Raghavan, P. R. | bioRxiv Science

bioRxiv2024

Metadichol(R) induced expression of the TLR family of receptors in PBMCs

Toll-like receptors (TLRs) are fundamental components of the innate immune system and function as the primary sensors of invading pathogens by recognizing prevalent microbial compounds. The expression of all ten transcription factors belonging to the TLR family (1-10), with the exception of TLR4, exhibited an inverted U-shaped reaction to metadichol, a nanoemulsion composed of long-chain alcohol, as determined by the Q-RT{square}PCR assay. The response pattern suggested that low, moderate, and high concentrations directly affect TLR expression. This may indicate a dual-phase or dose-dependent effect on the immune system regarding TLR regulation. Compounds targeting TLRs can stimulate or inhibit these receptors, thereby affecting the immune response. Adjusting immunological activation, crucial for therapeutic purposes in conditions such as inflammation, cancer, infection, allergies, and autoimmune diseases, requires an inverse U-shaped response. Currently, no single-molecule examples can elicit the activation of every Toll-like receptor (TLR). This study examined the expression levels of all ten Toll-like receptors (TLRs), MYD88, and the downstream genes IRAK4, TRAF3, and TRIF. Metadichol expresses all the 15 genes.

cell biology↗

bioRxiv2024

Metadichol induced expression of circadian clock transcription factors in human fibroblasts.

The circadian clock genes play a significant role in various aspects of health and disease, including sleep, metabolism, inflammation, and cancer. CRY1, BMAL1, PER1, PPARGC1A, and CLOCK are key circadian clock genes that govern the daily rhythms of diverse physiological processes in mammals. These genes create a feedback loop called a transcriptional-translational feedback loop (TTFL). In this loop, the heterodimer of CLOCK and BMAL1 stimulates the production of CRY1, PER1, and other clock genes. Moreover, the CRY1 and PER1 proteins suppressed the activity of CLOCK-BMAL1. PPARGC1A is a transcription factor that regulates the expression of clock genes and metabolic genes. Only a limited number of agonists are currently known to activate these genes. In this study, we showed that treatment with metadichol, a nanoemulsion of long-chain alcohols, significantly increased the expression of the CRY1, CLOCK, and PPARGC1A genes by 4-5-fold in human fibroblasts. Additionally, 100 ng of metadichol maintained the expression of the PER1 and BMAL1 genes, as confirmed by quantitative real-time polymerase chain reaction (Q-rt-PCR) data. The lack of significant changes in PER1 and BMAL1 expression suggested that metadichol does not directly affect these genes. However, since these genes are part of the core circadian clock machinery, their normal functioning is crucial for maintaining the circadian rhythm.

cell biology↗