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https://www.selleckchem.com/products/ly333531.html g., YTHDF1/2/3, YTHDC1/2, IGF2BP1/2/3). Liver is the largest digestive and metabolic organ, and m6A modifications play unique roles in critical physiological hepatic functions and various liver diseases. This review focuses on the biological roles of m6A RNA methylation in lipid metabolism, viral hepatitis, nonalcoholic fatty liver disease, liver cancer, and tumor metastasis. In addition, we summarize the existing inhibitors targeting m6A regulators and discuss the potential of modulating m6A modifications as a therapeutic strategy. In the context of mechanically induced force transmission, the modification of the actin cytoskeleton through involvement of zyxin is an established concept. However, in cells of the periodontal ligament (PDL), which is physiologically subjected to intermittent mechanical forces, the force-responsive modulation of zyxin and the molecular key players, which orchestrate its cellular regulation, have not yet been elucidated. By employing indirect immunofluorescence and western blotting with different subcellular fractions, we show here in stretch force-exposed human PDL fibroblasts (hPDLFs) that (i) the zyxin protein is modulated, and (ii) its subcellular localization is altered. More importantly, using a pharmacological intervention approach, to inhibit the nuclear presence of the co-transcriptional activator yes-associated protein (YAP), we evidence for the first time that on the molecular level, the cellular abundance of zyxin, among the Thyrotrophic Embryonic Factor (TEF)-binding proteins, is regulated by YAP rather than TAZ. Our findings provide novel insights into the topic how cells of the periodontium and the periodontal ligament in particular respond and may adapt to mechanical forces, and first time identify YAP as the key player of the intracellular regulation of the mechano-sensor and mechano-transducer zyxin in hPDLFs. Moreover, the findings broaden the current knowledge on YAP
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