Quercetin has been shown to have a wide range of beneficial effects, such as anti-inflammation, anti-oxidation and immunomodulation. The study was designed to explore the role and molecular mechanisms of quercetin on the protective effect of bone marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress in vitro. BMSCs were isolated from 4-week-old male Sprague–Dawley rats. Upon H₂O₂ stimulation in vitro, the effects of quercetin on the proliferation, anti-oxidation and osteogenic differentiation of BMSCs were evaluated by Cell Counting Kit-8, reactive oxygen species analysis, Western blot (WB), real-time PCR (RT-PCR), alkaline phosphatase staining and alizarin red staining. Additionally, ferroptosis-related markers were examined by WB, RT-PCR and Mito-FerroGreen. Finally, PI3K/AKT/mTOR signaling pathway was explored in these processes. We found that quercetin significantly maintained BMSCs viability upon H₂O₂ stimulation. Quercetin upregulated protein (ALP, OPN and RUNX2) and mRNA (Alp, Opn, Ocn and Runx2) levels of osteogenic markers, downregulated ROS levels and upregulated antioxidative gene expressions (Nrf2, Cat, Sod-1 and Sod-2) compared with the H₂O₂ group. The ferroptosis in BMSCs was activated after H₂O₂ stimulation, and the phosphorylation level of PI3K, AKT and mTOR was upregulated in H₂O₂-stimulated BMSCs. More importantly, quercetin inhibited ferroptosis and the phosphorylation level of PI3K, AKT and mTOR were downregulated after quercetin treatment. We conclude that quercetin maintained the viability and the osteoblastic differentiation of BMSCs upon H₂O₂ stimulation, potentially via ferroptosis inhibition by PI3K/AKT/mTOR pathway.

The treatment of infected bone defects (IBDs) needs simultaneous elimination of infection and acceleration of bone regeneration. One mechanism that hinders the regeneration of IBDs is the iron competition between pathogens and host cells, leading to an iron deficient microenvironment that impairs the innate immune responses. In this work, an in situ modification strategy is proposed for printing iron‐active multifunctional scaffolds with iron homeostasis regulation ability for treating IBDs. As a proof‐of‐concept, ultralong hydroxyapatite (HA) nanowires are modified through in situ growth of a layer of iron gallate (FeGA) followed by incorporation in the poly(lactic‐co‐glycolic acid) (PLGA) matrix to print biomimetic PLGA based composite scaffolds containing FeGA modified HA nanowires (FeGA‐HA@PLGA). The photothermal effect of FeGA endows the scaffolds with excellent antibacterial activity. The released iron ions from the FeGA‐HA@PLGA help restore the iron homeostasis microenvironment, thereby promoting anti‐inflammatory, angiogenesis and osteogenic differentiation. The transcriptomic analysis shows that FeGA‐HA@PLGA scaffolds exert anti‐inflammatory and pro‐osteogenic differentiation by activating NF‐κB, MAPK and PI3K‐AKT signaling pathways. Animal experiments confirm the excellent bone repair performance of FeGA‐HA@PLGA scaffolds for IBDs, suggesting the promising prospect of iron homeostasis regulation therapy in future clinical applications.

Porphyromonas gingivalis (P.gingivalis) is associated with the onset of Alzheimer's disease (AD), but the underlying molecular mechanism is unclear. Neuroinflammation in the brain from the microglial immune response induces the pathological progression of AD. In this study, the roles and molecular mechanism of P.gingivalis in microglial inflammation in vitro were investigated. In this study, a P.gingivalis oral administration mouse model was generated, and microglia were stimulated with P.gingivalis in vitro. The viability of the microglia after P.gingivalis treatment was evaluated through CCK-8 and live/dead cell staining. Inflammation in brain tissue after P.gingivalis treatment and the immune response of microglia in vitro were detected by RT‒PCR, Western blotting and IF. Moreover, the RNA sequence was used, and the role of the NF-κB signalling pathway in microglial activation was analysed after P.gingivalis stimulation. The mRNA and protein levels of IL-6 and IL-17 were increased, and the expression of IL-10 was decreased in brain tissue after P.gingivalis oral administration. The viability of the HMC3 cells significantly decreased with 5% P.gingivalis after stimulation. The results of live/dead cell staining also showed the inhibitory effect of 5% P.gingivalis supplementation on cell viability. Moreover, 5% P.gingivalis supplementation increased the mRNA and protein levels of IL-6 and IL-17 and decreased IL-10 expression in HMC3 cells. P.gingivalis supplementation increased the mRNA and protein levels of iNOS and CD86 and decreased CD206 expression in HMC3 cells. RNA sequencing revealed that the NF-κB signalling pathway was involved in this process. Furthermore, p-P65 was upregulated and p-IKBα was downregulated in brain tissue and HMC3 cells after P.gingivalis stimulation, and an NF-κB signalling pathway inhibitor (QNZ) reversed the viability, M1 polarization and inflammatory factors of microglia in HMC3 cells in vitro. In conclusion, P.gingivalis induced neuroinflammation in the brain, possibly through promotion of M1 polarization of microglia via activation of the NF-κB signalling pathway during the progression of AD.

Obstructive sleep apnea (OSA) is a common respiratory disorder, primarily characterized by two pathological features: chronic intermittent hypoxia (CIH) and sleep deprivation (SD). OSA has been identified as a risk factor for numerous diseases, and the inflammatory response related to programmed cell necrosis is believed to play a significant role in the occurrence and progression of multisystem damage induced by OSA, with increasing attention being paid to pyroptosis. Recent studies have indicated that OSA can elevate oxidative stress levels in the body, activating the process of pyroptosis within different tissues, ultimately accelerating organ dysfunction. However, the molecular mechanisms of pyroptosis in the multisystem damage induced by OSA remain unclear. Therefore, this review focuses on four major systems that have received concentrated attention in existing research in order to explore the role of pyroptosis in promoting renal diseases, cardiovascular diseases, neurocognitive diseases, and skin diseases in OSA patients. Furthermore, we provide a comprehensive overview of methods for inhibiting pyroptosis at different molecular levels, with the goal of identifying viable targets and therapeutic strategies for addressing OSA-related complications.