Elesclomol Loaded Copper Oxide Nanoplatform Triggers Cuproptosis to Enhance Antitumor Immunotherapy.

The induction of cuproptosis, a recently identified form of copper-dependent immunogenic cell death, is a promising approach for antitumor therapy. However, sufficient accumulation of intracellular copper ions (Cu2+) in tumor cells is essential for inducing cuproptosis. Herein, an intelligent cuproptosis-inducing nanosystem is constructed by encapsulating copper oxide (CuO) nanoparticles with the copper ionophore elesclomol (ES). After uptake by tumor cells, ES@CuO is degraded to release Cu2+ and ES to synergistically trigger cuproptosis, thereby significantly inhibiting the tumor growth of murine B16 melanoma cells. Moreover, ES@CuO further promoted cuproptosis-mediated immune responses and reprogrammed the immunosuppressive tumor microenvironment by increasing the number of tumor-infiltrating lymphocytes and secreted inflammatory cytokines. Additionally, combining ES@CuO with programmed cell death-1 (PD-1) immunotherapy substantially increased the antitumor efficacy in murine melanoma. Overall, the findings of this study can lead to the use of a novel strategy for cuproptosis-mediated antitumor therapy, which may enhance the efficacy of immune checkpoint inhibitor therapy.

Effect of dietary pattern on pregnant women with gestational diabetes mellitus and its clinical significance.

Gestational diabetes mellitus (GDM) is a common obstetric disease among pregnant women. This study aimed to explore the effect of dietary pattern management to reduce the incidence of GDM. Here, we, retrospectively, analyzed the influence of dietary patterns on the occurrence of GDM and the correlation between dietary patterns and intestinal microbiome distribution and inflammation in pregnant women. Moreover, patients were assigned to the dietary pattern management group and the nondietary pattern management group, and the effects of dietary patterns on the intestinal microbiome distribution and inflammatory factors were investigated. We found that the intestinal microbiome was changed in GDM patients compared with the healthy controls. The relative abundance of probiotics Lactobacillus and Bifidobacterium significantly decreased in patients with GDM. Moreover, compared with the control group, the expression levels of interleukin-6 and tumor necrosis factor-α were significantly increased. Furthermore, dietary pattern management led to intestinal microbiome changes in patients with GDM. In conclusion, dietary pattern management could alleviate GDM via affecting the intestinal microbiome as well as inflammatory conditions in patients.

Effects of maternal exposure to di-n-butyl phthalate during pregnancy and breastfeeding on ovarian development and function of F1 female rats.

This study aimed to investigate the effects of maternal exposure to di-n-butyl phthalate (DBP) during pregnancy and breastfeeding on F1 ovarian development and function. A rat model of maternal exposure to DBP during pregnancy and breastfeeding was established by gavage feeding female Sprague Dawley rats with 0, 10, 100, or 600mg/kg/day DBP from gestational day (GD) 12 to postnatal day (PND) 21. F1 offspring were weaned on PND21 and were not exposed to DBP afterward. The age of vaginal opening and estrus onset, estrous cyclicity, c-Kit-ligand expression on ovarian granulosa cells, and the weight of ovaries and uterus of F1 female offspring were not affected, whereas serum levels of estradiol and progesterone were increased significantly by maternal exposure to 10mg/kg/day DBP from GD12 to PND21. Although F1 ovarian function may not be adversely affected by maternal exposure to DBP, the increased reproductive hormone levels may interfere in F1 rat fertility.