[Differential expressions of seminal plasma piRNAs in men and its significance].

OBJECTIVE: To study the differential expressions of piRNAs in the seminal plasma of men and the role of piRNAs in spermatogenesis. METHODS: We sequenced the seminal plasma samples collected from 187 male infertility patients and 58 normal healthy men, obtained differentially expressed piRNAs, and detected the relative expressions of piRNAs in different types of sperm by RT-qPCR to explore their significance in the diagnosis of male infertility. Using histopathology, RNA-protein pull-down and Western blot, we investigated the action mechanism of piRNAs in spermatogenesis in the mouse model. RESULTS: RT-qPCR of the seminal plasma samples revealed a high expression of hsa_piR_000478 in teratozoospermia and ROC curve analysis showed an auxiliary significance of hsa_piR_000478 in the diagnosis of the disease (AUC = 0.7549). Transfection of hsa_piR_000478 and its homologous sequence piR_mmu_54800729 into the seminiferous tubules of the mouse model significantly decreased sperm motility, increased the percentage of morphologically abnormal sperm and destroyed the testicular structure. Molecular biological experiments exhibited a close correlation between piRNAs and the energy metabolism-related pathway, which elevated the level of cell glycolysis and interfered with normal spermatogenesis. CONCLUSION: hsa_piR_000478 has an auxiliary significance in the diagnosis of male infertility, and piRNAs may interfere with spermatogenesis by affecting the glycolysis-related pathway in the spermatogenic microenvironment of the testis.

Integrative effects based on behavior, physiology and gene expression of tritiated water on zebrafish.

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.

C-Myc regulates radiation-induced G2/M cell cycle arrest and cell death in human cervical cancer cells.

AIM: The study was conducted to investigate the role of c-Myc in the regulation of ionizing radiation-induced cell cycle arrest and cell death in human cervical cancer cells. METHODS: Control and c-Myc-silenced Hela cells were collected at different time points after 60 Co γ-ray radiation. Flow cytometry was used to measure cell cycle distribution and apoptosis. Immunofluorescence was applied to determine the percentage of cells in M phase. Transmission electron microscopy and immunoblotting were used to detect the induction of autophagy after radiation. Immunoblotting was also used to measure the expression levels of apoptosis-related proteins. RESULTS: In c-Myc-silenced cells, radiation induced delayed but long-lasting G2/M arrest and an abnormal M phase compared with the control. In addition, c-Myc knockdown significantly inhibited apoptotic cell death induced by radiation. Meanwhile, radiation-induced autophagy appeared stronger in c-Myc-silenced cells. Mechanically, we found that Caspase 8 and survivin expression was decreased in c-Myc-silenced Hela-630 cells. CONCLUSIONS: These data showed that c-Myc serves as a co-regulator in radiation-induced G2/M cell cycle arrest and cell death in human cervical cancer cells.

The involvement of c-Myc in the DNA double-strand break repair via regulating radiation-induced phosphorylation of ATM and DNA-PKcs activity.

Deregulation of c-Myc often occurs in various human cancers, which not only contributes to the genesis and progression of cancers but also affects the outcomes of cancer radio- or chemotherapy. In this study, we have investigated the function of c-Myc in the repair of DNA double-strand break (DSB) induced by γ-ray irradiation. A c-Myc-silenced Hela-630 cell line was generated from HeLa cells using RNA interference technology. The DNA DSBs were detected by γ-H2AX foci, neutral comet assay and pulsed-field gel electrophoresis. We found that the capability of DNA DSB repair in Hela-630 cells was significantly reduced, and the repair kinetics of DSB was delayed as compared to the control Hela-NC cells. Silence of c-myc sensitized the cellular sensitivity to ionizing radiation. The phosphorylated c-Myc (Thr58/pSer62) formed the consistent co-localisation foci with γ-H2AX as well as the phosphorylated DNA-PKcs/S2056 in the irradiated cells. Moreover, depression of c-Myc largely attenuated the ionizing radiation-induced phosphorylation of the ataxia telangiectasia mutated (ATM) and decreased the in vitro kinase activity of DNA-PKcs. Taken together, our results demonstrated that c-Myc protein functions in the process of DNA double-strand break repair, at least partially, through affecting the ATM phosphorylation and DNA-PKcs kinase activity. The overexpression of c-Myc in tumours can account for the radioresistance of some tumour cell types.

Contrasting effects of Krüppel-like factor 4 on X-ray-induced double-strand and single-strand DNA breaks in mouse astrocytes.

Astrocytes, the most common cell type in the brain, play a principal role in the repair of damaged brain tissues during external radiotherapy of brain tumours. As a downstream gene of p53, the effects of Krüppel-like factor 4 (KLF4) in response to X-ray-induced DNA damage in astrocytes are unclear. In the present study, KLF4 expression was upregulated after the exposure of astrocytes isolated from the murine brain. Inhibition of KLF4 expression using lentiviral transduction produced less double-strand DNA breaks (DSB) determined by a neutral comet assay and flow cytometric analysis of phosphorylated histone family 2A variant and more single-strand DNA breaks (SSB) determined by a basic comet assay when the astrocytes were exposed to 4 Gy of X-ray radiation. These data suggest that radiation exposure of the tissues around brain tumour during radiation therapy causes KLF4 overexpression in astrocytes, which induces more DSB and reduces SSB. This causes the adverse effects of radiation therapy in the treatment of brain tumours.

Apoptosis, necrosis, and autophagy in mouse intestinal damage after 15-Gy whole body irradiation.

Enterocytes die during high-dose radiation exposure in radiation accidents. The modality of cell death has a profound effect on the therapeutic response. The ilea from mice with 15 Gy total body irradiation (TBI) were drawn, morphological features observed by hematoxylin and eosin staining and transmission electron micrographs. The biochemical features of mouse ileum presented with the structure were cleaved Caspase-3 (apoptosis marker), Light Chain 3 (LC3)-I's conversion to LC3-II (autophagy marker) and high mobility group box chromosomal protein 1's secretion (necrosis marker). Then, the autophagy inhibitor (3-methyladenine), caspase inhibitor (Z-VAD-FMK) or necrosis inhibitor (necrostatin) was used to prevent death. Apoptosis, autophagy and necrosis were all appeared in the ileum, but necrosis had the biggest size; the use of 3-methyladenine and Z-VAD-FMK prolong one day's life of the mice after 15 Gy TBI, necrostatin significantly extended the lifespan of 15 Gy irradiated mice (p < 0.05). The results suggest that the death of enterocytes could not be classified into one type of cell death but rather as 'mixed death.'

Radon-induced alterations in micro-RNA expression profiles in transformed BEAS2B cells.

Radon and its progeny are confirmed to be type I carcinogenic agents accounting for increased risks in 10% of observed lung cancers globally. However, the underlying carcinogenic mechanisms are largely unknown. In the present study, BEAS2B cells were directly exposed twice to 20,000 Bq/m(3) radon gas for 20 min once (first passage) and subsequently 10 times (fifth passage). The fifth-passage cells were then subcultured for 1 and 20 generations (named Rn5-1 and Rn5-20, respectively). Molecular mechanisms indicative of malignant transformation were assessed by determination of apoptosis, seroresistance, and microRNA (miRNA) expression profiles. The microRNA profiles were used to assess the functional annotations of the target genes. Data indicated an increased seroresistance and colony efficiency on soft agar, and enhanced apoptosis resistance in the Rn5-20 cells with significant differential expressions in some miRNA, including hsa-miR-483-3p, hsa-miR-494, hsa-miR-2115*, hsa-miR-33b, hsa-miR-1246, hsa-miR-3202, hsa-miR-18a, hsa-miR-125b, hsa-miR-17*, and hsa-miR-886-3p. Functional annotation demonstrated that these miRNA target genes were predominantly involved in the regulation of cell proliferation, differentiation, and adhesion during the process of malignant transformation, which is associated with signal pathways such as mitogen-activated protein kinase (MAPK), Int and Wg (Wnt), reactive oxygen species (ROS), nuclear factor κB (NF-κB), and other genes regulating cell cycles.

Identification and validation of diagnostic signature genes in non-obstructive azoospermia by machine learning.

Non-obstructive azoospermia (NOA) is a common cause of male infertility, and no specific diagnostic indicators exist. In this study, we used human testis datasets GSE45885, GSE45887, and GSE108886 from GEO database as training datasets, and screened 6 signature genes (all lowly expressed in the NOA group) using Boruta algorithm and Lasso regression: C12orf54, TSSK6, OR2H1, FER1L5, C9orf153, XKR3. The diagnostic efficacy of the above genes was examined by constructing models with LightGBM algorithm: the AUC (Area Under Curve) of both ROC and Precision-Recall curves for internal validation was 1.0 (p < 0.05). For the external validation dataset GSE145467 (human testis), the AUC of its ROC curve was 0.9 and that of its Precision-Recall curve was 0.833 (p < 0.05). Next, we confirmed the cellular localization of the above genes using human testis single-cell RNA sequencing dataset GSE149512, which were all located in spermatid. Besides, the downstream regulatory mechanisms of the above genes in spermatid were inferred by GSEA algorithm: C12orf54 may be involved in the repression of E2F-related and MYC-related pathways, TSSK6 and C9orf153 may be involved in the repression of MYC-related pathways, while FER1L5 may be involved in the repression of spermatogenesis pathway. Finally, we constructed a NOA model in mice using X-ray irradiation, and quantitative Real-time PCR results showed that C12orf54, TSSK6, OR2H1, FER1L5, and C9orf153 were all lowly expressed in NOA group. In summary, we have identified novel signature genes of NOA using machine learning methods and complete experimental validation, which will be helpful for its early diagnosis.

LC3 Accelerated Brain-Lung Axis Abscopal Effects after Fractionated Whole-Brain Radiation by Promoting Motoneurons to Secrete Periostin.

The effect of autophagy on the radiation-induced bystander effect (RIBE) in vivo is unclear. Here, the whole brains of microtubule-associated protein 1A/1B-light chain 3 (LC3) and C57BL/6 (B6) mice were irradiated once (10 Gy)(IR1), given 3 fractions in three weeks (IR3), or 6 fractions in six weeks (IR6). The median survival of LC3 mice was 56.5 days, and that of B6 mice was 65 days after IR6. LC3 mice showed more congestion and fibrosis in the lung after the IR3 and IR6 irradiation protocols than B6 mice. Quantitative proteomics of serum samples and lung RNA sequencing of the LC3 group showed that the common most clustered pathway of the IR3 group was the elastic fiber formation pathway, which contained Periostin (POSTN). POSTN in the motoneurons increased with increasing number of radiation fractions in LC3 mice. A 1 µg/g POSTN neutralizing antibody reduced the lung fibrosis of LC3 mice exposed to IR3 by one-third, and significantly prolonged the survival time of LC3 mice exposed to IR6. LDN-214117 and LRRK2-in-1 were the best two of sixteen transforming growth factor-beta1 (TGF-ß) receptor and autophagy mediators to decrease Postn mRNA. These data led us to conclude that LC3 accelerated motoneuron secretion of POSTN and aggravated the RIBE in the lung after brain irradiation.

Novel treatment and insight for irradiation-induced injuries: Dibucaine ameliorates irradiation-induced testicular injury by inhibiting fatty acid oxidation in primary Leydig cells.

BACKGROUND: Male infertility is a worldwide problem but few treatments, especially irradiation-induced testicular injury. The aim of this research was to investigate novel drugs for the treatment of irradiation-induced testicular injury. METHODS: We administered dibucaine (0.8 mg/kg) intraperitoneally to male mice (6 mice per group) after five consecutive daily 0.5 Gy whole-body irradiation, and evaluated its ameliorating efficacy by testicular HE staining and morphological measurements. Drug affinity responsive target stability assay (Darts) were used to find target protein and pathway; mouse primary Leydig cells were isolated and to explore the mechanism (Flow cytometry, Western blot, and Seahorse palmitate oxidative stress assays); finally rescue experiments were completed by combining dibucaine with fatty acid oxidative pathway inhibitors and activators. RESULTS: The testicular HE staining and morphological measurements in dibucaine treatment group was significantly better than that in irradiation group (P < 0.05); sperm motility and mRNA levels of spermatogenic cell markers were also higher than those in the latter (P < 0.05). Darts and Western blot results showed that dibucaine targets CPT1A and downregulate fatty acid oxidation. Flow cytometry, Western blot, and Palmitate oxidative stress assays of primary Leydig cells demonstrated that dibucaine inhibits fatty acid oxidation in Leydig cells. Dibucaine combined with etomoxir/baicalin confirmed that its inhibition of fatty acid oxidation was beneficial in ameliorating irradiation-induced testicular injury. CONCLUSIONS: In conclusion, our data suggest that dibucaine ameliorates irradiation-induced testicular injury in mice by inhibiting fatty acid oxidation in Leydig cells. This will provide novel ideas for the treatment of irradiation-induced testicular injury.

Exosome-coated polydatin nanoparticles in the treatment of radiation-induced intestinal damage.

This study aimed to develop an exosome-coated polydatin (PD) nanoparticles (exo-PD) for improving the water solubility and bioavailability of polydatin and explore its salutary effects on intestinal radiation injury. Exosomes (exo) were extracted from the medium of human amniotic fluid stem cells (hAFSc). Mice were divided into control group, irradiation (IR) group, irradiation+PD (IR+PD) group, irradiation+exo (IR+exo) group and irradiation+exo-PD (IR+exo-PD) group. The results of characterization of protein markers, particle size, morphology and cellular uptake ability confirmed that exosomes were effectively isolated using ultracentrifugation. Compared with the IR group, exo-PD improved cell viability, prolonged survival of mice, improved leukocyte count and reduced diarrhea rate. Histological results showed that the exo-PD group had significant improvements in small intestinal villus length and crypt number and less crypt cell damage. exo-PD could reduce IL-1α and IL-6 levels, reduced γ-H2AX expression, increased mitochondrial membrane potential, enhanced oxidative phosphorylation, and delayed cellular senescence. exo-PD could alleviate intestinal injury by improving mitochondrial function through PI3K-AKT pathway. The exo-PD was able to reduce radiation damage to intestinal cells and could be a potential candidate for salvage of intestinal radiation damage.

Radiation Protection of Polydatin Against Radon Exposure Injury of Epithelial Cells and Mice.

Radon exposure is significantly associated with lung cancer. Radon concentration is currently reduced mainly by physical methods, but there is a lack of protective drugs or biochemical reagents for radon damage. This study aimed to explore the protective effect of polydatin (PD) on the radon-exposed injury. The results showed that PD can significantly reduce ROS level, raise SOD activity, weaken the migration ability, increase E-cad, and decrease mesenchymal cell surface markers (FN1, Vimentin, N-cad, α-SMA, and Snail) in radon-exposed epithelial cells. In vivo, PD increased the mice weight, promoted SOD activity, and decreased MDA content, the number of bullae, pulmonary septum thickness, lung collagenous fibers, and mesenchymal cell surface markers. Furthermore, PD inhibited p-PI3K, p-AKT, and p-mTOR expression. Compared with directly adding PD on radon-exposed cells, adding PD before and after radon exposure could more obviously improve the adhesion of radon-exposed cells, significantly alleviate the migration ability, and more significantly reduce mesenchyme markers and p-AKT and p-mTOR. These results indicate that PD can reduce oxidative stress, weaken epithelial-mesenchymal transition (EMT) and lung fibrosis in radon-exposed cells/mice, and have good radiation protection against radon injury. The mechanism is related to the inhibition of the PI3K/AKT/mTOR pathway.

Improving effects of telmisartan on spermatogenic disorder induced by fractionated low-dose irradiation in mice.

BACKGROUND: Male infertility is a hot problem worldwide, but there are few treatments, especially male infertility caused by irradiation is difficult to treat. The aim of this study was to investigate and evaluate novel drugs for the treatment of male infertility caused by irradiation. METHODS: we randomly divided 18 male BALB/c mice into 3 groups: control, irradiated, and telmisartan. Both irradiated and telmisartan group completed whole-body 0.5 Gy five times irradiation, and the telmisartan group received intraperitoneal injection of telmisartan (1.2 mg/kg) daily on the next day after irradiation, and all groups were sampled on day 25 after irradiation. RESULTS: Sperm motility results show that total sperm motility of irradiated group was significantly lower compared with control group, and testicular HE results showed that testis in irradiated group were severely damaged. Compared with irradiated group, the total sperm motility, sperm concentration, testicular index, Johnsen score, and the seminiferous tubule layer numbers were higher in telmisartan group (P < 0.05). The immunohistochemical staining showed γ-H2AX expression is higher in telmisartan group compared with irradiated group. And the relative mRNA expression of PLZF, GFRA1, STRA8, DMRT1, SPO11, SYCP2, OVOL2, CCNA1, TJP3, RUNX2, TXNDC2 TNP1, and PRM3 in telmisartan group was all significantly higher than irradiated group (P < 0.05). CONCLUSION: In conclusion, in vivo experiments confirmed that telmisartan ameliorated the spermatogenic disorder in mice caused by fractionated low-dose irradiation via promoting spermatogenesis.

Quinacrine Inhibits Cell Growth and Induces Apoptosis in Human Gastric Cancer Cell Line SGC-7901.

BACKGROUND: Quinacrine (QC), an antimalarial drug, has been shown to possess anticancer effect both in vitro (cancer cell lines) and in vivo (mouse models). In the cancer cells, QC can simultaneously suppress nuclear factor-κB and activate p53 signaling, which results in the induction of the apoptosis in these cells. However, the experimental results come from a few limited cancer cell lines, and the detailed mechanisms remain unknown. OBJECTIVE: This study investigated the tumor-killing effects of QC on gastric cancer cells as well as underlying molecular pathways. METHODS: SGC-7901 cells were treated with or without QC at different concentrations for 24 hours. The effect of QC on the inhibition of SGC-7901 cell proliferation was assessed by Cell Counting Kit-8 assay. Apoptosis was detected by examining nuclear morphology and quantifying phosphatidylserine externalization. Alterations in cellular morphology were analyzed by laser scanning confocal microscopy for fluorescent analysis. Cell cycle analysis was performed by propidium iodide (PI) staining and flow cytometry. The enzyme activity changes of caspase-3 were detected by colorimetry expression method. Western blot analysis was used to detect the changes in the protein level of Bax, Bc1-2, p53, and cytochrome c in cytosol of SGC-7901 cells. RESULTS: Our results showed that QC could significantly inhibit the growth of SGC-7901 cells in a dose-dependent manner, with the IC50 mean (SD) value of 16.18 (0.64) µM, compared with nontreated controls. QC treatment (15 µM) could also induce apoptosis in SGC-7901 cells (26.30% [5.31%], compared with control group of 3.37% [0.81%]; P < 0.01), and the increasing phosphatidylserine level and the accumulation of chromatin nucleation in QC-treated cells provided further evidence. In addition, cell cycle analysis with PI staining showed that a significant S enriches, increasing from 12.00% (1.24%) (control) to 20.94% (2.40%) (QC treatment) (P < 0.01). Furthermore, increased activities of caspase-3 (increasing from 0.108 [0.019] to 0.628 [0.068]; P < 0.01) were observed in SGC-7901 cells treated with 15 µM QC. Western blot analysis showed that QC treatment significantly increased the levels of proapoptotic proteins, including cytochrome c, Bax, and p53, and decreased the levels of antiapoptotic protein Bcl-2, thus shifting the ratio of Bax/Bcl-2 in favor of apoptosis. CONCLUSIONS: Our findings suggest that QC can significantly inhibit cell growth and induce apoptosis in SGC-7901 cells, which involves p53 upregulation and caspase-3 activation pathway.

Analysis of circRNA-miRNA-mRNA Regulatory Network in Peripheral Blood of Radiation Workers.

The health of radiation workers has always been our focus. Epidemiological investigation shows that long-term exposure to low-dose ionizing radiation can affect human health, especially cancer and cardiovascular disease, and there are many studies on it. However, up to now, there have been few reports on the research of blood and biological samples from radiation workers. In this study, radiation workers and healthy control groups were strictly screened, and the transcriptome of mRNA and circRNA was sequenced by extracting their peripheral venous blood. At the same time, appropriate data sets were selected in the GEO database for bioinformatics analysis, and circRNA-miRNA-mRNA network was constructed. We identified 9 different circular ribonucleic acids, 3 tiny ribonucleic acids, and 2 central genes (NOD 2 and IRF 7). These differentially expressed genes and non-coding RNA are closely related to ionizing radiation damage, and play an important role as biological markers. In conclusion, this study may provide new insights into the role of the circRNA-miRNA-mRNA regulatory network in the health of radiation workers, and provides a new strategy for the future study of radiation biology.

Protective Effects of Polydatin on Reproductive Injury Induced by Ionizing Radiation.

The reproductive system is vulnerable to ionizing radiation, which is a hot research topic at present. We tested the effect of polydatin on spermatocytes(GC-1 cells) after X-ray irradiation. The reproductive damage model of C.elegans was established by 60Coγ-ray, and the protective effect of polydatin on reproductive damage caused by ionizing radiation was evaluated. We quantified the ROS levels of GC-1 cells and C.elegans after irradiation with polydatin and evaluated the anti-apoptosis effect of polydatin at proper concentration. Differential genes of C.elegans reproductive damage were screened out from transcriptome sequencing results and comparable GEO datasets. It was proved that 100µM polydatin significantly reduced the apoptosis of GC-1 cells induced by 2 Gy X-ray. In addition, the longevity, reproductive capacity, germ cell apoptosis and spawning and hatching capacity of polydatin were tested. The results showed that 100 µM polydatin content significantly increased the influence of 50 Gy 60Coγ-ray on reproductive capacity of C.elegans. Quantitative analysis of mRNA and protein levels of apoptosis-related genes and reproductive-related genes by qRT-PCR and Western blotcon firmed that polydatin with appropriate dosage had good protective effects on reproductive damage caused by radiation, which laid a foundation for the application research of polydatin in radiation protection.

Proteomic and miRNA profiling of radon-induced skin damage in mice: FASN regulated by miRNAs.

Radon is a naturally occurring radioactive gas and considered as a serious carcinogen to humans. Continuous radioactive decay of this gas emits high-energy alpha particles. Long-term radon exposure induces oxidative stress and inflammatory response, which results in chronic lung diseases. However, biological effects after radon exposure in other organs have been rarely reported. As the outermost organ of the human body, the skin suffers from environmental damage to agents such as air pollution. Epidemiological studies indicated that areas with high level of radon had a high incidence of skin cancer. However, whether radon exposure induces skin damage has not been reported yet. In this study, we established a radon-exposed mouse model and found that radon exposure affected the structure of skin tissues, which was manifested by inflammatory cell infiltration and skin atrophy. Using proteomic approach, we found 45 preferentially expressed proteins in 60 Working Level Months (WLM) group and 314 preferentially expressed proteins in 120 WLM group from radon-exposed skin tissues. Through microRNA (miRNA) sequencing profiling analysis, 57 dysregulated miRNAs were screened between the control and radon-treated mouse skin. By integrating the dysregulated proteins and miRNAs, radon-induced fatty acid synthase (FASN) was investigated in greater detail. Results showed that FASN was regulated by miR-206-3p and miR-378a-3p and involved in the pathogenesis of radon-induced skin damage. Overexpression of FASN inhibited the proliferation, and induced in WS1 cells. Our present findings illustrate the molecular change during radon-induced skin damage and the potential role of FASN during this process.

Puerarin Reduces Radiation-Induced Vascular Endothelial Cell Damage Via miR-34a/Placental Growth Factor.

The aim is to explore the protective effects of Puerarin on radiation-induced vascular endothelial cell damage and its underlying mechanism. The apoptosis and DNA damage of Human umbilical vascular endothelial cells (HUVECs) exposed to radiation alone or in combination with glucose in the exposed group were significantly elevated (P < .05) compared with those in the control group. The Puerarin-treated HUVECs showed significant reduction in the radiation-induced apoptosis and DNA damage (P < .05). Furthermore, X-ray irradiation significantly increased the expression of miR-34a, which was reversed by pre-treatment with Puerarin. Placental Growth Factor (PLGF) was a target gene of miR-34a. The expression of PLGF in the peripheral blood of patients receiving radiotherapy significantly increased with an increase in the cumulative dose of radiation (P < .05), after which it began to decrease at the fourth week (P < .05) and then remained at a low level until the end of radiotherapy. Puerarin exerts a radioprotective effect by decreasing DNA damage and apoptosis through miR-34a-targeted PLGF.

Monte Carlo determination of dose coefficients at different developmental stages of zebrafish (Danio rerio) in experimental condition.

The release of liquid effluent of nuclear power into aquatic system increases with the rapid development of nuclear facilities in coastal and inland regions. Aquatic model animals are very important for the study of the radiation hazards to non-human biota in water environment and its extrapolation of dose-effect relationship to human models. However, the study of the radiation dose rate calculation model of the aquatic animal zebrafish is still on the homogeneous isotropic model used for the protection of the environment. A series of zebrafish models (including adults, larvae and embryos, named zebrafish-family: ZF-family) with multiple internal organs are established in this study to investigate the mechanism of radiation damage effect in order to protect non-human species. The internal and external dose coefficients (DCs) of the whole body, heart and gonads of zebrafishes are calculated in water environment with the combination of the real experimental culture condition, using Monte Carlo application package GATE (Geant4 Application for Emission Tomography) and eight nuclides, i.e., 3H, 14C, 90Sr, 60Co, 110mAg, 134Cs, 137Cs, 131I, which are commonly found in the liquid effluent of nuclear power plants, as the source items, The results show that the level of nuclide γ energy determines the external DCs (DCext), and 90Sr plays the most important role in internal DCs (DCint). The comparison between the external DCs of the heart and gonad and that of the whole body shows that DCs (DCext) of heart and gonad for females are 80% and 43% lower than that of whole body, respectively, while for males, the DCs (DCext) of heart is 44% lower than that of the whole body, and DCs (DCext) of gonad is slightly higher than that of the whole body for most nuclides (up to 25%).The dose of internal radiation makes greater contribution than that of external radiation to pure beta emitter (3H, 14C, 90Sr). This internal DCs of ZF-family model with complex internal structure turns out to demonstrate more sensitive DCs change trend and higher calculation values compared with the internal DCs of the simple ellipsoid model. In this model, the photon emitter with strong penetrating power has higher internal DCs, while the low-energy pure beta nuclide does not alter much. In conclusion, it is vital to carry out refined systematic modeling for model organisms, and the determination of DCs of model organs can promote the evaluation of the radiation effects on non-human species.

Development and Characterization of a Novel Hydrogel for the Decontaminating of Radionuclide-Contaminated Skin Wounds.

Designing skin decontaminating materials with outstanding therapeutic effects, adhesiveness, and suitable mechanical property has great practical significance in radionuclide-contaminated skin wound healing. Here, a physically crosslinked hydrogel is constructed via hydrogen bonding of poly acrylamide, sodium alginate (SA), and the complexing agent diethylene triamine pentaacetic acid (DTPA). The physical and chemical properties of the poly(AAm-SA-DTPA) hydrogel (PASD) are detected according to established methods. The decontaminating property and skin wound healing of the PASD are investigated to confirm multi-functions of wound dressing. The physical and chemical properties results show that the synthesis of the PASD hydrogel is effective and that DTPA is present in the hydrogel. The hydrogel also shows great mechanical and swelling properties. In vitro tests find that PASD shows significant scavenging abilities for strontium and cerium. In vivo experiments show that the PASD hydrogel can remove radioactive strontium from the skin wounds of mice, and can effectively prevent the absorption of radioactive strontium through the skin wound. Furthermore, the PASD hydrogel can effectively promote the formation of granulation tissue in a radioactive contaminated wound. Taken together, the PASD hydrogels, which has good mechanical properties and radionuclides decontamination, is expected to be used as a dressing for radionuclide-contaminated skin wound healing.