Tristetraprolin (TTP), an important immunosuppressive protein regulating mRNA decay through recognition of the AU-rich elements (AREs) within the 3′-UTRs of mRNAs, participates in the pathogenesis of liver diseases. However, whether TTP regulates mRNA stability through other mechanisms remains poorly understood. Here, we report that TTP was upregulated in acute liver failure (ALF), resulting in decreased mRNA stabilities of CCL2 and CCL5 through promotion of N ⁶ -methyladenosine (m ⁶ A) mRNA methylation. Overexpression of TTP could markedly ameliorate hepatic injury in vivo. TTP regulated the mRNA stabilization of CCL2 and CCL5. Interestingly, increased m ⁶ A methylation in CCL2 and CCL5 mRNAs promoted TTP-mediated RNA destabilization. Moreover, induction of TTP upregulated expression levels of WT1 associated protein, methyltransferase like 14, and YT521-B homology N ⁶ -methyladenosine RNA binding protein 2, which encode enzymes regulating m ⁶ A methylation, resulting in a global increase of m ⁶ A methylation and amelioration of liver injury due to enhanced degradation of CCL2 and CCL5. These findings suggest a potentially novel mechanism by which TTP modulates mRNA stabilities of CCL2 and CCL5 through m ⁶ A RNA methylation, which is involved in the pathogenesis of ALF.

Oxidative stress and chronic inflammation are major contributors to skin aging, promoting collagen degradation and impairing dermal structure. These factors stimulate the expression of matrix metalloproteinases, accelerating collagen breakdown and leading to wrinkles, sagging, and loss of elasticity. Given the key role of collagen in maintaining skin firmness and integrity, strategies that enhance collagen synthesis are essential for anti-aging interventions. This study investigated the combined effects of Yeast/Rice Fermentation Filtrate (RFF) and sialic acid (SA) on collagen production, antioxidation, and anti-inflammation, as well as their underlying mechanisms. The combination of RFF and SA significantly increased collagen genes transcription and mRNA stability, thereby enhancing collagen accumulation in the extracellular matrix. RNA-seq analysis revealed that RFF and SA modulate genes involved in the IL-17 signaling pathway. Mechanistically, RFF enhanced collagen mRNA stability by regulating HuR, while SA promoted collagen gene transcription via the TGF-β/Smad pathway. Moreover, the combination reduced the expression of inflammatory markers (IL-1β, IL-6, IL-8, PGE2, and NO) and improved cellular resistance to oxidative and inflammatory stress. These findings support the application of RFF and SA in anti-aging cosmetics and propose a novel strategy to enhance collagen production by simultaneously upregulating gene expression and stabilizing collagen mRNA.

Ultraviolet A (UVA) radiation induces oxidative stress and mitochondrial dysfunction in dermal fibroblasts, contributing to photodamage and skin aging. This study investigated the protective effects of Yeast/rice fermentation filtrate (RFF) and sialic acid (SA), both individually and in combination, against UVA-induced damage in human dermal fibroblasts. Cell viability, reactive oxygen species (ROS) levels, intracellular ATP and NAD⁺ contents, and mitochondrial membrane potential (ΔΨm) were evaluated following treatment. RFF, SA, and their combination significantly improved cell viability in UVA-damaged fibroblasts and reduced ROS generation. Notably, the combined treatment increased intracellular ATP levels by 201.2% (p < 0.05), with enhancements of 62.3% and 285.4% compared to RFF and SA alone, respectively. Additionally, the combined treatment significantly restored NAD⁺ levels and effectively preserved mitochondrial membrane potential. Transcriptomic analysis revealed modulation of pathways related to cellular energy metabolism, particularly AMPK, and upregulation of SIRT1, SIRT3, and SIRT5 expression. The RFF–SA combination confers robust UVA photoprotection by enhancing mitochondrial resilience, providing a foundation for the development of protective cosmetic formulations.