability to do my job ( writing the code ), which means, that spike persists in the blood stream, and we are probably targeting nicotine receptors in the brain (ew, feels, like as non-biologist I don't have rights to pronounce such sophisticated terms...).
Nicotine's benefit is from its oxidation upon heating to nicotinic acid aka (flush) niacin
"Testing NAD+ repletion therapy in cachectic mice revealed that NAD+ precursor, vitamin B3 niacin, efficiently corrected tissue NAD+ levels, improved mitochondrial metabolism and ameliorated cancer- and chemotherapy-induced cachexia."
NAD+ repletion with niacin counteracts cancer cachexia
https://www.biorxiv.org/content/10.1101/2022.07.06.499010v1
Add some natural d-alpha tocopherol and selenium yeast to the flush niacin, and you're gravy!
"Testing NAD+ repletion therapy in cachectic mice revealed that NAD+ precursor, vitamin B3 niacin, efficiently corrected tissue NAD+ levels, improved mitochondrial metabolism and ameliorated cancer- and chemotherapy-induced cachexia."
NAD+ repletion with niacin counteracts cancer cachexia
https://www.biorxiv.org/content/10.1101/2022.07.06.499010v1
Add some natural d-alpha tocopherol and selenium yeast to the flush niacin, and you're gravy!
Very promising study, thank you!
And I started experiments with apple pectin... We can't be sure that there is a singe reservoir of infection.
Interesting about the nicotine!
Nicotine's benefit is from its oxidation upon heating to nicotinic acid aka (flush) niacin
"Testing NAD+ repletion therapy in cachectic mice revealed that NAD+ precursor, vitamin B3 niacin, efficiently corrected tissue NAD+ levels, improved mitochondrial metabolism and ameliorated cancer- and chemotherapy-induced cachexia."
NAD+ repletion with niacin counteracts cancer cachexia
https://www.biorxiv.org/content/10.1101/2022.07.06.499010v1
Add some natural d-alpha tocopherol and selenium yeast to the flush niacin, and you're gravy!
Almost the same, 3 rd month with long covid. The one thing I've noticed is a provoking role of physical exercises. I've stoped running first - that was the cause of the most bright events. And I'm going to fully stop making even short workouts during 2 weeks at least. I've lost a lot of weight, like you, but looking at my gastronomical preferences I also lost a lot of Iron (I eat beef liver every day as a necessity). Stay strong Kid, we doomed to survive, but we just don't know how to pass these times though )))
Very good points. Incidentally, I did some blood testing for my rheumatologist in the past few weeks (I have a preexisting autoimmune condition). CRP and ESR elevated over typical levels; RBC count way down. So there is still some "extra" inflammation occurring, probably due to the persistence of spike protein.
Ginseng...I'll add it to the bagful of supplements I take twice daily. Good grief.
BTW faith gets me through the day, every day. If not for that I don't know how I could do it.
Excuse me for being indiscreet, but did your long covid appear after vaccination? Could it be the Spike Protein in the vaccine that causes it? It is said that the 1st strain of Wuhan has disappeared. Today, Omicron is dominant. I wonder if there are still long covid...My husband is also immunocompromised... Polyarthritis. Thank you for your answers.
This is outside my wheelhouse but the exercise provoking sounds like the mitochondrial part of the injury. Just passing this on in case it is helpful. ...I am treated for a medication induced mitochondrial injury by a Functional Medicine MD. I had a great response to aResearched Nutritional product called ATP 360 and Liposomal Glutathione.
"Testing NAD+ repletion therapy in cachectic mice revealed that NAD+ precursor, vitamin B3 niacin, efficiently corrected tissue NAD+ levels, improved mitochondrial metabolism and ameliorated cancer- and chemotherapy-induced cachexia."
NAD+ repletion with niacin counteracts cancer cachexia
https://www.biorxiv.org/content/10.1101/2022.07.06.499010v1
Add some natural d-alpha tocopherol and selenium yeast to the flush niacin, and you're gravy!
Mr Walter Chesnut, thank you for sharing all this information. I’ve been obsessively reading about all this horror of the last two years, & I really appreciate your info. Have you been in contact with Dr Sukharit Bhakdi? He seems like a wonderful person & doctor, & I believe he spoke of this endothelial damage very early on in the pandemic. The two of you should definitely consult one another. Best of luck to you! :)
thank you Walter as always. you are on the right path all seems to fit and connect together.
Thankyou mr Chestnut. Appreciate your work of informing us very much.
Hep C?
I have not registered that C19 caused Hep C.
Or did C19 weakened the immune systems and which allowed the existing dormant Hep C to reinvigorate?
I noticed that the linked articles pulled data from 2020. "What about OMICRON?!" I shouted inwardly, then began to read between the lines.
Rather than specific variants, though, I believe the point is that, regardless of the receptor binding domain portion of the spike protein [which I believe is what differentiates (sub)variants from each other], the spike protein exerts profound overall systemic effects—except in the case of my 19-year-old son, who bounced back after 36 hours and resumed surfing and all that. Apparently surfing the South Shore of O'ahu is strongly anti-inflammatory.
I think the big takeaway is that the spike protein attacks the entire body. It’s a multisystemic inflammatory daisy-cutter, eliciting all manner of autoimmune dysfunction impacting vital organs, including the brain, CNS, and peripheral nervous system; circulatory system, especially endothelium; metabolism; homeostasis between systems; mental state; and overall vitality.
You mention Metformin in another stack. My understanding is that Berberine has all the same benefits as Metformin and then some with no side effects. Is this correct? And what about a product like the endothelial protect supplements from life extension?
"Testing NAD+ repletion therapy in cachectic mice revealed that NAD+ precursor, vitamin B3 niacin, efficiently corrected tissue NAD+ levels, improved mitochondrial metabolism and ameliorated cancer- and chemotherapy-induced cachexia."
NAD+ repletion with niacin counteracts cancer cachexia
https://www.biorxiv.org/content/10.1101/2022.07.06.499010v1
Add some natural d-alpha tocopherol and selenium yeast to the flush niacin, and you're gravy!
I need to catch up on this work, but did watch you this past 2 weeks. I may have a new connection for you to look at re: GAGs and Long Covid/amyloidosis. These articles are connected by fucoidan and its therapeutic features. Please take a look, let the info percolate in your brain. I got sensitized to fucoidans when researching what helped in radiation exposure after nuclear attack.
https://pubs.acs.org/doi/10.1021/acsinfecdis.9b00425
&
https://www.nature.com/articles/s41421-020-00192-8
{PS: we 1st 'met' a long time ago on twitter when you just had a few followers...BTW, I am in Franklin County, VT.--thank you for your gifts of intelligence and dedication-God Bless)
"Testing NAD+ repletion therapy in cachectic mice revealed that NAD+ precursor, vitamin B3 niacin, efficiently corrected tissue NAD+ levels, improved mitochondrial metabolism and ameliorated cancer- and chemotherapy-induced cachexia."
NAD+ repletion with niacin counteracts cancer cachexia
https://www.biorxiv.org/content/10.1101/2022.07.06.499010v1
Add some natural d-alpha tocopherol and selenium yeast to the flush niacin, and you're gravy!
Brain damage due to small blood vessel blockage -- see this tweet made by my dog
https://twitter.com/TotallyCanc3l3d/status/1569322032562671617
Greetings Françoise: No problem re: discretion. Such questions are essential if intellectual honesty is to help in times such as ours.
I was never vaccinated; had the first (alpha) strain in April 2020; had Omicron June through July of this year. I'm still battling the effects of Omicron 11 weeks later! Rheumatoid arthritis certainly did not help me. I think that the RA and COVID have worked together to make life very difficult. In my case the RA was severe enough to send me into early retirement in 2019. Without wanting to overgeneralize, I think that significant or severe autoimmune conditions can put folks at a considerable disadvantage when COVID comes knocking.
In my opinion (not only based on my experience) any significant pre-existing autoimmune disorder (1) can greatly exacerbate COVID infection and (2) can become worse after COVID infection.
Vaccination (and repeated vaccination) can make things much worse. But that doesn't mean the battle is lost.
Whether from viral infection or from vaccination, the problem seems to be the distribution of spike protein throughout the body. I am amazed at how efficient the virus—and especially the vaccine—are at delivering that nasty spike protein to every tissue and organ...and how persistent the spike is.
There are numerous excellent reports on how the virus and spike protein interact with the immune system to upset immune homeostasis and start a civil war of autoimmunity (for example, IL-8 and TNF up regulation), and—for people who already have some sort of autoimmune condition—the spike protein pours gasoline on the autoimmune fire. The spike protein is a toxin and sets off an immune response throughout the body...almost as if by design (I didn't just write that, did I?).
On the other hand, my 19-year-old son bounced right back after a few days of COVID in June. A day and a half of fever (an immune/allergic reaction to spike)...then back to running, jumping and surfing. My 59-year-old spouse came down with Omicron on Monday, and last (Thursday) night her temps normalized. She's still exhausted. You'd have to know my wife to understand how profound COVID is—she's usually full of energy and NEVER sleeps during the day. Both my wife and son have been in excellent health.
COVID is a battle...for many, a protracted battle. I'm working on a better diet and taking vitamins and supplements, mainly directed at promoting autophagy and immune health, and scrubbing spike proteins out of my aching body.
Just for background understanding, I am not a MD. I'm just a retired PhD, but my focus for 40 years has been in research design and methodology. I know how research of all kinds is supposed to work, and have been following emerging knowledge on rheumatology since 2018 and COVID since the pandemic began. COVID-related research has been severely compromised by corruption, whether it is vaccine-related, alternative treatment-related, or just about anything else. Fortunately many brave people such as Mr. Chestnut swim against the current, share actual knowledge, and many folks are waking up to the global disaster that is COVID (and "COVID vaccination"). We're starting to see robust studies that punch through the peer review and editorial barriers. Numerous anecdotal accounts of how harmful the COVID shots have been are now being bolstered by irrefutable studies using broader data, and these studies are replicable.
Furthermore, and more relevant to your concerns, it appears that more and more "dots" with respect to the immunological effects of the virus and the shots are emerging, and these "dots" are being connected. We're coming to understand more about how these things interact and produce real-life effects for not just one or two people, but for larger categories of patients. We're seeing the same elucidation with respect to neurological, cardio-pulmonary, GI, oncological, and just about every other "-ological" field as well. That's very encouraging.
I wish you and your husband the very best. Don't give up—keep fighting and follow the light.
"Testing NAD+ repletion therapy in cachectic mice revealed that NAD+ precursor, vitamin B3 niacin, efficiently corrected tissue NAD+ levels, improved mitochondrial metabolism and ameliorated cancer- and chemotherapy-induced cachexia."
NAD+ repletion with niacin counteracts cancer cachexia
https://www.biorxiv.org/content/10.1101/2022.07.06.499010v1
Add some natural d-alpha tocopherol and selenium yeast to the flush niacin, and you're gravy!
Wondrous Walter and Wonderful Community, Dr. Fleming believes that Aloxistatin, a cysteine protease inhibitor, for SARS2, was known all along ....I also found a three year old study on cysteine protease inhibitors for endothelial dysfunction for your perusal and commentary. MANY THANKS!
Dr. Richard Fleming: "We have now presented at two conferences in Florida in the last two days. The drug shown to work against coronaviruses (and other viruses) and to reverse prion diseases is E64d (Aloxistatin).You can now find 41 more published papers on http://FlemingMethod.com under published link"
Aloxistatin Aloxistatin is a drug which acts as a cysteine protease inhibitor and has anticoagulant effects. It is a synthetic analogue of E-64, a natural product derived from fungi. It was researched for the treatment of muscular dystrophy but was not successful in human clinical trials, though it has continued to be investigated for treatment of spinal cord injury, stroke and Alzheimer's disease. It also shows antiviral effects.Wikipedia
Can J Physiol Pharmacol . 2018 Feb;96(2):120-127. doi: 10.1139/cjpp-2017-0016. Epub 2017 Aug 30.The protease inhibitor E64d improves ox-LDL-induced endothelial dysfunction in human aortic endothelial cellsMin Chen 1, Lina Ren 2, Yanyan Meng 1, Liye Shi 2, Ling Chen 2, Bo Yu 3 4, Qianqian Wu 1, Guoxian Qi 2Affiliations expandPMID: 28854341 DOI: 10.1139/cjpp-2017-0016
AbstractOxidized low-density lipoprotein (ox-LDL)-induced endothelial dysfunction in human vascular endothelial cells contributes to the development of atherosclerosis. E64d, a cysteine protease inhibitor, blocks the elastolytic activity of cathepsin essential for vascular matrix remodeling and reduces neurovascular endothelial apoptosis. The objective of this study was to investigate the effects and the underling mechanisms of E64d on ox-LDL-induced endothelial dysfunction in human aortic endothelial cells (HAECs). HAECs were treated with various concentrations of ox-LDL (0-200 mg/L) for 24 h with or without E64d. The results showed that E64d attenuated ox-LDL-induced increase in soluble intercellular adhesion molecule-1 (sICAM-1) concentration and reduction in endothelial nitric oxide synthase (eNOS) expression, prevented ox-LDL-induced reduction in cell viability and migration ability of HAECs. E64d decreased the protein expression of cathepsin B (CTSB), Beclin 1, and microtubule-associated protein light chain 3 (LC3)-II, but not p62. LC3 puncta and autophagosome formation were also reduced by E64d in HAECs. Moreover, E64d decreased the production of MDA and increased the activity of SOD. The results showed that E64d ameliorated ox-LDL-induced endothelial dysfunction in HAECs.
"Testing NAD+ repletion therapy in cachectic mice revealed that NAD+ precursor, vitamin B3 niacin, efficiently corrected tissue NAD+ levels, improved mitochondrial metabolism and ameliorated cancer- and chemotherapy-induced cachexia."
NAD+ repletion with niacin counteracts cancer cachexia
https://www.biorxiv.org/content/10.1101/2022.07.06.499010v1
Add some natural d-alpha tocopherol and selenium yeast to the flush niacin, and you're gravy!
Good afternoon Walter,
Long time follower, one time contributor, many thanks for your continued efforts here.
If you have the time look up Caroline Pover on Twitter. She is suffering from post Vaxx, (long covid?), injury and is finding relief in blood letting in order to reduce her symptoms. Quite interesting and it may tie in with some of your hypothesis?
Keep fighting the good fight.
https://twitter.com/CarolinePover/status/1567236998678593537
Again, THANK YOU! Excellent study that you ferreted out from the Sorbonne on the tumor microenvironment, particularly the importance of autophagy. Fascinating. Many thanks!
https://hal.sorbonne-universite.fr/hal-03148595/document
It has never been even a regular flu since 1995... We just did not noticed that. https://www.youtube.com/watch?v=9J8ocgBRcVM Here is a prototype of Kill Bill. Lady Snow Blood... ))) We'll stay strong, Jayne, right?