This study investigated whether exosomal microRNA-7 (miR-7) mediates lung bystander autophagy after focal brain irradiation in mice. After 10 Gy or sham irradiation of mice brains, lung tissues were extracted for the detection of autophagy markers by immunohistochemistry, western blotting, and quantitative real-time reverse transcription PCR (qRT-PCR), meanwhile the brains were dissociated, the neuron/astrocyte/microglia/oligodendrocyte were isolated, and the miR-7 expression in each population were detected, respectively. A dual-luciferase reporter assay was developed to identify whether Bcl-2 is a target gene of miR-7. After 10 Gy or sham irradiation of astrocytes, exosomes were extracted, stained with Dil (1,1'-Dioctadecyl-3,3,3',3'-Tetramethylindocarbocyanine Perchlorate), and added into non-irradiated astrocytes. Meanwhile, Dil-stained exosomes released from 10 Gy or sham irradiated astrocytes were injected into LC3B-GFP mice via the tail vein. Lung tissues were then extracted for western blotting and qRT-PCR. Irradiation of mouse brains increased the LC3B-II/I ratio, Beclin-1 and miR-7 levels, while decreased the Bcl-2 level in non-irradiated lung tissue. Interestingly, brain irradiation remarkably increased the miR-7 expression in astrocyte and oligodendrocyte. MiR-7 significantly inhibited the luciferase activity of the wild-type Bcl-2-3′-untranslated regions (UTR) reporter vector, but not that of the Bcl-2-3′-UTR mutant vector, indicating that Bcl-2 is directly targeted by miR-7. In in vitro study, the addition of irradiated astrocyte-secreted exosomes increased the LC3B-II/I ratio, Beclin-1 and miR-7 levels, while decreased the Bcl-2 level in non-irradiated astrocytes. Further, the injection of irradiated astrocyte-secreted exosomes through the tail vein increased the lung LC3B-II/I ratio, Beclin-1 and miR-7 level, but decreased the Bcl-2 level in vivo. We concluded that exosomal miR-7 targets Bcl-2 to mediate distant bystander autophagy in the lungs after brain irradiation.

This study aimed to investigate the radiosensitizing effect of polydatin (PD) on colorectal cancer (CRC) and its underlying mechanism. The C57BL/6 mouse model of CRC was induced by treatment with azoxymethane (AOM)/dextran sodium sulfate (DSS) and then divided into four groups: control, PD alone, IR alone, and combination of PD and IR. Radiation therapy (200 cGy/min, 10Gy) was performed in mice in the experimental groups for once a week with a total of four times. Thirty minutes before IR, mice were intraperitoneally injected with PD at the dose of 25mg/kg. The number and volume of CRC xenografts were calculated. Immunohistochemical staining was performed to detect the expression of Ki67 and cleaved caspase-3 in tumor tissues samples. The effects of PD on proliferation and apoptosis were evaluated in CT26 and HCT116 colon tumor cells. Leucine-rich repeat-containing G-protein coupled receptor 5 positive (Lgr5⁺) cancer stem cells (CSCs) were sorted from CT26 cells and the effects of PD on their proliferation and apoptosis were observed to elucidate the radiosensitizing mechanism of PD in CRC cells. Combined therapy with PD and IR significantly decreased tumor volume, inhibited proliferation and induced apoptosis of tumor cells in the mouse model of CRC compared to other three groups. Compared to the IR group, in vitro assay showed that PD combined with IR inhibited proliferation and promoted apoptosis of CT26 and HCT116 colon tumor cells as well as Lgr5⁺ CSCs. However, addition of the bone morphogenetic protein (BMP) type I receptor inhibitor K02288 (6.4nM) dramatically increased proliferation of Lgr5⁺ CSCs and abolished the cytotoxic effect of PD combined with IR on Lgr5⁺ CSCs. The in vivo and in vitro experiments demonstrated that IR combined treatment with PD could inhibit proliferation and promote apoptosis of CRC cells and Lgr5⁺ CSCs, and BMP signaling pathway was involved in the radiosensitizing effect of PD.

This study aimed to examine the radioprotective effect of polydatin (PD) on crypt and endothelial cells of the small intestines of C57BL/6 mice that received abdominal irradiation (IR). Mice were treated with 6 MV X-ray (20 Gy) abdominal IR at a dose rate of 200 cGy/min. Thirty minutes before or after IR, mice were intraperitoneally injected with PD. The rate of survival of the mice at 30 days after IR was determined. The duodenum (upper small intestine), jejunum (middle small intestine), and ileum (lower small intestine) were collected and subjected to hematoxylin and eosin staining. Tissue sample sections were analyzed through light microscopy, and the lengths of at least 20 intestinal villi were measured in each group; the average number of crypts was obtained from 10 intestinal samples in each group. Microvessel density was assessed using CD31-positive (brown) vascular endothelial cells/cell clusters. FHs74Int cell proliferation was measured using the CCK-8 assay. PD administration (25 mg/kg) before IR was the most effective in prolonging the survival of C57BL/6 mice. PD reduced radiation-induced injury of intestinal villi, prevented loss of crypts, increased intestinal crypt growth, protected against IR-induced intestinal injury, and enhanced the proliferative potential and reduced the apoptosis of FHs74Int cells after IR. Moreover, PD increased small intestinal MVD and reduced the apoptosis of intestinal microvascular endothelial cells in mice after IR. Therefore, PD was found to be able to protect the two types of cells from radiation damage and to thus alleviate radiation-induced injury of small intestine.

Tritium is a water-soluble hydrogen isotope that releases beta rays during decay. In nature, tritium primarily exists as tritiated water (HTO), and its main source is nuclear power/processing plants. In recent decades, with the development of nuclear power industry, it is necessary to evaluate the impact of tritium on organisms. In this study, fertilized zebrafish embryos are treated with different HTO concentrations (3.7 × 10³ Bq/ml, 3.7 × 10⁴ Bq/ml, 3.7 × 10⁵ Bq/ml). After treatment with HTO, the zebrafish embryos developed without evident morphological changes. Nevertheless, the heart rate increased and locomotor activity decreased significantly. In addition, RNA-sequencing shows that HTO can affect gene expressions. The differentially expressed genes are enriched through many physiological processes and intracellular signaling pathways, including cardiac, cardiovascular, and nervous system development and the metabolism of xenobiotics by cytochrome P450. Moreover, the concentrations of thyroid hormones in the zebrafish decrease and the expression of thyroid hormone-related genes is disordered after HTO treatment. Our results suggest that exposure to HTO may affect the physiology and behaviors of zebrafish through physiological processes and intracellular signaling pathways and provide a theoretical basis for ecological risk assessment of tritium.