Selenium Biofortification Enhanced miR167a Expression in Broccoli Extracellular Vesicles Inducing Apoptosis in Human Pancreatic Cancer Cells by Targeting IRS1.

Purpose: Pancreatic adenocarcinoma (PAAD) presents an extremely high morbidity and mortality rate. Broccoli has excellent anti-cancer properties. However, the dosage and serious side effects still limit the application of broccoli and its derivatives for cancer therapy. Recently, extracellular vesicles (EVs) derived from plants are emerging as novel therapeutic agents. Thus, we conducted this study to determine the effectiveness of EVs isolated from Se-riched broccoli (Se-BDEVs) and conventional broccoli (cBDEVs) for the treatment of PAAD. Methods: In this study, we first isolated Se-BDEVs and cBDEVs by a differential centrifugation method, and characterized them by using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Then, miRNA-seq was combined with target genes prediction, and functional enrichment analysis to reveal the potential function of Se-BDEVs and cBDEVs. Finally, the functional verification was conducted in PANC-1 cells. Results: Se-BDEVs and cBDEVs exhibited similar characteristics in size and morphology. Subsequent miRNA-seq revealed the expression of miRNAs in Se-BDEVs and cBDEVs. Using a combination of miRNA target prediction and KEGG functional analysis, we found miRNAs in Se-BDEVs and cBDEVs may play an important role in treating pancreatic cancer. Indeed, our in vitro study showed that Se-BDEVs had greater anti-PAAD potency than cBDEVs due to increased bna-miR167a_R-2 (miR167a) expression. Transfection with miR167a mimics significantly induced apoptosis of PANC-1 cells. Mechanistically, further bioinformatics analysis showed that IRS1, which is involved in the PI3K-AKT pathway, is the key target gene of miR167a. Conclusion: This study highlights the role of miR167a transported by Se-BDEVs which could be a new tool for counteracting tumorigenesis.

Effects of selenium supplementation on concurrent chemoradiotherapy in patients with cervical cancer: A randomized, double-blind, placebo-parallel controlled phase II clinical trial.

Objective: Selenium (Se) is an essential trace element and may affect cervical cancer occurrence and progression. The association between selenium supplementation and acute toxic reactions and clinical outcomes in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy remains unclear. The aim of this study was to determine the safety profile of add-on Se yeast and assess the potential of Se to ameliorate the hematologic toxicity of concurrent chemoradiotherapy in patients with cervical cancer. Methods: Patients with Federation International of Gynecology and Obstetrics (FIGO) stage IIB cervical cancer who met all inclusion criteria were randomly assigned to either the experimental group or the control group. The experimental group received Se yeast tablets (100 µg Se, twice daily), while the control group received placebos (twice daily) for 5 weeks in total. All patients in both groups received standard treatment, including pelvic external irradiation, concurrent five cycles of chemotherapy, and brachytherapy. Measures included the incidence of myelosuppression, impairment of liver and kidney function, objective response rate (ORR), and blood Se concentrations before, during and after the treatment of the two groups. Results: A total of 104 eligible patients were enrolled in the experimental group (n = 50) or the control group (n = 54). The ORR in the experimental group and control group were 96 and 94%, respectively (p = 0.47). The baseline levels of blood Se before treatment in the experimental and control groups were similar (58.34 ± 17.63 µg/L and 60.21 ± 18.42 µg/L, p = 0.60), but the concentrations became significantly different after course completion between the two groups (76.16 ± 24.47 µg/L and 57.48 ± 14.92 µg/L, respectively, p < 0.01). Se dramatically decreased the incidence of grade 3 myelosuppression (48% vs. 63%, p = 0.034) compared to the control group. In the subgroup of patients with moderately well-differentiated cervical cancer, the incidence of thrombocytopenia induced by concurrent chemoradiotherapy was lower in the experimental group than in the control group (53.8% vs. 78.9%, p < 0.01). However, no difference was observed in liver and kidney injuries between the two groups. Conclusion: Supplementation with Se effectively increased blood Se levels in Se-inadequate cervical cancer patients. As an add-on to standard treatment, Se-yeast significantly decreased the hematologic toxicity of concurrent chemoradiotherapy.

Dietary selenomethionine attenuates obesity by enhancing beiging process in white adipose tissue.

Imbalanced nutrient intake causes abnormal energy metabolism, which results in obesity. There is feasible evidence that selenium-rich (Se-rich) foods may alleviate obesity and enhance general public health, but the underlying mechanisms remain elusive. Herein we examined the effect of Se supplementation on white adipose tissue beiging process. The mice were fed with a normal diet or a Se-deficient high-fat diet (DHFD) until significant differences in terms of body weight, glucose tolerance and insulin sensitivity. Next, mice in the DHFD group were changed to a high-fat diet (HFD) containing specified amounts of selenomethionine (SeMet) (0, 150, 300, and 600 µg/kg) and continued to feed for 14 weeks. Notably, 150 µg/kg SeMet supplement highly protected mice from DHFD-induced obesity, insulin resistance, and lipid deposits in the liver and kidney, and featured by the enhanced beiging process in white adipose tissue and increased energy expenditure. Moreover, upon cold challenge, 150 µg/kg SeMet supplement enhanced cold tolerance in mice by inducing adipose beiging to promote energy expenditure, as evidenced by the increased expression of uncoupling protein-1 (UCP1) in adipocytes. Similarly, SeMet (10 µM) promoted the differentiation of beige adipocytes from the stromal vascular fraction. Collectively, our data support that optimal supplementation of SeMet could enhance the beiging process to attenuate HFD-induced obesity, which provides new insights into the relationship between dietary SeMet and type 2 diabetes.

The Cardamine enshiensis genome reveals whole genome duplication and insight into selenium hyperaccumulation and tolerance.

Cardamine enshiensis is a well-known selenium (Se)-hyperaccumulating plant. Se is an essential trace element associated with many health benefits. Despite its critical importance, genomic information of this species is limited. Here, we report a chromosome-level genome assembly of C. enshiensis, which consists of 443.4 Mb in 16 chromosomes with a scaffold N50 of 24 Mb. To elucidate the mechanism of Se tolerance and hyperaccumulation in C. enshiensis, we generated and analyzed a dataset encompassing genomes, transcriptomes, and metabolomes. The results reveal that flavonoid, glutathione, and lignin biosynthetic pathways may play important roles in protecting C. enshiensis from stress induced by Se. Hi-C analysis of chromatin interaction patterns showed that the chromatin of C. enshiensis is partitioned into A and B compartments, and strong interactions between the two telomeres of each chromosome were correlated with histone modifications, epigenetic markers, DNA methylation, and RNA abundance. Se supplementation could affect the 3D chromatin architecture of C. enshiensis at the compartment level. Genes with compartment changes after Se treatment were involved in selenocompound metabolism, and genes in regions with topologically associated domain insulation participated in cellular responses to Se, Se binding, and flavonoid biosynthesis. This multiomics research provides molecular insight into the mechanism underlying Se tolerance and hyperaccumulation in C. enshiensis.