Radiotherapy has been used for decades in the treatment of liver cancer. We previously found that adiponectin receptor (AdipoR1) is a prognostic biomarker for hepatoma carcinoma (HCC) after stereotactic body radiation therapy (SBRT) and blocking AdipoR1 enhances radiation sensitivity in hepatoma carcinoma cells. In the current study, we aimed to elucidate the roles of AdipoR1 in ionizing radiation- (IR-) induced radiosensitivity by activating ferroptosis pathway in HCC cells. We found that IR upregulated the expression of AdipoR1 and furthermore promoted the protein stability of transcription factor Nrf2, Nrf2 binded to the xCT promoter and increased xCT transcription and expression, and this directly contributed to the protective function in the early stage of radiation in HCC cells. AdipoR1 knockdown significantly inhibited expression of Nrf2 and xCT and, furthermore, increased both IR- and erastin-induced ferroptosis, which could be abolished by the rescue of Nrf2 and xCT. For the first time, we found that radiation-induced ferroptosis was mediated by AdipoR1-Nrf2-xCT pathway in HCC cells. These results provide new insights to the development and application of novel therapeutic strategies for hepatoma carcinoma.

Background We analyzed whether a maternity waiting home (MWH) for pregnant women in an obstetrically underserved area of Gangwon-do in Korea, which has been in operation since August 2018, has improved the accessibility of a maternity hospital and pregnancy outcomes. Methods We compared and analyzed the accessibility of maternity hospitals for 170 pregnant women who applied for the MWH from August 2018 to May 2022. Among the 170 participants, 64 were MWH users and 106 non-users. The effect on pregnancy outcomes between MWH users and non-users was analyzed in the 160 people who achieved a pregnancy outcome. Results Although the average distance and travel time from the pregnant women’s residence in the obstetrically underserved area to a maternity hospital were 56.4 ± 1.6 km and 63.4 ± 1.4 minutes, respectively, the average distance between the MWH and the MWH users’ maternity hospital was 2.7 ± 0.2 km, and the travel time was 10.7 ± 0.6 minutes. The distance was 55.6 km closer on average and the travel time 54.1 minutes shorter. MWH users gave birth at a significantly later gestation age (38.9 ± 0.2 vs. 38.3 ± 0.15 weeks, P = 0.024) and to infants with heavier birth weights (3,300 ± 60 vs. 3,100 ± 50 gm, P = 0.024) compared with non-users. The rate of Cesarean section was significantly higher in the MWH users (47.5% vs. 44.6%, P = 0.047). The MWH users tended to be associated with a lower rate of neonatal intensive care unit admission (5.1% vs. 11.0%, P = 0.204), lower birth weight (< 2.5 kg) (1.7% vs. 8.0%, P = 0.155), and lower fetal death rate in the uterus (0% vs. 1.0%, P = 1.0) compared with non-users, but the differences were not significant. Conclusion The MWH helped pregnant women in obstetrically underserved areas by improving accessibility to a maternity hospital and lengthening gestation. As a result, neonatal birth weight was heavier for MWH users than non-users. MWHs in Korea can provide an alternative way to improve accessibility to maternity healthcare for pregnant women in obstetrically underserved areas, where it is difficult to establish maternity hospitals, and thereby will improve their pregnancy outcomes.