@Maximalus no

@sunsunsun Wax moths? They don't even have neutrophils and I won't deep-dive into finding out how their hemolymphs specifically compare to human or mammalian neutrophils. I really do harbor strong apprehensions against the potential (mis)use of doxy on fungal infections. What I would much rather do is oral terbinafin + fluconazole. The terbinafin by itself is useless against many fungi species but allegedly it strongly inhibits expression of the fungal efflux pumps responsible for azole resistance! This still won't tackle activitiy in the biliary tract, though. I've done some more reading of publications on biliary / gallbladder candida / fungi. Fungi can be causes of calculous (lithiasic) or also acalculous cholecystitis with or without mixed bacterial infections (Escherichia coli, Enterococcus, Klebsiella, Enterobacter, Clostridia). Even in such rare and often fatal cases that happened to be documented, candidemia was rare despite frequent (almost always) fungal infection of other organs. https://pubmed.ncbi.nlm.nih.gov/8862389/ https://pubmed.ncbi.nlm.nih.gov/28703118/ https://pmc.ncbi.nlm.nih.gov/articles/PMC8764969/ https://pmc.ncbi.nlm.nih.gov/articles/PMC12338181/ https://pubmed.ncbi.nlm.nih.gov/24474028/ https://pubmed.ncbi.nlm.nih.gov/8207288/ I don't have visible gallbladder wall thickening or distention or an obviously, universally accepted liver disease (except for hepatomegaly) but if I had I sure as hell would want to insist on flucytosine, or flucytosine + i.v amphotericin B along with any broad-spectrum antibiotics and before mutilating surgeries they'd offer. Have looked more into berberine again, too. It's impossible to achieve its antimicrobial concentrations (at least 0.1mg/mL) systemically. Serum concentrations are about 0.5 - 16 ng/mL. I.e. 0.000005 mg/mL. Ridiculous! The berberine in practical doses of 500-1500mg will thus be acting mainly within the GI lumen in support of oral Ampho-B. Berberine has low absorption but some will spill over to reach the liver for extensive first-pass metabolism, yet probably not into biliary ducts.

Magnesium ratio for Ca:Mg is a nonsense as long you target the RDA for Ca 1000-1200 mg Ca. We’d better target the minimum amount, which is makes more sense. Why? The body is able to optimize the assimilation. As far as I’m concerned, I target: Ca: 800-850 mg. minimum 600 mg if other acid-base elements are correct. Mg: 300 mg. Not higher than 450 mg (Vit D). K: 3000 mg. Comment: Yes, Mg is useful. And so are MCTs from coconut. But before targeting ketosis for changing the microbiote, you’d better think twice and enlarge the view / the approach. You’ll probably get the same result with a 3-4 day fast and 600 K/cal diet, combined with a 16.8 diet. Useful info: https://mirzoune-ciboulette.forumactif.org/t2182-conversation-ia-n1-relation-calcium-mg-et-k-ajr-revisite-et-prevention-lithiase#30697 AI Conversation N° 1: Calcium, Mg, and K Relationship. Revised RDA and Kidney Stone Prevention. Context: Kidney stones. Excerpt (translated from French) Potassium intake (fine for getting oxalate crystals very brittle) and fiber (25-35 g/day). This is a key element. Personally, I aim for 3000 IU of K, 300 IU of Mg, and 800-850 IU of Ca (never below 600 mg for Ca). And don't bother me with the Mg/Ca ratio and aiming for 1200 mg of Ca. That's unrealistic… Acid-base balance is the determining factor. As long as PTH (0.5-3) isn't stimulated, things should be fine. This needs to be verified and nuanced (done on the given link with the “help” of AI). Potassium intake (very fragile oxalate crystals) and fiber (25-35 g/day). This is a key element. And if you're wondering how I use AI to avoid dodging the issue and thus influencing other readers, here's an explanatory link on my forum: https://mirzoune-ciboulette.forumactif.org/t8-presentation-de-luc-alias-nestor345#9 Excerpt: I use digital tools to confront my own statements and ensure the coherence of my summaries, but the 'spirit' of the advice comes from the literature I study and the feedback from my own community at Mirzoune et Ciboulette forum. I see my role as a translator or an analyst who reviews an interesting book or document. Having been a language teacher, my focus is on taking complex, dense information and making it structured and accessible for someone who’s lost or overwhelmed, who currently lacks the energy to digest a 200-page book. PS: I Know: We shouldn’t trust IA (…).

@alfredoolivas I don't think so because it's entirely possible to have a state of high dopamine and low prolactin. It might just act as a secondary mechanism apart from some other dopamine pathway solely to prevent a prolactin overload. The fact that it uses dopamine to prevent such an overload is an irrelevant implementation detail because it's not common you see people in a high dopamine but high prolactin state.

@alfredoolivas said in Are microdoses of mifeprestone the ultimate receptor level anti-glucorticoid?: it would likely occupy all progesteorone receptors, it's birth control, you can get it through online pharmacies I think. Then I don't think it's really worth the hassle. Id still be curious to hear how something like this feels and affects a person...

@CrumblingCookie said in Peaty uncoupler vs. Ozempic who wins ? New study.: If it enhances autophagy through AMPK it should not be limited to mitophagy but also cover xeno-autophagy Good point. That might make it helpful for fighting infections. @CrumblingCookie said in Peaty uncoupler vs. Ozempic who wins ? New study.: So a shift away from carbohydrates to FAO People often paint uncouplers as FAO-increasers. But they increase FAO and carb oxidation. The above article mentions it increasing TCA cycle, which can be fed by carbs and fat. It probably also depends on which tissues we are talking about. If you want to lean out your liver increasing FAO there is probably a good thing. @CrumblingCookie said in Peaty uncoupler vs. Ozempic who wins ? New study.: The MOA of BAM15 would then be a combination of inducing UCP and something along the line of metformin or berberine or spermidine (but lacking the Beclin-1 upregulation). (A comparison with resveratrol is less suitable since, although it lowers intracellular ATP through AMPK, I dare say its most important effect is through Sirt1) AMPK increases SIRT1. So BAM15 should do that, too.

@lobotomize yes but i think you'd have to be in somewhat decent shape to reap the benefits of cold showers. There is such a thing is cold resistance when it comes to thermogenesis and uncoupling. IIRC there was a study showing that grains of paradise were able to reverse that state in humans.

But astrocytes are known to be basically glycolytic, so klotho seems to me to be just reinforcing their mode of operation. Glycolysis is bad when it shouldn't happen there, but sometimes it's a better option than OXPHOS, even if it's inefficient. Just imagine how quickly oxygen would be depleted if the brain chose to do OXPHOS predominantly with fatty acids, as is the case with the heart, or how much superoxide would be generated...

@user73636 I just bought some royal jelly that arrived in a cold pack. It should be very good quality. Thanks for bringing this up. Have you tried it?

@user73636 Got it: Keeping to piña coladas, caipirinhas and pear nectar tequila or gin henceforth! Good call! Or do these ingredients indeed require a mutually synergistic blend?

@user73636 Di Bella method is very successful in many difficult cancers It usues somatostatin and melatonin. http://www.metododibella.org/it/Archivio-Newsletter.html https://www.metododibellaevidenzescientifiche.com/2022/05/03/mdb001-di-bella-et-al-2018/ Il sinergismo di somatostatina, melatonina, retinoidi, vitamin E, D3, C, inibitori prolattinici ed estrogenici, microdosi metronomiche di ciclofosfamide, ha incrementato sopravvivenza, risposte obiettive, performance status, in 297 casi di carcinomi del seno – The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer

@user73636 1 cup of chocolate chips has 15.691g of stearic acid. I think this fusion is just the result of fixing a deficiency. there are lots of foods with decent amounts of stearic acid in them.

Yes, these might interest you: Oxidation of hydrogen sulfide by Quinones: How polyphenols initiate their Cytoprotective effects ‘Antioxidant’ berries, anthocyanins, resveratrol and rosmarinic acid oxidize hydrogen sulfide to polysulfides and thiosulfate: A novel mechanism underlying their biological actions Alteration of the Gut Microbiome in Inflammatory Bowel Disease

Compounds that inhibit lactate overproduction are usually beneficial, but relying on oxaloacetate for this is not ideal. Pyruvate carboxylase is required for glutamine-independent growth of tumor cells (PC synthesizes oxaloacetate) In case of oxaloacetate supplementation, delivery is the first challenge because most of the dose is metabolized in the liver after absorption. For esterified forms, the fraction that reaches target cells is likely overestimated, especially when tissue circulation is poor. Malate dehydrogenase (MDH) interconverts malate and oxaloacetate, and this enzyme is also part of the malate-aspartate shuttle (MAS) that you mention. [image: 1772751634940-d34ce921-acea-4633-9653-639c96f9838f-image.png] ⠀(10.1101/cshperspect.a040543) The figure shows some potential concerns: Cytosolic NAD reoxidation by MDH can promote glycolysis, but without reliably improving mitochondrial metabolism for further oxidation. Increased demand for NAD+ relative to ATP drives aerobic glycolysis Extra oxaloacetate (OAA) may not convert into malate as expected. Aspartate is another component of the shuttle and is a reaction away from oxaloacetate (GOT/AST is bidirectional). [image: 1772751647814-4f7a93ec-7e75-4c6a-a1ad-ae54d314276c-image.png] ⠀(10.1016/j.ymgmr.2023.100967) An Essential Role of the Mitochondrial Electron Transport Chain in Cell Proliferation Is to Enable Aspartate Synthesis Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells Oxaloacetate enters mitochondria hydrogenated as malate. Recovering oxaloacetate on the mitochondrial side depends on sufficient NAD⁺ (also shown on the figure), which may be scarce and prioritized for other reactions, such as that of KGDHc. Recovery of oxaloacetate from malate in mitochondria doesn't guarantee its reaction with acetyl-CoA. It may instead support glutamate metabolism by accepting its amino group, yielding ketoglutarate for KGDHc (↻) or IDH (↺). One route doesn't exclude the other, as a fraction of ketoglutarate can undergo oxidative decarboxylation (releasing CO₂) and the other reductive carboxylation (incorporating CO₂), Supporting glutamate metabolism in forward function: Oxaloacetate + glutamate ←{GOT}→ Aspartate + Ketoglutarate Ketoglutarate –{KGDHc}→ Succinyl-CoA ←{STK}→ ATP + Succinate A portion of oxaloacetate-derived malate can also be converted to fumarate in reverse TCA cycle operation. Oxaloacetate → Malate → Fumarate → Succinate [image: 1772751671369-3224a3ed-9ba4-4586-bbab-57e75c344b76-image.png] ⠀(10.3389/fendo.2012.00022) This way, oxaloacetate helps to generate ketoglutarate to support mitochondrial fermentation and non-respiratory ATP synthesis with minimal oxidation. In addition, fumarate may be used as a substitute to deficient oxygen, accepting electrons from the respiratory chain sourced from ketoglutarate itself, dihydro-orotate, etc. (Oxaloacetate +) Glutamate → Ketoglutarate → Succinate ← Fumarate ← Oxaloacetate Succinate accumulation becomes comparable to lactate. Both metabolites are exported as fermentation end-products together with an extra H⁺, contributing to extracellular acidification. [image: 1772751690253-15d16b6b-0813-45e0-8bb1-7fecd96f1d33-image.png] ⠀(10.1080/17590914.2024.2422268) "Succinate-stabilized HIF-1a" reinforces PDHc inhibition, giving another reason not to assume that extra oxaloacetate and CoA release will serve PDHc, because they may just as well promote fatty acid oxidation. If oxaloacetate condenses with acetyl-CoA, that doesn't commit it oxidation either; oxaloacetate can serve as a carrier to export excess acetyl groups to support lipid synthesis. As for pyruvate and its multiple metabolic fates, even discounting lactate and oxaloacetate in this context, we can't assume that pyruvate routing to the chronically inhibited PDHc will prevail over supporting an upregulated pathway, such as in metabolizing abundant glutamate via GPT/ALT, which remains expressed outside the liver. Pyruvate + H⁺ + CoA + NAD⁺ –{PDHc}→ Acetyl-CoA + CO₂ + NADH + H⁺ Pyruvate + ⇈Glutamate ←{GPT}→ Alanine + Ketoglutarate This is another potential route that would supply ketoglutarate without depending on glutamate oxidation, sparing oxidative capacity to keep KGDHc running.