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Decline of transcription factor FoxN1, which predominantly regulates thymic epithelial cell (TEC) differentiation and homeostasis lifelong, is demonstrated to be casually related to age-related thymic involution. Whereas, a global role of microRNAs (miRNAs) has also been demonstrated to control and maintain TEC-constituting thymic microenvironment and to be changed in expression profile in the aged thymus. Therefore, it is urgently necessary to build knowledge regarding whether and which miRNAs regulate FoxN1 gene in the aged thymus. We primarily compared changes in miRNA expression profile between young and aged murine TECs with Mus musculus miRBase-V20 arrays (containing 1892 unique probes), and clearly identified and validated that at least one miRNA, miR-125a-5p, was increased in aged thymus. Applying miR-125a-5p mimics was able to inhibit FoxN1 3′UTR luciferase activity in a 293T cell line and to suppress FoxN1 expression in murine TEC Z210 cells. Since a single miRNA can play a fine-tuning role to regulate expression of multiple genes and a single gene can be regulated by multiple miRNAs, our result adds a single miRNA, miR-125a-5p, into the panel of FoxN1-regulating miRNAs associated with thymic aging.

During the entire processes of thymus organogenesis, maturation, and involution, gene regulation occurs post-transcriptionally via recently discovered microRNA (miRNA) transcripts. Numerous reports indicate that miRNAs may be involved in the construction of a normal thymic microenvironment, which constitutes a critical component to support T lymphocyte development. MiRNAs are also expressed in thymic stromal cells including thymic epithelial cells (TECs) during maturation and senescence. This review focuses on the function of miRNAs in thymic development and involution. A better understanding of these processes will provide new insights into the regulatory network of TECs and further comprehension of how genes control TECs to maintain the thymic microenvironment during thymus development and aging, thus supporting a normal cellular immune system.

Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent, and the challenge of prevention and treatment is increasing. The “multiple hits” hypothesis of multiple insults, such as dietary fat intake, de novo lipogenesis, insulin resistance, oxidative stress, mitochondrial dysfunction, gut dysbiosis and hepatic inflammation, can provide a more accurate explanation of the pathogenesis of NAFLD. Betaine plays important roles in regulating the genes associated with NAFLD through anti-inflammatory effects, increased free fatty oxidation, anti-lipogenic effects, and improved insulin resistance and mitochondrial function; however, the mechanism of betaine remains elusive.