Ferroptosis of mesenchymal stem cells (MSCs) is a critical bottleneck restricting the efficiency of ruminant biological breeding. Phloretin, a natural bioactive polyphenol, exhibits potential ferroptosis-inhibitory activity. However, the regulatory effects and underlying mechanisms of phloretin on ruminant MSCs remain poorly understood. This study aimed to investigate the effects of phloretin on ferroptosis and elucidate its underlying molecular mechanisms. Herein, we isolated and cultured adipose-derived mesenchymal stem cells (AD-MSCs) from adipose tissue of a 9-day-old Leizhou goat and established a ferroptosis model in these cells using RSL3. We detected cell viability, proliferation, migration, ferroptosis-related indexes and key protein expression. The results showed that phloretin (25 and 50 μM) dose-dependently inhibited ferroptosis in goat AD-MSCs, reducing intracellular ferrous ion (Fe²⁺), reactive oxygen species (ROS) and lipid peroxidation levels, restoring glutathione content, and ameliorating mitochondrial structural damage. Mechanistically, phloretin exerted its anti-ferroptosis effects through direct antioxidant activity, activation of the Nrf2/HO-1/GPX4 signaling pathway and Fe²⁺ chelation. Nrf2 and GPX4 were key targets in this process. These results provide preliminary in vitro evidence and a theoretical basis for the potential application of phloretin in future research related to meat goat production and ruminant breeding.

Treatment for acute liver failure (ALF) is constrained by shortages of liver transplant donors and immune rejection. Porcine bone marrow mesenchymal stem cells (pBMSCs) demonstrate clinical potential in xenotransplantation due to their abundant availability, low immunogenicity, and strong proliferative activity. This study is the first to investigate the reparative effects and mechanisms of pBMSCs derived from Luopan Mountain pigs in a D-galactosamine (D-GalN)-induced ALF rat model. The results demonstrated that tail-vein transplantation of pBMSCs significantly improved survival rates in ALF rats; reduced serum ALT, AST, and TBIL levels; enhanced hepatic glycogen metabolism; and mitigated histopathological liver damage. Additionally, pBMSC transplantation upregulated serum HGF, IGF-1, and VEGF levels while inhibiting hepatocyte apoptosis. Mechanistic studies indicate that pBMSCs promote liver function recovery and regeneration by activating the PI3K/Akt/mTOR signaling pathway and suppressing its key negative regulator, PTEN, by regulating the expression of key genes involved in inflammation, fibrosis, proliferation, and apoptosis. This study provides crucial experimental evidence for the use of pBMSCs in treating acute liver failure (ALF) and lays the groundwork for its clinical translation in the field of xenotransplantation.

Acute liver injury (ALI) involves complex pathogenesis and lacks effective clinical therapies. Although mesenchymal stem cells (MSCs) demonstrate therapeutic potential, the role and mechanisms of adipose-derived mesenchymal stem cells (ADSCs) from Luopan Mountain pigs remain unclear. This study assessed the therapeutic potential of Luopan Mountain pig ADSCs in a D-GalN-induced rat model of ALI and investigated its association with the TLR4/MyD88/NF-κB axis. Results showed that ADSCs transplantation significantly improved liver function (by reducing ALT, AST, and TBIL levels and increasing ALB levels) and alleviated histopathological damage in liver tissue. Mechanistically, ADSCs conferred multi-faceted hepatoprotection via inhibition of the TLR4/MyD88/NF-κB axis, synergistically downregulating proinflammatory factors (TNF-α, IL-1β, IL-6, IL-8), enhancing antioxidant enzyme activity (SOD, GSH-PX), and promoting the expression of the hepatocyte regeneration marker Ki67. We demonstrate for the first time that Luopan Mountain pig ADSCs synergistically repair acute liver injury by inhibiting the TLR4/MyD88/NF-κB pathway, offering novel insights for cell therapy in ALI.