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/pharmacologyABSTRACT
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-RaysABSTRACT
<p><b>OBJECTIVE</b>To study the pulmonary toxicity to rats induced by different sized SiOz particles.</p><p><b>METHODS</b>One hundred and five male SD rats were divided into seven groups randomly according to their weight. Experimental rats were exposed to 20, 50, 80, 140, 280 and 800 nm SiO2 particles at the dose of 400 mg/m3 by inhalation for 2 hours respectively. The control group was exposed without SiO2 particles. At the 24th, 48th, 72th hour after exposure, five rats were sacrificed at each time point and the total cellular scores, total protein, lactate dehydrogenase (LDH) in BALF and the histopathological changes in lungs were observed.</p><p><b>RESULTS</b>The total cellular score, total protein and lactate dehydrogenase in bronchoalveolar lavage fluid (BALF) of all experimental groups were higher than the control group. Between 800 nm group and the control group, there were no significant changes in total cellular sare, total protein and LDH in BALF (P > 0.05). At 48 h, the total cellular score of 280 nm group had no significantly change compared with the control group, but the total protein and LDH in BALF of 280 nm group were significantly higher than the control group (P < 0.05). The total cellular score at 24 h and the total protein at 24, 48 h had no significantly changes compared with the control group, but other indexes of 140 nm group were significantly higher than the control group. All the indexes of the 20, 50, 80 nm group were significantly higher than the control group (P < 0.05), and higher than 800 nm group mostly time. The TCS, total protein and LDH in BALF increased firstly and then reduced. The experimental group visible part pulmonary alveolus gap varying degree proliferation accumulation, its periphery has massive phlogocyte accumulation,such as granular cells and macrophage.</p><p><b>CONCLUSION</b>Under this condition ,the SiO2 particles can cause lung damage more serious with the smaller diameter SiO2 particles. As time going on, the damage caused by SiO2 particles is not so serious as before.</p>
Subject(s)
Animals , Male , Rats , Bronchoalveolar Lavage Fluid , Cell Biology , Cell Count , Inhalation Exposure , Lung , Metabolism , Pathology , Nanoparticles , Toxicity , Particle Size , Rats, Sprague-Dawley , Silicon Dioxide , ToxicityABSTRACT
<p><b>OBJECTIVE</b>To investigate the construction of oligonucleotide microarray specialized for pancreatic adenocarcinoma-associated genes and its application.</p><p><b>METHODS</b>Pancreatic cancer related genes were purposely selected, and oligonucleotide microarray was prepared by spotting oligonucleotide probes onto glass slides coated with APS-PDC. Total RNA were extracted from frozen tissues with TRIzol method according to the manufacturer's protocol, and purified with QIAGEN RNeasy Kit. Labeled cDNA targets for hybridizations were synthesized by reverse transcription from control- and cancer-total RNA samples in the presence of Cy5-dCTP and Cy3-dCTP, respectively. The labeled probes were hybridized with oligonucleotide microarray for 16 h to 18 h. Hybridized microarray was scanned by Agilent laser scanner, and the acquired image was analyzed by Imagene3.0 software. The intensity ratio of Cy3 and Cy5 were calculated. To confirm the expression profiles of these genes, quantitative reverse transcription-PCR (Q RT-PCR) was carried out with CDC25B and TUSC3 genes. The product of PCR were quantitated by comparative Ct method.</p><p><b>RESULTS</b>The signal of microarray hybridization was clear, and the images had a lower background and higher signal-noise ratio. The signal of positive control spots were uniform, and spots of negative control and blank signal were fairly low. In comparison with normal pancreas, 24 differential expressed genes were identified, which included 17 up-regulated and 7 down-regulated genes. The results of Q RT-PCR demonstrated that the expression of CDC25B and TUSC3 in pancreatic cancer were increased and decreased respectively, which consistent with microarray hybridization.</p><p><b>CONCLUSIONS</b>The oligonucleotide microarray specialized for pancreatic cancer are desirable for its specialty, flexibility and sensitivity, which can simultaneously and parallelly detect multiple pancreatic cancer-associated genes. In contrast to normal pancreatic tissues, the genes expression profile are different significantly in pancreatic cancer.</p>