In the frame of radiotherapy treatment of cancer, radioresistance remains a major issue that still needs solutions to be overcome. To effectively improve the radiosensitivity of tumors and reduce the damage of radiation to neighboring normal tissues, radiosensitizers have been given increasing attention in recent years. As nanoparticles based on the metal element gadolinium, AGuIX nanoparticles have been shown to increase the radiosensitivity of cancers. Although it is a rare nanomaterial that has entered preclinical trials, the unclear biological mechanism hinders its further clinical application. In this study, we demonstrated the effectiveness of AGuIX nanoparticles in the radiosensitization of triple-negative breast cancer. We found that AGuIX nanoparticles increased the level of DNA damage by compromising the homologous recombination repair pathway instead of the non-homologous end joining pathway. Moreover, the results showed that AGuIX nanoparticles induced apoptosis, but the degree of apoptosis ability was very low, which cannot fully explain their strong radiosensitizing effect. Ferroptosis, the other mode of cell death, was also discovered to play a significant role in radiation sensitization, and AGuIX nanoparticles may regulate the anti-ferroptosis system by inhibiting the NRF2-GSH-GPX4 signaling pathway.
Leukemia stem cells in acute myeloid leukemia (AML) can persist within unique bone marrow niches similar to those of healthy hematopoietic stem cells and resist chemotherapy. In the context of AML, endothelial cells (ECs) are crucial components of these niches that appear to promote malignant expansion despite treatment. To better understand these interactions, we developed a real-time cell cycle-tracking mouse model of AML (Fucci-MA9) with an aim of unraveling why quiescent leukemia cells are more resistant to chemotherapy than cycling cells and proliferate during disease relapse. We found that quiescent leukemia cells were more prone to escape chemotherapy than cycling cells, leading to relapse and proliferation. Importantly, post-chemotherapy resting leukemia cells tended to localize closer to blood vessels. Mechanistically, after chemotherapy, resting leukemia cells interacted with ECs, promoting their adhesion and anti-apoptotic capacity. Further, expression analysis of ECs and leukemia cells during AML, after chemotherapy, and after relapse revealed the potential of suppressing the post-chemotherapy inflammatory response to regulate the functions of leukemia cells and ECs. These findings highlight the role of leukemia cells in evading chemotherapy by seeking refuge near blood vessels and provide important insights and directions for future AML research and treatment.
Nuclear pollution is one of the main environment pollution. And Almost all of the waste of the nuclear accident will cause human skin radiation damage because of the special physiological location and the characterics of the skin cells. Different from other skin injuries, cutaneous radiation injury (CRI) is caused by the loss of a large number of stem cells which is very sensitive to radiation. Gingiva mesenchymal stem cells (GMSCs) have the characteristics of self-renewal, pluripotent differentiation, and immune regulatory cells both in vitro and in vivo and are easy to obtain without carcinogenicity than other stem cells. To prolong the residence time of the stem cells at the site of injury, Nap-GDFDFpDY (pY-Gel) self-assembling peptide hydrogels have been used in this study. Results revealed GMSCs can obviously alleviate skin injury induced from high-dose IR in mice and promote skin healing. And in cellular experiments, GMSCs conditioned medium (CM) can promote the proliferation and migration of skin cells, enhance the ability of DNA damage repair and reduce the inflammatory response. In addition, The findings of this study suggest that the mechanism may involve the activation of the EGFR/STAT3 signaling pathway in skin cells to promote the repair of skin cells after exposure to radiation.
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