Vascular endothelial damage due to ionizing radiation is the main pathological process of radiation injury and the main cause of damage to various organs in nuclear accidents. Ferroptosis plays an important role in ionizing radiation-induced cell death. We have previously reported that luteolin is highly resistant to ferroptosis. In the present study, body weight, microvessel count, H&E, and Masson staining results showed that luteolin rescued radial vascular injury in vivo. Cell Counting Kit 8 (CCK8), Giemsa staining clarified the anti-ferroptosis ability of luteolin with low toxicity. Malondialdehyde (MDA), superoxide dismutase (SOD), NADP⁺/NADPH, Fe²⁺ staining, dihydroethidium (DHE) and MitoTracker assays for ferroptosis-related metrics, we found that luteolin enhances human umbilical vein endothelial cells (HUVECs) antioxidant damage capacity. Drug affinity responsive target stability (DARTS), surface plasmon resonance (SPR), computer simulated docking and western blot showed that heat shock protein beta-1 (HSPB1) is one of the targets of luteolin action. Luteolin inhibits ferroptosis by promoting the protein expression of HSPB1/solute carrier family 7 member 11 (SLC7A11)/ glutathione peroxidase 4 (GPX4). In conclusion, we have preliminarily elucidated the antioxidant damage ferroptosis ability and the target of action of luteolin to provide a theoretical basis for the application of luteolin in radiation injury diseases.

Mesenchymal stem cells (MSCs) exhibit therapeutic potential for ulcerative colitis (UC) due to their immunomodulatory, homing, and tissue repair capabilities, but clinical efficacy is constrained by heterogeneity. Induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) exhibit superior stem cell properties compared to traditional MSCs, with CD146+ MSCs exhibiting enhanced biological characteristics. Nevertheless, the biological properties of CD146+iMSCs, as well as their therapeutic potential in UC, remain unclear. CD146+ subpopulations were isolated from iMSCs and umbilical cord-derived MSCs (UCMSCs) using magnetic beads sorting. The surface markers, proliferation capacity, differentiation potential, and regulatory effects on macrophage polarization were analyzed. Dextran sulfate sodium (DSS) - induced UC mouse models were established and treated with CD146+iMSCs. Body weight, disease activity index (DAI), colon length, and histopathological damage were evaluated. Peripheral immune cells and cytokines were analyzed by flow cytometry and ELISA. Transcriptome sequencing of colon tissues was performed and jointly analyzed with GEO datasets to identify the mechanisms of CD146+iMSCs’ therapeutic efficacy in UC through differential gene expression profiling, protein-protein interaction network, functional enrichment analysis, and immune infiltration assessment. The core mechanisms were validated in vitro and vivo. CD146+ iMSCs exhibited similar morphology and macrophage polarization regulatory capacity to CD146+UCMSCs, with superior proliferation and differentiation potential. CD146+ iMSCs significantly ameliorated UC symptoms (weight, DAI), reduced colon damage, decreased IL-6/TNF-α, and restored immune balance. Integrated analysis of colon transcriptome sequencing data and GEO datasets revealed the pivotal role of the IL-17 signaling pathway in the therapeutic effects of CD146+iMSCs. CD146+iMSCs effectively suppressed IL-17 expression both in cell inflammation models and colon tissues, downregulated nine hub genes, and inhibited macrophage polarization via the cGAS-STING axis. CD146+iMSCs exhibited advantages in proliferative and differentiation capabilities. They could ameliorate UC by suppressing IL-17 expression, downregulating HUB genes, and modulating macrophage polarization through the cGAS-STING axis.

Background: Combined radiation and wound injury is a refractory complication in radiotherapy, closely associated with persistent radiation-induced oxidative stress and apoptosis. Mesenchymal stromal cell (MSC) therapy shows promise but is limited by poor cell survival in the irradiated microenvironment. This study investigated the therapeutic effects and mechanisms of local injection of human umbilical cord mesenchymal stromal cells genetically modified to overexpress manganese superoxide dismutase (MnSOD-hUCMSCs) on combined radiation and wound injury. Methods: MnSOD-hUCMSCs were established using an adenoviral vector, and their conditioned medium (MnSOD-CM) was collected. A mouse model of combined radiation and wound injury was used to evaluate the wound-healing effects of local MnSOD-hUCMSCs injection. In vitro , MnSOD-CM was applied to irradiated HaCaT and HFF-1 cells. Cell viability, migration, oxidative stress, mitochondrial function, and apoptosis were assessed. Results: MnSOD-hUCMSCs with improved antioxidant capacity were generated, and their conditioned medium (MnSOD-CM) recapitulated the cytoprotective effects of MnSOD-hUCMSCs in vitro . Local injection of MnSOD-hUCMSCs significantly promoted wound healing, accelerated re-epithelialization, increased collagen deposition, and reduced apoptosis in vivo . Mechanistically, MnSOD-hUCMSCs exerted effects through paracrine-mediated delivery via their conditioned medium, regulating the Bax/Bcl-2 balance and inhibiting PARP cleavage to block apoptosis. Conclusion: Local injection of MnSOD-hUCMSCs effectively treats combined radiation and wound injury via their paracrine factors present in the conditioned medium. These findings suggest that paracrine factors secreted by MnSOD-hUCMSCs play a critical role in alleviating radiation-induced skin injury. The relative contribution of paracrine factors and other potential mechanisms warrants further investigation. This study offers a novel therapeutic strategy for radiation-induced skin injury.

Renal fibrosis, the common endpoint of chronic kidney disease, is exacerbated by renal ischemia. While human iPSC-derived MSCs (iMSCs) hold therapeutic pro