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sci / sci.engr / MWI technology

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o MWI technologyKay Lie

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Subject: MWI technology
From: Kay Lie
Newsgroups: sci.engr
Date: Wed, 26 Jul 2023 11:40 UTC
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Subject: MWI technology
From: liekay631@gmail.com (Kay Lie)
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Fisetin, a senolytic, is $22 per 10g on ebay, so creating variations on fisetin that are just as affordable or even more affordable could benefit even more people;
Aspartame: $40.96/Kg (ebay) is much like a two mer (unit) peptide, noting Pro-Gly favors transport to the brain, it is possible there are numerous two mer peptides, among 400 (20 amino acids times 20) variations, that localize at a variety of particular tissues; It is possible that attaching these two mer peptides to fisetin or another even a more affordable molecule could create really affordable, perhaps even greater potency per milligram senolytics with beneficial effects at numerous tissues. That also benefits longevity medicine worldwide.

Noting fisetin, which wikipedia mentions is sometimes called “5-Deoxyquercetin” is a phenol, it is possible other phenols are senolytics, a chlorinated phenol, possibly a variant on trichlorophenol or could be a senolytic that is 10 or 100 times more potent per mg, thus making a fisetin equivalent dose go to $2.20/10g or even $.22 per 10 grams; at an approximate 500mg daily senolytic fisetin equivalent dose (although it is possible it is actually 6 grams every 24 hours if the mouse compensation factor is ignored) that 500 mg is 11 cents a day (10 times potency) or possibly 1.1 cents a day (100 times potency).

Noting that quercetin is also a senolytic and has been published as being effective when combined with dasatinib the name version of fisetin that is Deoxyquercetin suggests the possibility of screening a library of the starting quercetin molecule could find molecular variants that have longevity and healthspan benefits; chloro and other halogenated quercetins, possibly where the halogen replaces the oxygen at the body of the mid-molecule carbon cycle could do something, it could be the distal parts of the molecule could have more effect (quercetin omits one -OH, so if fisetin is thought to be even more effective than quercetin then a halogen like Cl where the OH difference between fisetin and quercetin is could increase effectiveness further); Or, noting ethynylization makes estrogen and progesterone go from hundreds of milligrams to hundreds of micrograms to be an effective dose it is possible an ethynyl version of fisetin or quercetin, where one of the-OH is swapped out with an ethynyl could cause a senolytic variation on fisetin or quercetin that has 10 times, 100 times or even 1000 times less mg (or mcg) to be an effective senolytic dose and might localize at different tissues. If the ethynyl actually gets it to 1/1000 producing a few hundred or tens mcg dose then a longevity and healthspan increasing dose of senolytics could be less than 1/10 of a cent to make, and noting fisetin on ebay is $22/10g something 1000 times effectiveness is near 1/10 of a cent per dose, also that is just 3.2 cents for a month long treatment or 1.6 cents for a 14 day treatment that I think I read about. That affordability benefits longevity of humans globally.

Fisetin dose and treatment length variation, “Fisetin turned out surprisingly to be superior to other currently known senolytic compounds. The study concluded it would induce apoptosis (cell death) in 25-50% of senescent cells. The dose which the researchers used was 500 mg per day for five days for a 132lb / 60kg person so the dose needs to be adjusted to the individual persons weight.” so perhaps 700 mg a day for 14 days; also “Mayo human trials of fisetin. Dosage is 20 mg/kg/day for 2 consecutive days.” is 1.4 grams per day for two days, so possibly take 700 mg until 2.8 grams remain, then use the Mayo study dose for 48 hours. Also, Mayo Clinic: “100 mg/kg of fisetin in 60% Phosal 50 PG:30% PEG400:10% ethanol” is 7 grams per 24 hours. Phosal is Phosphatidylcholine Contents 25-75% with: Medium-Chain Triglycerides Sunflower Oil Safflower Oil Propylene Glycol; piperine may amplify fisetin potency: “It is claimed that taking 10 mg of BioPerine, a supplement that is reputed to magnify the effects and potency of flavenoids and other supplements, along with a dose of Fisetin will greatly increase its bio-availability.”, “In our last session of taking a massive dose (5 g) of Fisetin, my wife and I took 10 mg of BioPerine with each of ten 500 mg doses of Fisetin.. This did seem to produce some magnifying effect, because I experienced a mild side effect (vertigo) that I had not experienced with a previous large Fisetin dose.”

fisetin with DHA: https://www.fightaging.org/archives/2018/10/animal-data-shows-fisetin-to-be-a-surprisingly-effective-senolytic/ “The combination of the two agents was found to have a strong synergistic effect on inflammation. Effective ratios include without limitation those where fisetin is provided at a concentration of at least 5 μM, and where the ratio of DHA to fisetin may be at least about 1:2, 1:5, 1:10 or more". My add - is it synergy or fish oil increasing bioavailability?”
so 600 mg of fisetin would go with 3 grams of DHA, which could be beneficial as a lipid medium, 3 grams of DHA is about 30 fish oil capsules at the 10 times as much DHA as fisetin. The 2 days, or perhaps more at 1.4 grams of fisetin a day is again about 3 Grams DHA at a two to one DHA fisetin ratio.
Oral fisetin is much more optimal as a longevity technology because oral is convenient, notably though, “It has been shown that the fisetin nanoemulsion injected intravenously showed no significant difference in systemic exposure compared to free fisetin in mice, but when given intraperitoneally as compared to free fisetin, a 24-fold increase in the relative bioavailability of fisetin was found.”

piperine could heighten phenibut effectiveness and metformin effectiveness and antipsychotic effectiveness: “refer you to https://www.isotrope..com/bioperine/ . It says that: "P-glycoprotein is a protein the body uses to break down exogenous compounds found in the body. This protein inhibits the action of many medications, and also regulates the degree to which certain nutrients are absorbed by the body. This protein actively controls the permeability of the blood-brain barrier, which directly impacts the overall effects seen by many compounds such as curcumin—the active compound found in Turmeric. Piperine inhibits the action of this protein."

Perhaps piperine effects the permeability of the bodywide vascular epithelium as well, causing greater drug activity at numerous tissues and organs simultaneously. Fisetin dose frequency and plasma half life could benefit from a novel molecular form that is nonreacted at the liver, fisetin’s plasma half life is described at a paper as being a quarter hour, at 233 mg/Kg in mice, although it is possible the mouse adjustment factor also applies to plasma half life, so that would make a human plasma half life of 3 hours, which suggests 4 times a day daytime dosing. Then again the mouse compensation factor could just be some amount based on blood volume and liver volume, which I am not aware of.

I do not remember the moieties but I perceive that I have read about things that cause nonreactivity to liver enzymes at chemicals and drugs that could be made a part of senolytic molecules, Tyrosine sulfate is excreted through urine and, from what I read is without hepatic metabolism. I have no idea what attaching fisetin or dasatinib to a sulfate moeity would do; It is possible that just attaching fisetin to a molecule that has a few hundred hour plasma half life (although with all those -OHs on it it seems likely liver enzymes would modify those -OH even if one side of the molecule had some 200 hour plasma half life chemical like pimavanserin (an antipsychotic I am on) or a group like a sulfate that makes things like amino acids nonmetabolized; another plasma half life benefitting version: the Mayo clinic liposome version of fisetin, lengthy circulation with perhaps gradual liposomal bag coming apart and gradual release or also liposomal migration past the vascular epithelia to actual tissue cytes, skipping repeated hepatic passes (and metabolism) through the circulatory system.

Fisetin dose and plasma half life could benefit from that as plasma half life after IV administration is described at a paper as being a quarter hour, at 233 mg/Kg in mice, although it is possible the mouse adjustment factor also applies to plasma half life, so that would make a human plasma half life of 3 hours, which suggests 4 times a day daytime dosing. Then again the mouse’ interval equivalent compensation factor could just be some different amount based on blood volume and liver volume and amount of available liver enzymes, which I am not aware of.

Noting autophagy at cytes and organelles is there such a thing as autophagy of nonorganelle, possibly even nonprotein cytoplasm goop? I perceive at dermatocytes this is things like hyalonuric acid, so if hyalonuric acid has disintegration products then cycling it to get fresh goop could be beneficial, also it is my perception that the volume of cytogoop is large compared to the size of lysosomes so there might be a non lysosomal goop improvement mechanism at phenotypically young cytes, also what of cytogoop refreshingness at neurons?
Longevity technology: Some organisms like bacteria and possibly fungi like athlete’s foot fungi and yeast produce protein-lytic enzymes called proteases, it is possible that cytotransport of proteases to senolytic opportunities could cause sufficient dissolving of things at the cytoplasm like organelles to cause organism benefitting apoptosis. To quantify the effect at huamns and human tissue: note the number and ratio of nonoptimal cytes at things like surface dermis or vaginal or even cheek dermis; then have an antibiotic susceptible protease producing organism infect the tissue, which likely seems to then exude plasma like fluid and be gooey, then enumerate the percentage increase in young phenotype cytes after some number of hours of infection and then do organism infection termination with antibiotics; if the proteases are senolytic then although they are infected the remaining healing cytes would be youthful phenotype and be the cytotype that lives, and the tissue restored to youthful phenotype.
Also, if this is accomplished without bacteria, just using calibrated repeatable laser ablation of mouse dermal tissue, this would be a way to screen a library of hundreds or even thousands of proteases and other enzymes to find some that are medically actual senolytics, also, at tissue culture it would be possible to see if the dermal senolytics also had senolytic capability at completely different tissue like those found at depth in the body.
I think I read that some viruses code for proteases so the viruses can make tissue gooey, spreading the virus; engineering those viruses, or possibly breeding them to make senolytic proteases or other enzymes could make an internal to the body produced senolytic, possibly with some tissue localization, that has better coverage and puts less stress on the body than systemic or organ or tissue concentrated bacteria or fungi would.


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