@LucH said in Toward a Better Understanding of Reactive Oxygen Species: @Amazoniac said in Toward a Better Understanding of Reactive Oxygen Species: The ROS linked to fat metabolism can arise partly from parallel effects, such as structural or functional perturbations and up-regulation of alternative ROS-producing enzymes (NOX, XO, COX, LOX, CYP2, etc.). I suppose that here we're mainly talking about excess PUFA loaded in adipocytes (AA cascade). When we stress or have a diet (fat loss). If we remain under 10 g PUFA/day, preferably 5-6 g, it would be OK. Edit: fine, the picture on ROS effects. (downloaded) ROS concentration & deleterious effects on cells. The next question is: What about when corn / soy food (from real food) is eaten, with LPS by-side load. Otherwise, it remains a theory. 1° In presence of ALA (thiol antioxidant) or a lipoprotection (A D3 K2 + vit E). 2° The same with aspirin or WWB. Parallel effects can also come from saturated fatty acids. Yet another example: Deleterious action of FA metabolites on ATP synthesis: possible link between lipotoxicity, mitochondrial dysfunction, and insulin resistance (Cyt c received fewer electrons overall, and pyruvate (oxaloacetate precursor) didn't normalize.) Impairing ATP synthesis limits electron consumption, which favors leakage from affected sites. On a related note, whether an imported fatty acid is saturated or not, the first stage of each β-oxidation cycle involves creating or dealing with an unsaturated intermediate (enoyl-CoA), and it's the hydrating reaction by enoyl-CoA hydratase* (ECH) that resolves the double bond by adding water, which also introduces the oxygen atoms that lack in fatty acids. *Synonym: unsaturated acyl-CoA hydratase This temporary double bond adds to any existing fatty acid double bonds outside of the segment being oxidized. After hydration, the NAD-dependent dehydrogenase (HADH) and the CoA-dependent thiolase (KAT) conclude a β-oxidation cycle. [image: 1770837140988-3a06059b-f0ac-452e-943e-35dceaf24dae-image.png] ⠀(10.1016/B978-0-12-382163-8.00022-0) Proper ECH activity relies on functional HADH and KAT, especially when the three enzymes form a supercomplex (the mitochondrial trifunctional protein, MTP) and work together to metabolize longer-chain fatty acids. Control of mitochondrial β-oxidation: sensitivity of the trifunctional protein to [NAD+]/[NADH] and [acetyl-CoA]/[CoA] Inhibitory effect of 3‐hydroxyacyl‐CoAs and other long‐chain fatty acid β‐oxidation intermediates on mitochondrial oxidative phosphorylation Pathophysiology of fatty acid oxidation disorders and resultant phenotypic variability Despite the experiment suggesting that inhibition is unlikely at healthy NADH/NAD⁺ and acetyl-CoA/CoA ratios, any factor that compromises one enzyme can affect the others. Local ratio perturbations or failure of backup systems may still lead intermediates to accumulate, including enoyl-CoA (the supercomplex's primary substrate). Given that some enzymes related to β-oxidation generate ROS, enoyl-CoA accumulation might place this unsaturated intermediate near ROS sources and start lipid peroxidation that then spreads to other lipids, such as cardiolipin. But it's a speculation.

@alfredoolivas the purpose of PT-141 is specifically to increase NO similarly to the PDE5 inhibitors like sildenafil/tadalafil, and it seems to be great at doing that. The benefit of melanotan II would be the added tanning which would be good if that's what you're looking for with the androgenicity/GR antagonism as a bonus. I personally have no need for that extra NO but in small quantities I think it wouldn't be a problem unless there's evidence otherwise. For the "symptom free cushing" thing it appears that if there are truly no symptoms, then the actual cause could be a faulty test where it's getting triggered by something else or had some manufacturing defect. Actually, the fact that the result was off the charts with no symptoms and that this was one case drastically increases the probability of a testing error. I am so curious about MT II's tanning and androgenicity that I'm thinking of grabbing some vials and trying something like 50ug/d. Anybody else thinking the same?

@Mauritio @mossy i had a cup of lemon balm tea after lunch yesterday and it was very calming, similar to chamomile but not sleepy-calm. My guess is that lemon balm is better for day time stress, and chamomile better for after dinner nighty night time! 🫖

Get some trees in your home! Shefflera are easy, ficus do well and ponytail palms!

@haidut ️

@DavidPS Thanks, there is also complementary story https://www.mdpi.com/1422-0067/26/17/8655 Ivermectin Binds to the Allosteric Site (Site 2) and Inhibits Allosteric Integrin Activation by TNF and Other Pro-Inflammatory Cytokines by Yoko K. Takada 1 andYoshikazu Takada 1,2,3,*ORCID 1 Department of Dermatology, University of California School of Medicine, Research III Suite 3300, 4645 Second Ave., Sacramento, CA 95817, USA 2 Department of Biochemistry and Molecular Medicine, University of California School of Medicine, Research III Suite 3300, 4645 Second Ave., Sacramento, CA 95817, USA 3 VA Northern California Health Care System, 150 Muir Road, Martinez, CA 94553, USA * Author to whom correspondence should be addressed. Int. J. Mol. Sci. 2025, 26(17), 8655; https://doi.org/10.3390/ijms26178655 Submission received: 1 August 2025 / Revised: 28 August 2025 / Accepted: 1 September 2025 / Published: 5 September 2025 (This article belongs to the Section Molecular Immunology) Abstract Ivermectin (IVM), a broad-spectrum anthelmintic agent, has anti-inflammatory properties, and affects cellular and humoral immune responses. We recently showed that multiple pro-inflammatory cytokines (e.g., FGF2, CCL5, CD40L) bind to the allosteric site (site 2) of integrins and activate them. 25-Hydroxycholesterol, a pro-inflammatory lipid mediator, is known to bind to site 2 and induce integrin activation and inflammatory signals (e.g., IL-6 and TNF secretion), suggesting that site 2 is critically involved in inflammation. We showed that two anti-inflammatory cytokines (FGF1 and NRG1) bind to site 2 and inhibit integrin activation by inflammatory cytokines. We hypothesized that ivermectin binds to site 2 and inhibits inflammatory signaling by pro-inflammatory cytokines. A docking simulation predicts that ivermectin binds to site 2. Ivermectin inhibits the integrin activation induced by inflammatory cytokines, suggesting that ivermectin is a site 2 antagonist. We showed that TNF, a major pro-inflammatory cytokine, binds to integrin site 2 and induces allosteric integrin activation like other pro-inflammatory cytokines, suggesting that site 2 binding and integrin activation is a potential mechanism of the pro-inflammatory action of these cytokines. Ivermectin suppressed the activation of soluble β3 integrins by TNF and other pro-inflammatory cytokines in a dose-dependent manner in cell-free conditions. Binding to site 2 and the inhibition of binding of inflammatory cytokines may be a potential mechanism of anti-inflammatory action of ivermectin.

@alfredoolivas I know that small amount are good but I do not pay attention so much to the "dosage of food." May that list is more handy https://www.nejm.org/doi/pdf/10.1056/NEJM199308053290619?articleTools=true

@Mauritio - Thanks From AI Effects of Lactobacillus reuteri Lactobacillus reuteri (L. reuteri) is a well-studied probiotic known for its beneficial effects on gut health and immune function. Research indicates that L. reuteri can influence the production of IL-10 in several ways: Immune Modulation: L. reuteri has been shown to enhance the production of IL-10, which helps to reduce inflammation and promote a balanced immune response. Gut Microbiota Interaction: By modulating gut microbiota composition, L. reuteri can create an environment that favors the production of IL-10, contributing to improved gut health and reduced inflammatory conditions. Clinical Studies: Some studies have reported that supplementation with L. reuteri leads to increased levels of IL-10, suggesting its potential role in managing inflammatory diseases. How does Lactobacillus reuteri affect immune function beyond IL-10 production? Lactobacillus reuteri enhances immune function by increasing phagocytic activity in macrophages and boosting the secretion of nitric oxide and prostaglandin E2, which are crucial for immune responses. It also produces antimicrobial molecules like reuterin, which helps inhibit pathogenic microorganisms, contributing to overall immune health.

https://www.youtube.com/watch?v=F_CLYkVSb6E