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1.
Biomedical and Environmental Sciences ; (12): 437-447, 2022.
Article in English | WPRIM | ID: wpr-927682

ABSTRACT

Objective@#miR-663a has been reported to be downregulated by X-ray irradiation and participates in radiation-induced bystander effect via TGF-β1. The goal of this study was to explore the role of miR-663a during radiation-induced Epithelium-to-mesenchymal transition (EMT).@*Methods@#TGF-β1 or IR was used to induce EMT. After miR-663a transfection, cell migration and cell morphological changes were detected and the expression levels of miR-663a, TGF-β1, and EMT-related factors were quantified.@*Results@#Enhancement of cell migration and promotion of mesenchymal changes induced by either TGF-β1 or radiation were suppressed by miR-663a. Furthermore, both X-ray and carbon ion irradiation resulted in the upregulation of TGF-β1 and downregulation of miR-663a, while the silencing of TGF-β1 by miR-663a reversed the EMT process after radiation.@*Conclusion@#Our findings demonstrate an EMT-suppressing effect by miR-663a via TGF-β1 in radiation-induced EMT.


Subject(s)
Down-Regulation , Epithelial-Mesenchymal Transition , Epithelium/metabolism , MicroRNAs/metabolism , Transforming Growth Factor beta1/pharmacology
2.
Biomedical and Environmental Sciences ; (12): 419-436, 2022.
Article in English | WPRIM | ID: wpr-927681

ABSTRACT

Objective@#To investigate the function of primary cilia in regulating the cellular response to temozolomide (TMZ) and ionizing radiation (IR) in glioblastoma (GBM).@*Methods@#GBM cells were treated with TMZ or X-ray/carbon ion. The primary cilia were examined by immunostaining with Arl13b and γ-tubulin, and the cellular resistance ability was measured by cell viability assay or survival fraction assay. Combining with cilia ablation by IFT88 depletion or chloral hydrate and induction by lithium chloride, the autophagy was measured by acridine orange staining assay. The DNA damage repair ability was estimated by the kinetic curve of γH2AX foci, and the DNA-dependent protein kinase (DNA-PK) activation was detected by immunostaining assay.@*Results@#Primary cilia were frequently preserved in GBM, and the induction of ciliogenesis decreased cell proliferation. TMZ and IR promoted ciliogenesis in dose- and time-dependent manners, and the suppression of ciliogenesis significantly enhanced the cellular sensitivity to TMZ and IR. The inhibition of ciliogenesis elevated the lethal effects of TMZ and IR via the impairment of autophagy and DNA damage repair. The interference of ciliogenesis reduced DNA-PK activation, and the knockdown of DNA-PK led to cilium formation and elongation.@*Conclusion@#Primary cilia play a vital role in regulating the cellular sensitivity to TMZ and IR in GBM cells through mediating autophagy and DNA damage repair.


Subject(s)
Humans , Antineoplastic Agents, Alkylating/therapeutic use , Brain Neoplasms/metabolism , Cell Line, Tumor , DNA/therapeutic use , Glioblastoma/metabolism , Radiation, Ionizing , Temozolomide/therapeutic use
3.
Biomedical and Environmental Sciences ; (12): 126-135, 2018.
Article in English | WPRIM | ID: wpr-776072

ABSTRACT

OBJECTIVE@#To better understand the pathological causes of bone loss in a space environment, including microgravity, ionizing radiation, and ultradian rhythms.@*METHODS@#Sprague Dawley (SD) rats were randomly divided into a baseline group, a control group, a hindlimb suspension group, a radiation group, a ultradian rhythms group and a combined-three-factor group. After four weeks of hindlimb suspension followed by X-ray exposure and/or ultradian rhythms, biomechanical properties, bone mineral density, histological analysis, microstructure parameters, and bone turnover markers were detected to evaluate bone loss in hindlimbs of rats.@*RESULTS@#Simulated microgravity or combined-three factors treatment led to a significant decrease in the biomechanical properties of bones, reduction in bone mineral density, and deterioration of trabecular parameters. Ionizing radiation exposure also showed adverse impact while ultradian rhythms had no significant effect on these outcomes. Decrease in the concentration of the turnover markers bone alkaline phosphatase (bALP), osteocalcin (OCN), and tartrate-resistant acid phosphatase-5b (TRAP-5b) in serum was in line with the changes in trabecular parameters.@*CONCLUSION@#Simulated microgravity is the main contributor of bone loss. Radiation also results in deleterious effects but ultradian rhythms has no significant effect. Combined-three factors treatment do not exacerbate bone loss when compared to simulated microgravity treatment alone.


Subject(s)
Animals , Biomechanical Phenomena , Bone Density , Physiology , Bone Resorption , Metabolism , Femur , Metabolism , Hindlimb Suspension , Rats, Sprague-Dawley , Tibia , Metabolism , Ultradian Rhythm , Weightlessness Simulation , X-Rays
4.
Medical Journal of Chinese People's Liberation Army ; (12): 815-819, 2017.
Article in Chinese | WPRIM | ID: wpr-694048

ABSTRACT

Objective To investigate the protective effects of Angelica sinensis and Angelica sinensis polysaccharide against liver and kidney injury induced by irradiation of SD rats.Methods Thirty-two SD rats were randomly divided into four groups:control group,model group,Angelica decoction group and Angelica sinensis polysaccharide group.After 14 days of routine feeding,the rats were treated by intragastric administration once a day for 7 days.From the 8th day,the rats received whole body X-ray irradiation for 2 days.The total absorbed dose was 6Gy,and the dose rate was 92.26cGy/min.The rats were killed and the blood were collected from the femoral artery 3 days after irradiation.The content of superoxide dismutase (SOD),malondialdehyde (MDA),glutathione peroxidase (GSH-Px) and lipid peroxide (LPO) in the liver and kidney tissues was detected by colorimetric analysis.The pathological changes of the liver and kidney were observed by HE staining under microscope.The expression of Nrf2 protein in the liver and kidney of the rats was detected by Western blotting.Results Compared with control group,the weight of the liver and kidney significantly increased,the activities of SOD and GSH-Px significantly decreased,the contents of MDA and LPO significantly increased,and the liver and kidney cells showed obvious edema,and the content of Nrf2 in the liver and kidney increased in the model group.Compared with model group,the weight of the liver and kidney decreased,SOD and GSH-Px activities significantly increased,the contents of MDA and LPO significantly decreased,edema of the liver and kidney significantly reduced,the expression of Nrf2 in the liver and kidney tissues decreased in Angelica decoction group and Angelica sinensis polysaccharides group,while there was no difference between Angelica sinensis polysaccharide group and Angelica decoction group.Conclusion Angelica sinensis and Angelica polysaccharides have a good protective effect against liver and kidney injury induced by radiation in SD rats,which is implemented mainly through influencing the expression of free radicals.The protective effect of Angelica against radiation injury is achieved mainly by Angelica polysaccharide.

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