Selenium (Se) is an essential trace element known for its significant role in maintaining human health and mitigating disease progression. Selenium and its compounds exhibit high selective cytotoxicity against tumor cells. However, their anti-cervical cancer (CC) effects and underlying mechanisms have not been fully explored. This study found that sodium selenite (SS) inhibits the viability of HeLa and SiHa cells in a dose- and time-dependent manner. Intraperitoneal injection of 3 and 6 mg/kg SS for 14 days in female nude mice significantly inhibited the growth of HeLa cell xenografts without evident hepatotoxicity or nephrotoxicity. RNA sequencing results indicated that the AMP-activated protein kinase (AMPK), Forkhead box protein O (FOXO), and apoptosis signaling pathways are key regulatory pathways in SS’s anti-CC effects, and SS’s inhibition of HeLa cell proliferation may be related to autophagy and ROS-induced apoptosis. Further research has revealed that SS induces cell autophagy and apoptosis through the AMPK/mTOR/FOXO3a pathway, characterized by the upregulation of p-AMPK/AMPK, FOXO3a, LC3-II, cleaved-caspase3, and cleaved-PARP and the downregulation of p-mTOR/mTOR and p62. Additionally, SS impaired mitochondrial function, including decreased mitochondrial membrane potential, mitochondrial Ca²⁺ overload, and accumulation of mitochondrial reactive oxygen species (mtROS). Pretreatment with Mitoquinone mesylate (Mito Q) and compound C partially reversed SS-induced apoptosis, autophagy, and proliferation inhibition. Pretreatment with 3-methyladenine (3-MA) enhances SS-induced apoptosis and proliferation inhibition in HeLa cells but reverses these effects in SiHa cells. In summary, SS induces apoptosis, autophagy, and proliferation inhibition in HeLa and SiHa cells through the activation of the AMPK/mTOR/FOXO3a signaling pathway via mtROS. Autophagy activation may be a major risk factor for SS-induced apoptosis in SiHa cells but can protect HeLa cells from SS-induced apoptosis. These findings provide new evidence for understanding the molecular mechanisms underlying SS in potential new drug development for CC.

Fluoride exposure has been shown to affect immune cell subsets and immune function, but its impact on macrophage polarization remains unclear. This study investigates the effects of low fluoride exposure on macrophage polarization and its underlying mechanisms through epidemiological surveys, animal experiments, and in vitro cell experiments. In the population-based epidemiological survey, we used mass cytometry to assess the impact of low fluoride exposure (0.570–2.027 mg/L) in the environment on human immune cell populations following the current water improvement and fluoride reduction measures. A rat fluorosis model was established by treating rats with sodium fluoride (NaF) in drinking water at concentrations of 0 mg/L, 5 mg/L, 10 mg/L, 25 mg/L, and 50 mg/L for 90 days., and morphological changes were assessed by hematoxylin–eosin (H&E) staining and transmission electron microscopy in the spleen of rats. Flow cytometry was used to analyze the proportion of macrophage subtypes in the spleen, while Western blot and immunofluorescence were performed to detect the expression of mitochondrial autophagy-related proteins. An M1 macrophage model was constructed in vitro by inducing THP-1 cells, and the effects of fluoride on macrophage-related cell markers and cytokines were assessed using flow cytometry and ELISA, respectively, following intervention with an autophagy inhibitor. Mitochondrial membrane potential and mitochondrial–lysosomal colocalization are analyzed through flow cytometry and confocal microscopy. The study aims to investigate the role of mitophagy in sodium fluoride-induced macrophage polarization. Epidemiological investigations revealed that low fluoride increases the proportion of blood monocytes, as well as the expression levels of CD68 (a macrophage surface marker), CD86 (an M1 macrophage marker), and the inflammatory cytokine IFN-γ in peripheral blood mononuclear cells (PBMCs). In the rats of NaF-treated groups, splenic tissues exhibited inflammatory infiltration, mitochondrial swelling, and increased autophagosome formation. Moreover, low fluoride activated the PINK1/Parkin-mediated mitophagy pathway, promoting an increase in the M2/M1 macrophage ratio. In vitro experiments further confirmed that autophagy inhibitors reversed the NaF-induced increase in the M2/M1 macrophage ratio. This study demonstrates that low fluoride induces inflammatory responses in the body and drives M1 macrophage polarization toward M2 macrophages via mitophagy. These findings highlight the potential immunological risks associated with low fluoride and provide mechanistic insights into the interplay among fluoride, mitophagy, and macrophage polarization.

Background: Selenium (Se) is an essential trace element for maintaining human health, with significant antioxidant and immunoregulatory functions. Inadequate Se intake may be associated with Keshan disease, Kashin–Beck disease, and hypothyroidism. However, effective indicators for scientifically guiding Se supplementation in Se-deficient populations are still lacking. Objectives: This study aims to explore the dynamic distribution of Se across various nutritional biomarkers and major organs in rats through a Se supplementation experiment, as well as the pairwise correlations between them, in order to identify reliable nutritional indicators for evaluating Se levels in the body. Methods: Se levels in hair, blood, and major tissues and organs were determined by atomic fluorescence spectrometry, and glutathione peroxidase (GSH-Px) levels were measured using an ELISA. Results: Se supplementation significantly increased Se levels in rat blood, hair, and major organs, as well as GSH-Px levels in blood. Se primarily accumulated in the liver and kidneys, followed by myocardium, spleen, and muscles. Serum and plasma Se were found to be the best indicators of short-term Se intake, while erythrocyte Se levels showed a stronger correlation with Se levels in tissues and organs, making it a better marker for assessing long-term Se nutritional status compared to hair Se. Conclusions: This study demonstrates the potential of erythrocyte Se levels as an indicator for evaluating long-term Se nutritional status, providing scientific evidence for Se nutritional assessments.