Melatonin Maintains Homeostasis and Potentiates the Anti-inflammatory Response in Staphylococcus aureus-Induced Mastitis through microRNA-16b/YAP1

Staphylococcus aureus is a highly infectious pathogen and is a considerable threat to food hygiene and safety. Although melatonin is thought to exert an ameliorative effect on bovine mastitis, the regulatory mechanisms are unclear. In this study, we first verified the therapeutic effect of melatonin against S. aureus in vitro and in vivo, a screening of differentially expressed miRNAs and mRNAs among the blank, and S. aureus and melatonin + S. aureus groups by high-throughput sequencing identified miR-16b and YAP1, which exhibited 1.95-fold upregulated and 1.05-fold downregulated expression, respectively. Moreover, epigenetic studies showed that S. aureus inhibited miR-16b expression by methylation (increased DNMT1 expression). Additionally, the DNMT1 expression level was significantly decreased by melatonin treatment, which might indicate that the inhibition of DNMT1 by melatonin reduces the effect of S. aureus on miR-16b. The flow cytometry, scanning and transmission electron microscopy, EdU assay, and cell morphology results indicated that miR-16b in bovine mammary epithelial cells (in vitro) and in mice (in vivo) can modulate the maintenance of homeostasis and potentiate the anti-inflammatory response. In addition, YAP1 was demonstrated to be the target gene of miR-16b through quantitative real-time polymerase chain reaction, western blot, RNA immunoprecipitation, and functional assays. This study indicates that melatonin inhibits S. aureus-induced inflammation via microRNA-16b/YAP1-mediated regulation, and these findings might provide a new strategy for the prevention of bovine mastitis, facilitating further studies good of zoonotic diseases caused by S. aureus infection

Melatonin Maintains Homeostasis and Potentiates the Anti-inflammatory Response in Staphylococcus aureus-Induced Mastitis through microRNA-16b/YAP1

Staphylococcus aureus is a highly infectious pathogen and is a considerable threat to food hygiene and safety. Although melatonin is thought to exert an ameliorative effect on bovine mastitis, the regulatory mechanisms are unclear. In this study, we first verified the therapeutic effect of melatonin against S. aureus in vitro and in vivo, a screening of differentially expressed miRNAs and mRNAs among the blank, and S. aureus and melatonin + S. aureus groups by high-throughput sequencing identified miR-16b and YAP1, which exhibited 1.95-fold upregulated and 1.05-fold downregulated expression, respectively. Moreover, epigenetic studies showed that S. aureus inhibited miR-16b expression by methylation (increased DNMT1 expression). Additionally, the DNMT1 expression level was significantly decreased by melatonin treatment, which might indicate that the inhibition of DNMT1 by melatonin reduces the effect of S. aureus on miR-16b. The flow cytometry, scanning and transmission electron microscopy, EdU assay, and cell morphology results indicated that miR-16b in bovine mammary epithelial cells (in vitro) and in mice (in vivo) can modulate the maintenance of homeostasis and potentiate the anti-inflammatory response. In addition, YAP1 was demonstrated to be the target gene of miR-16b through quantitative real-time polymerase chain reaction, western blot, RNA immunoprecipitation, and functional assays. This study indicates that melatonin inhibits S. aureus-induced inflammation via microRNA-16b/YAP1-mediated regulation, and these findings might provide a new strategy for the prevention of bovine mastitis, facilitating further studies good of zoonotic diseases caused by S. aureus infection

Accelerated Bone Regeneration by an Astaxanthin-Modified Antioxidant Aerogel through Relieving Oxidative Stress via the NRF2 Signaling Pathway

Bone regeneration of critical-sized bone defects (CSBDs) with biomimetic collagen-based aerogels remains a significant challenge due to the oxidative stress on the microenvironment. The excessive oxidative stress could induce apoptosis and dysfunction of host-derived cells. Astaxanthin (ATX) exhibits excellent antioxidant ability to block free radical chain reactions. In the present study, hybrid antioxidant collagen-derived aerogels (ATX–Col aerogels) were fabricated by a simple one-step method through the covalent cross-linking of Col and ATX. The resulting ATX–Col aerogels show porous and interconnected structures due to freeze-drying strategies. The ATX–Col aerogels exhibited excellent biocompatibility and biosafety. Furthermore, ATX–Col aerogels demonstrated favorable antioxidant capacity by eliminating intracellular ROS by activating the NRF2 signaling pathway. Finally, excellent reparative effects in repairing rat cranial defects were observed in ATX–Col aerogels. Taken together, ATX–Col aerogels can accelerate bone regeneration by relieving oxidative stress via the NRF2 signaling pathway and act as a potential bone graft for CSBD. This study provides a simple method of developing antioxidant aerogels for bone regeneration