interesting comment from Dr Younger:
"Thanks for bringing up that issue! There has been a ton of misinformation on "regular" prescription naltrexone, even among experts. If you look it up on Google, it will tell you that naltrexone is a racemic mixture of l- and d- forms. Any many, if not most, papers do the same. They are all wrong. If you pull up the CoA for manufactured naltrexone, you will see it has a -192 degree optical rotation. All commercial naltrexone is levo only. Levo hits both opioid and TLR4 receptors (among other things), while dextro only hits the TLR4 receptor. I don't know how to fix the misinformation online because now AI is pulling its info from incorrect sources. So it is almost impossible to get to the right source unless someone already knows what they are doing (e.g., accessing the manufacturer CoA's). - Jarred Younger"
https://www.youtube.com/watch?v=KpsK6RmqLNI&lc=Ugz8z9zuskpLiMGay-N4AaABAg.APdUyq5hqymAPdY5kV5qVu
078 - How I am going to fight brain inflammation | Jarred Younger, PhD
uploaded Nov 17, 2025
https://youtu.be/KpsK6RmqLNI
Dr. Younger shares his intention to manufacture and test dextro-naltrexone in a clinical trial.
😀
#naltrexone #LDN #DextroNaltrexone #neroinflammation #neuroscience #immunology #MECFS #TLR4
Repetitive transcranial magnetic stimulation alleviates glial activation through suppressing HMGB1/TLR4 pathway in a rat model of Parkinson’s disease [2023]
https://doi.org/10.1007/s11033-023-08561-8
"This study showed that rTMS might be a promising method for alleviating neuroinflammation in PD rat models, and the effects might be mediated through the downregulation of the HMGB1/TLR4 pathway."
Background Repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to be effective in Parkinson’s disease (PD), but whether rTMS treatment has a relieving effect on neuroinflammation remains to be investigated. In this article, we explored the effects of rTMS on forelimb use asymmetry and neuroinflammation-related mechanisms in a 6-hydroxydopamine (6-OHDA)-induced PD rat model. Methods and results Rats in the 6-OHDA+rTMS group received 10 Hz rTMS daily for 4 weeks. Behavioral tests (the cylinder test) were performed at the 3rd and 7th weeks after the operation. Astrocyte and microglia activation and protein levels of tyrosine hydroxylase(TH), high-mobility group box 1(HMGB1) and toll-like receptors 4(TLR4) were investigated by immunohistochemistry and Western blot analyses, respectively. After 4 weeks of treatment, forelimb use asymmetry was ameliorated in the 6-OHDA+rTMS group. Consistent with the behavioral tests, rTMS increased TH in the substantia nigra (SN) and the striatum of PD rats. High glial activation and HMGB1/TLR4 expression in the SN and the striatum were observed in the 6-OHDA group, while rTMS alleviated these changes. Conclusions This study showed that rTMS might be a promising method for alleviating neuroinflammation in PD rat models, and the effects might be mediated through the downregulation of the HMGB1/TLR4 pathway.
Makes me wonder if the relationship between asthma prevalence and latitude is is mediated by TLR4 activation, in addition to or instead of vitamin D levels.
Asthma Prevalence Associated with Geographical Latitude and Regional Insolation in the United States of America and Australia [2011]
https://doi.org/10.1371/journal.pone.0018492
Association between Recent Acetaminophen Use and Asthma: Modification by Polymorphism at TLR4 [2014]
https://synapse.koreamed.org/articles/1022548
Background It has been proposed that vitamin D deficiency may be responsible for an increase in the prevalence of allergic diseases and asthma worldwide. Human ability to generate physiologically required quantities of vitamin D through sun exposure is decreasing with increasing geographical latitude. Objectives Considering that vitamin D deficiency is usually due to lack of outdoor sun exposure, this study is designed to test the hypothesis that a higher prevalence of asthma should be expected at high relative to low geographical latitudes. Methods Linear regression analyses are performed on asthma prevalence in the U.S. adult population vs. geographical latitude, insolation, air temperature, and air pollution (PM2.5) for 97 major metropolitan/micropolitan statistical areas of the continental United States of America and on general population asthma prevalence vs. geographical latitude in eight metropolitan areas of Australia. Results A 10° change in geographical latitude from southern to northern regions of the Eastern Seaboard is associated with a 2% increase in adult asthma prevalence (p<0.001). Total insolation in winter months is almost as strong as latitude in its ability to explain the observed spatial variation in the prevalence of asthma (r2 = 0.43; p<0.001). Similar results are obtained using the Australian data (r2 = 0.73; p<0.01), suggesting a consistent association between the latitude/insolation and asthma prevalence worldwide. Conclusions The results of this study suggest that, as a known modulator of the immune response closely linked with the geographical latitude and erythemal UV irradiation, vitamin D may play an important role in the development/exacerbation of asthma.
Near Infrared Light Reduces Inflammation via TLR4 In Vitro [2022]
https://youtu.be/e6xj14QYsoc
video discusses this article:
Infrared light therapy relieves TLR-4 dependent hyper-inflammation of the type induced by COVID-19
https://pmc.ncbi.nlm.nih.gov/articles/PMC8451450/
"The inflammatory response was induced in cell cultures by LPS, followed by exposure to 720 nm LED light source at an intensity of 6 W/m2 for 10 min at 12-h intervals (see methods). ... At the end of the 48-h treatment period, cells were harvested and gene expression analysis performed. The results showed an approximately 50% reduction in gene expression of all of these markers in response to LED infrared exposure (Figure 4). ..."
Abstract Coronavirus disease 2019, induced by SARS-CoV-2 virus (severe acute respiratory syndrome-related coronavirus 2), has led to a huge negative impact on people’s health all around the globe, including in Ukraine. The potential effects of coronavirus infection on the course of osteoarthritis, one of the most widespread chronic degenerative joint illnesses, remains unclear. The aim of this work was to analyze the expression of COMP, TLR2, TLR4, and NFKB1 genes in synovial liquid cells as well as to establish the concentration of cytokines (IL-6, IL-8), TLR-2, and COMP in blood plasma of osteoarthritic patients that have had the SARS-CoV2 infection. The research included 75 men, aged from 45 to 55 years. The volunteers were divided into the following groups: the first group (n = 25) was conditionally healthy people, the second group (n = 25) was II–III degree knee joint osteoarthritis patients, and the third group consisted of 25 patients with II–III degree knee joint osteoarthritis after having had COVID-19. The expression levels of COMP, TLR2, TLR4, and NFKB1 genes in knee joint synovial liquid cells was measured by RT-qPCR. The concentration of IL-6, IL-8, TLR-2, and COMP was estimated with enzyme-linked immunosorbent assay. More significant decrease in the COMP gene expression in osteoarthritic patients that had COVID-19 was shown compared to the group with knee joint osteoarthritis alone on the background of more intensive COMP concentration increase in patients with osteoarthritis after SARS-CoV-2 infection. At the same time, the increase in expression levels of TLR2, TLR4, and NFKB1 was also detected as more evident in osteoarthritic patients after having COVID-19 disease if compared to the group of patients with knee joint osteoarthritis on the background of more substantial increase in IL-6, IL-8, and TLR-2 in osteoarthritic patients after having SARS-CoV-2 infection. Exacerbation of systemic inflammation due to the body’s response to viral invasion can cause such a pathological connection. The results indicate the intensification of destructive processes in the cells of the synovial fluid of patients with osteoarthritis after SARS-CoV-2 infection, which may indicate the risk of a more severe course of this disease.
A synthetic #TLR4 agonist significantly increases #humoral immune #responses and the protective ability of an #MDCK-cell-derived inactivated #H7N9 #vaccine in #mice, Arch Virol.: https://link.springer.com/article/10.1007/s00705-024-06082-8
Antigenically divergent H7N9 viruses pose a potential threat to public #health, with the poor #immunogenicity of candidate H7N9 vaccines demonstrated in clinical trials underscoring the urgent need for more-effective H7N9 vaccines.
Antigenically divergent H7N9 viruses pose a potential threat to public health, with the poor immunogenicity of candidate H7N9 vaccines demonstrated in clinical trials underscoring the urgent need for more-effective H7N9 vaccines. In the present study, mice were immunized with various doses of a suspended-MDCK-cell-derived inactivated H7N9 vaccine, which was based on a low-pathogenic H7N9 virus, to assess cross-reactive immunity and cross-protection against antigenically divergent H7N9 viruses. We found that the CRX-527 adjuvant, a synthetic TLR4 agonist, significantly enhanced the humoral immune responses of the suspended-MDCK-cell-derived H7N9 vaccine, with significant antigen-sparing and immune-enhancing effects, including robust virus-specific IgG, hemagglutination-inhibiting (HI), neuraminidase-inhibiting (NI), and virus-neutralizing (VN) antibody responses, which are crucial for protection against influenza virus infection. Moreover, the CRX-527-adjuvanted H7N9 vaccine also elicited cross-protective immunity and cross-protection against a highly pathogenic H7N9 virus with a single vaccination. Notably, NI and VN antibodies might play an important role in cross-protection against lethal influenza virus infections. This study showed that a synthetic TLR4 agonist adjuvant has a potent immunopotentiating effect, which might be considered worth further development as a means of increasing vaccine effectiveness.
Rhyothemis
Cytology and Genetics
Giuseppe Michieli