Gingival mesenchymal stem cells inhibited senescence of type Ⅱ alveolar epithelial cells and prevented radiation-induced pulmonary fibrosis / 中华放射医学与防护杂志

Objective:To investigate whether transplantation of gingival mesenchymal stem cells (GMSCs) can inhibit radiation-induced senescence of alveolar epithelial cells type Ⅱ (AECⅡ) and its role in the prevention of radiation-induced pulmonary fibrosis (RIPF).Methods:Mouse type Ⅱ alveolar epithelial cells (MLE12) were irradiated with 6 Gy X-rays and then co-cultured with GMSCs. The extent of cellular senescence of MLE12 cells was assessed by cell morphology, β-Gal staining, and senescence secretion-associated phenotype (SASP) assay. RIPF model was constructed by unilaterally irradiating the right chest of C57BL/6 mice with 17 Gy X-rays. GMSCs were transplanted 1 d after irradiation. At 180 d after irradiation, the pulmonary organ ratio, HE staining, and Masson staining were used to assess intra-pulmonary structure and interstitial collagen deposition in the lung. β-Gal immunohistochemistry and immunofluorescence co-localization with AECⅡ were measured to assess the degree of cellular senescence in the lung. The SASP expression changes in lung tissue were detected by qRT-PCR. The protein expressions in P53-P21 and P16 pathways were detected by Western blot assay. P21 expression in AECⅡ was detected by immunofluorescence co-localization assay.Results:GMSCs effectively inhibited radiation-induced senescence of MLE12 cells, reduced the ratio of radiation-elevated β-Gal positive cells by 11.8% ( t=6.72, P<0.05), and decreased the expressions of SASP (IL-6, IL-8, IL-1β) ( t=28.43, 28.43, 4.82, P<0.05). GMSCs transplantation improved the survival rate of irradiated mice, prevented radiation-induced alveolar structural collapse thickening and collagen deposition, reduced the number of senescent cells in the irradiated lung tissues by 23.9% ( t=21.83, P<0.05), and inhibited the expressions of SASP ( t=8.86, 20.63, P<0.05). GMSCs also inhibited the expression of P53-P21, P16-related proteins in MLE12 cells and lung tissues of mice after irradiation. Conclusions:GMSCs inhibit senescence-related P53-P21 and P16 pathways, prevent radiation-induced AECⅡ senescence, as well as the development of RIPF.

Role of umbilical cord mesenchymal stem cell transplantation in alleviating alveolar cell senescence / 中国辐射卫生

Objective@#To investigate whether the transplantation of umbilical cord mesenchymal stem cells (UC-MSCs) can alleviate radiation-induced pulmonary fibrosis (RIPF) and attenuate intrapulmonary cellular senescence in mice with RIPF.@*Methods@#The C57BL/6 mice were unilaterally irradiated with 17 Gy in the right lung to construct RIPF models. UC- MSCs were injected into the caudal vein at 3 months after radiation, and samples were taken at 6 months. The survival rate of mice was recorded, and the lung organ ratio was calculated. Lung structure and collagen deposition were observed by hem- atoxylin-eosin  staining  and  Masson  staining.  The  expression  of  senescence  secretion-associated  phenotype  (SASP)  was measured by quantitative real-time polymerase chain reaction. Intrapulmonary cellular senescence was assessed by β-Gal im- munohistochemistry. The expression of key proteins in the P53-P21 and P16 pathways was measured by Western blot. P21 expression in the lung was measured by tissue immunofluorescence.@*Results@#Compared with the untreated group, RIPF mice treated with UC-MSCs showed an improved survivalrate, reduced collagen deposition, and an improvement incollapse and thickening of alveolar structure. Increased β-Gal-positive senescent cells and high expression of SASP (IL-6, IL-8, IL- 1β) in the lung of RIPF mice were all reduced after UC-MSC treatment. The abnormally increased levels of P53, p-P53, P21 and P16 proteins in RIPF mice were reduced by UC-MSC treatment.@*Conclusion@#UC-MSCs may reduce cellular senes- cence in fibrotic lungs and alleviate RIPF by inhibiting P53-P21 and P16 pathways, which is expected to be used for the treatment of radiation-induced lung injury.

Progress in the treatment of radiation-induced pulmonary fibrosis with mesenchymal stem cells / 中华放射医学与防护杂志

Radiation-induced pulmonary fibrosis (RIPF) is a common complication of thoracic tumor radiotherapy. The main manifestation of radiation-induced pulmonary fibrosis is chronic progressive consolidation of pulmonary interstitium, which may cause the lung physiology function reduced or even lost. Furthermore, it can be lethal forrespiratory failure in severe cases. Recent studies have found that mesenchymal stem cells (MSC) play an important role in the modulation of proliferation and the activation of immune cells in lung inflammation. In addition, MSC can also play a part in the treatment of RIPF by differentiating into functional cells and secreting cytokines. Therefore, MSC has a good application prospect in RIPF as a cell therapy method. This article reviews the molecular mechanisms, influencing factors and current status of MSC therapy in RIPF.

Research progress of SUMOylation modification in DNA double-strand break repair / 国际生物医学工程杂志

The small ubiquitin-like modified protein (SUMO) is a protein structurally similar to ubiquitin which is involved in post-translational modification of proteins. SUMOylation refers to the process that SUMO molecule covalently binding to the specific lysine site of target proteins through maturation, activation, binding and ligation by ubiquitin-like specific protease 1 (Ulp1), E1 activating enzyme, E2 binding enzyme, and E3 ligase. SUMOylation alters the activity of target proteins, which is involved in the regulation of various cellular functions such as transcriptional regulation, regulation of embryonic development, cellular stress, maintenance of chromatin structure and genomic stability. In recent years, it has been found that SUMOylation modification is also widely involved in DNA damage repair, especially DNA double-strand breaks (DSBs), which are the most serious types of DNA damage. SUMOylation is involved in almost all processes of DSBs repair, so its role in DNA damage repair has become a research hotspot. In this paper, the research progress of the regulation of SUMOylation in DSBs repair was reviewed.

Study on the exposure of polychlorinated biphenyl contamination and DNA methylation in male employees in an e-waste dismantling area in Tianjin / 中华预防医学杂志

Objective@#To study on the exposure of polychlorinated biphenyl (PCB) contamination and DNA methylation in male employees in an e-waste dismantling area in Tianjin.@*Methods@#In 2016, an e-waste dismantling area in Tianjin and an area 50 km away from the e-waste dismantling area (no e-waste or other chemical, industrial and agricultural pollution nearby) were selected as the study area and the reference area. Male residents of the study area and male farmers who planted vegetables, fruits, and crops in the reference area were selected as the exposed and reference group by using the convenient sampling method. A total of 60 subjects (30 in each of the exposed group and the reference group) were included. The peripheral blood (5 ml) of the study subject was collected, and the PCB concentration was detected. Eight independent subjects in the exposed group and the reference group were randomly selected by random number table method to detect the methylation level of the promoter region of all gene loci, and the mRNA transcript levels.@*Results@#The PCB concentration in peripheral blood of the exposed group was higher than that of the reference group, and the difference was statistically significant (allP values <0.001). The methylation levels of the promoter region of the exposed group and the reference group showed obvious clustering, and 994 gene loci had different degrees of methylation. Compared with the reference group, there were 391 hypomethylation sites and 553 hypermethylation sites in the exposed group. The proportion of methylation sites in the high CpG-rich region was 59.2% and 48.1%, respectively. The mRNA level of the hypomethylated gene in the exposed group was higher (FAM131A, HBM), and the transcription level of the hypermethylated gene was lower (CAPN15, NFIC, SHISA5, FGF13, GRAMD1A, CLEC3B, LILRB2, DCAF7). The mRNA transcription levels of 10 genes above in the exposed group and the reference group were statistically significant (all P values <0.001).@*Conclusion@#The PCB concentration of peripheral blood in the exposed population of e-waste is high. PCB exposure changes the methylation level of specific genes and affects the mRNA transcription level of some genes.

Study on genomic stability of male workers in an e-waste dismantling area in Tianjin / 中华预防医学杂志

Objective@#To study on the genomic stability of male workers engaged in e-waste dismantling area in Tianjin.@*Methods@#In 2016, an e-waste dismantling area in Tianjin and an area 50 km away from the e-waste dismantling area (no e-waste or other chemical, industrial and agricultural pollution nearby) were selected as the study area and the reference area. Male residents of the study area and male farmers who planted vegetables, fruits, and crops in the reference area were selected as the exposed and reference group by using the convenient sampling method. The exposed group included 146 workers who engaged in e-waste recycling work more than 1 year. The reference group included 121 farmers who never engaged in e-waste recycling work. Questionnaires were used to collect information of all subjects. The semen and peripheral blood were also collected. Trace elements and polychlorinated biphenyl concentration in blood were detected. DNA damage in peripheral blood and sperm was detected, and gene expression was analyzed. DNA damage was assessed using tail DNA% (TDNA%), tail moment (TM) and olive tail moment (OTM) of comet assay.@*Results@#The ages of the exposed group and the reference group were (33.6±12.1) and (33.9±11.9) years old, respectively. The proportions of subjects with exposure time of ≤3, 4-6, ≥7 years were 43% (63 cases), 26% (53 cases) and 21% (30 cases), respectively. The Pb and polychlorinated biphenyl(PCB) concentrations in the exposed group [(90.4±15.3) μg/ml and (101±30) ng/ml, respectively] were higher than those in the reference group [Pb and PCB concentrations were (60.2±8.9) μg/ml, and (2.5±1.4) ng/ml, respectively (both P values <0.05)]. The TDNA%, TM and OTM of peripheral blood and sperm in the exposed group were 5.9%±0.3% and 2.6%±0.90%, 0.93±0.16 and 0.51±0.20, 0.82±0.09 and 0.56±0.07, respectively, which were all higher than those in the reference group [TDNA%, TM and OTM of peripheral blood and sperm were 1.8%±0.2% and 1.9%±0.2%, 0.21±0.04 and 0.32±0.10, 0.19±0.03 and 0.20±0.08, respectively (all P values <0.001)]. The results of gene expression showed that 20 differentially expressed genes, including 13 up-regulated genes and 7 down-regulated genes, were detected in the exposed group compared with the reference group.@*Conclusion@#There are obvious DNA damage and DNA repair gene disorder in male workers of an e-waste dismantling area in Tianjin. The current operation mode brings potential health risks to workers.

Research progress of new nanodrug AGUIX for radiosensitization / 国际生物医学工程杂志

In order to effectively improve the radiation sensitivity of tumors and reduce the side effects during radiotherapy,people have been working on the development of radiation sensitizers.In recent years,many researches focused on the nanoparticles with high atomic number elements as radiosensitizers.Researchers have recently developed a kind of new gadolinium-based radiation-sensitizing nanoparticles,i.e.AGUIX,which have low toxicity,low quality,and radiation-activated drug activity.These nanoparticles are consisted by a polysiloxane core and a network of covalently attached gadolinium chelates.They have a hydrodynamic diameter of less than 5 nm,and can be administered intravenously due to the preferential accumulation in tumor sites and elimination by kidney.Studies have proved that AGUIX can be used as a safe and effective radiation sensitizer under various irradiation conditions.In addition,due to the presence of strontium,AGUIX itself can also be used as a MRI contrast agent to monitor the biodistribution of drugs and tumor evolution,and then guide the development of radiotherapy.In this paper,the research progress of AGUIX in recent years was reviewed.

Bax protein structure and related research progress of eutectic structure / 国际生物医学工程杂志

Apoptosis involves multiple signaling pathways. The intrinsic signaling pathway is the mitochondrial apoptotic pathway, which is caused by a series of processes. First, the pro-apoptotic factors such as Bax are activated by signaling molecules and transfer to the mitochondrial outer membrane forming protein pores, thus the mitochondrial membrane permeability is affected, and then the downstream caspase-9 is activated and the apoptosis initiation is induced by releasing cytochrome C. In order to explore the apoptosis initiation activated by small molecules, the specific structural changes of Bax in apoptosis were studied. The results showed that there is a hydrophobic pocket structure near the C-terminal S184 of the Bax protein. This structure can be combined with certain small molecular substances specifically remove phosphorylation S184, and regulate Bax protein to promote apoptosis activity. At present, the nuclear magnetic structure of Bax protein has been obtained and the crystal structure has not been revealed. The eutectic structure formed by corresponding with other proteins in the Bcl-2 family has been resolved, which can be used to study the interactions between proteins and to understand the specific structural changes in the formation of heterologous dimers during apoptosis, site changes, etc. In this paper, the Bax protein structure resolved by nuclear magnetic structure was reviewed to learn the change of the sites in the induced apoptosis so as to promote the research on apoptosis initiation.

Research of radiation resistance delivery through paracrine effects on non-small cell lung cancer / 国际生物医学工程杂志

Objective To investigate the role and possible mechanisms of paracrine in radiation tolerance of non-small cell lung cancer (NSCLC) by observing the effects of radiation-resistant NSCLC H460R cell secretion on the radiosensitivity of parental H460 cells. Methods H460 cells were inoculated and cultured, and then divided into control group, conditional culturing group, irradiation group and irradiation combined conditional culturing group. One-time irradiation with 137Cs γ-rays was conducted with a dose rate of 1.02 Gy/min. Effect of H460R conditioned media on the radiation sensitivity of H460 cells was observed by clonogenic assay. The percentage of phospho-histone histone H2AX (γH2AX) positive cells was detected by immunofluorescence staining. The cyclical changes of the cells were detected by flow cytometry. The expression of DNA damage-associated proteinsγH2AX and Rad51 were detected by Western Blot. Results The results showed that compared with the singleγ-rays irradiation, the number of cell clones was significantly increased in the H460R cells after γ-rays irradiation combined with conditional culturing treatment at different doses of 2, 4, and 6 Gy, and the differences were statistically significant (2,4 Gy:all P<0.05;6 Gy:P<0.01). The results of immunofluorescence staining showed that the percentage ofγH2AX positive cells in the conditional culturing group was higher than that in the control group [(39.40±2.51)％vs. (25.21± 2.05)％], and the difference was statistically significant (P<0.01). This value in the irradiation combined conditional culturing group was lower than that in irradiated group [(60.48±2.79)％vs. (80.65±2.05)％], and the difference was statistically significant (P<0.001). The flow cytometry analysis showed that the percentage of cells in G2/M phase for the irradiation (4 Gy) combined conditional culturing group was higher than that of irradiated group [(26.83± 1.42)％ vs. (15.73±1.29)％], and the difference was statistically significant (P<0.001). The Western Blot results showed that γH2AX and Rad51 protein expression in the irradiation (4 Gy) combined conditional culturing group respectively was lower and higher than that in irradiated group. Conclusion In the tumor microenvironment, radiation-resistant H460R cells can enhance the radioresistance of H460 cells by paracrine, which may be related to the promotion of DNA repair ability after irradiation

Radioprotective effects of resveratrol and its mechanism / 中华放射医学与防护杂志

Resveratrol is a kind of natural active substance,which has strong antioxidant activity and radioprotective effect.A large number of tests have shown that resveratrol can attenuates radiation damage and play an important role in radiation protection,has a good application prospects.This paper reviews the radioprotective effects of resveratrol on the hematopoietic system,the immune system,the nervous system,the respiratory system,and other devices and their mechanisms of action.Including the HO1 signaling pathway,Nrf2 pathway and other antioxidant mechanisms and the activation of Sirt1 regulate the downstream signals,promote TyrRs into the nucleus to play the role of radioprotection.The prospect of application of resveratrol was also prospected.

The dynamic changes of gene expressions in radiation-injured intestine based on RNA-sequence analysis / 中华放射医学与防护杂志

Objective To investigate the dynamic changes of gene expressions in mouse jejunum after lethal dose abdomen irradiation (ABI).Methods RNA was extracted from mouse jejunum at 0 and 6 h,3.5 and 5 d after 14 Gy 137Cs γ-ray ABI and then subjected to RNA-sequence analysis.Gene with expressions changed more than 2-fold of control were identified as differentially expressed ones.The selected genes were subsequently analyzed using IPA,Funrich,GO and KEGG software.Results Gene analysis of mouse jejunum samples showed that radiation activated p53 pathway at 6 h and 3.5 d after ABI.Interaction network analysis of genes suggested that Lck,Cdkl and Fyn,genes could play an important role in jejunum damage at 3.5 d after ABI.The gene expression profiles demonstrated that ABI up-regulated DNA damage repair pathways and down-regulated cell adhesion molecules,focal adhesion and IgA production pathways.Conclusions The p53 signaling pathway and some key genes such as Lck,Cdkl,and Fyn may contribute to the radiation-induced intestinal injury.

Effect of Olaparib on proliferation activity and radiosensitization of human non-small cell lung cancer cells / 国际生物医学工程杂志

Objective To investigate the effects of Olaparib on cell proliferation and radiosensitization of human non-small cell lung cancer cells.Methods Non-small cell lung H460 and H1299 cell lines were cultured in vitro and the cells in logarithmic growth phase were selected for experiments.MTT and colony formation assays were used to determine cell proliferation and radiosensitization,respectively.Single cell gel electrophoresis assay (comet assay) was used to detect irradiation-induced DNA damage.Results The results of MTT assay showed that Olaparib inhibited the proliferation of H460 and H1299 cells in a dose-dependent pattern (all P＜0.05).H1299 cell line was more sensitive to Olaparib than H460 cells.The results of colony formation assay showed that Olaparib enhanced the radiosensitizition of H460 and H1299 cells (all P＜0.05).The results of comet assay showed that Olaparib increased γ ray-induced DNA damage.Conclusions Olapani can enhance the radiosensitization of human non-small cell lung cancer cells,and the radiosensitization effect of Olaparib may be associated with the inhibition of cell proliferation and induction of irradiation-induced DNA damage.

Mesenchymal stem cells transplantation promote the structural repairation of mice intestinal injury induced by radiation / 重庆医学

Objective To study the effect of human umbilical cord mesenchymal stem cells (hMSCs) on the survival rate of mice with radiation-induced intestinal injury and its effect on the repair of intestinal damage.Methods Adult C57BL/6J mice were selected and divided into control group and abdomen irradiation + PBS(IR + PBS) group and abdominal irradiation+hMSCs transplantation treatment (IR+hMSCs)group.Intestinal injury model was induced by abdominal irradiation at 13 Gy of T ray and the 30-day survival rate was recorded.On the 3.5th and 5.0th day after irradiation,HE staining was used to observe changes in the villus structure and thc number of intestinal crypts in each segment of the small intestine (duodenum,jejunum,and ileum).Results The survival rate of IR+hMSCs group was significantly higher than that of IR+PBS group (P＜0.05).On the 3.5th day after 13 Gy of abdomen irradiation,the duodenum,cavities and ileum villus in IR+PBS group were all fractured,the length was shortened,and the numbers were sparse when compared with the control group,while the hMSCs reduced the intestinal damage.On the 5.0th day after irradiation,the structural integrity of the small intestine in IR+PBS group was repaired slightly,but it still more serious than that of IR+hMSCs group (P＜0.01).The amount of intestine crypts were significantly higher in IR+hMSCs group than that of IR+PBS group,but were significantly lower than that of control group (P＜0.01) at 3.5th day and 5.0th day after radiation.Conclusion Transplantation of hMSCs can improve the survival rate and promote the repairation of intestinal injury induced by radiation in mice.MSCs are hopeful to be used on the treatment of radiation-induced intestinal injury.

Research progress on the functional regulation of Nrf2 gene and its mechanisms in lung cancer / 国际生物医学工程杂志

As a nuclear transcription factor , nuclear factor E2-related factor 2 (Nrf2) protein plays an important role in regulating intracellular redox balance and cellular resistance to various stresses. Oxidative stress and ionization stress can cause Nrf2 to translocate from cytoplasm to nucleus. Then the Nrf2 binds to antioxidant response elements to regulate the transcription of antioxidant genes such as NQO1 and HO-1 and play the anti-oxidant protective effect. In recent years, the results show that many cancer cells, including lung cancer, involve Nrf2 overexpression, and there is a connection between Nrf2 protein levels and the occurrence, development, chemoradiotherapy resistance as well as the patient prognosis of lung cancer. The excessive Nrf2 protein levels in lung cancer cells, caused by the mutation of Nrf2 or its inhibitory protein Keap1, can promote the proliferation and migration of lung cancer cells, leading to chemoradiotherapy resistance and poor prognosis. The structure, function and regulation of Nrf2 were summarized, and the research progress on the mechanism of Nrf2 in the occurrence, development and treatment of lung cancer were reviewed.

Lethal effect of RI-1 on MSH2-deficient colorectal cancer cells / 基础医学与临床

Objective To explore the lethal action and possible mechanism of RI-1, a RAD51 inhibitor, on MSH2 deficient colorectal cancer cells.Methods The expression of MSH2 protein level was assessed by Western blot, and the sensibility of human colorectal cancer cells to RI-1 (10, 20, 30, 40 and 50 μmol/L)was measured by MTT method.Lentivirus vectors MSH2-shRNA and Neg-shRNA (negative control) were constructed and transfected into HT29 cell.Apoptosis and DNA damage of cells treated with RI-1(40 μmol/L)were detected by flow cytometry and Single cell gel electrophoresis respectively.In addition, the formation of γ-H2AX foci was analyzed by immunofluorescence.Results Compared with control, MSH2-deficient HCT8 cells had obviously apoptosis(P<0.01);in HCT8 and HT29 Shmsh2 cells, tail DNA%, tail length, tail moment and olive tail moment were markedly increased(P<0.05),and the number of γ-H2AX focus were increased(P<0.01).Conclusions RAD51 inhibitor RI-1 selectively kills MSH2 deficient colorectal cancer cells by increasing DNA damage.

Inhibitory effect of Rb94 gene combined with radiotherapy on growth of esophageal carcinoma cells of tumor-bearing nude mice / 吉林大学学报(医学版)

Objective:To study the inhibitory effect of retinoblastoma 94(Rb94) gene combined with radiotherapy ionizing radiation on the growth of esophageal carcinoma cells of tumor-bearing nude mice, and to clarify the synergistic effect of Rb94 gene and radiotherapy in inhibiting the growth of tumor cells.Methods:The models of tumor-bearing BALB/c-nu nude mice were built by inoculating the K150 cells.The model mice were divided into five groups:blank control(no any treatment), Ad-LacZ(control adenovirus including LacZ gene but not Rb94 gene, Ad-LacZ was transfered into tumor xenograft on 0, 3, 7 d separately), Ad-Rb94(tumor xenograft was transfected with Ad-Rb94 on 0, 3, 7 d separately), radiation (tumor xenograft was irradiated with 4 Gy γ-radiation on 1, 4, 8 d separately) and Ad-Rb94 combined with radiation(combination group, tumor xenograft was irradiated with 4 Gy γ-radiation after transfected with Ad-Rb94) groups.The volumes and the weights of esophageal carcinoma and the inhibitory rates of tumor growth of the mice in various groups were detected.The expression levels of ABL and JNK kinase in tumor tissue of the mice in various groups were measured,and the pathological changes of tumor tissue were investigated.Results:The speeds of tumor growth of the nude mice in Ad-RB94, radiation, and combination groups were slower than that in control group.The volume of esophageal carcinoma in combination group at day 15 after treatment was markedly smaller than those in Ad-RB94 and radiation groups,and there were significant differences compared with control group and Ad-LacZ group (F=26.7,23.8;P<0.01).The tumor weight of the nude mice in combination group was the lightest at the end of treatment;the inhibitory rate of tumor growth in combination group reached 81.16% and was significantly higher than those in Ad-Rb94 group(57.84%)and radiation group(38.20%)(P<0.01).The expression levels of ALB and JNK kinase in tumor tissue of the mice in combination group was markedly higher than those in control group(P<0.01).Compared with other groups, the tumor cells in combination group had fewer karyokinesis and lower level of nuclei hyperchromasia.Conclusion:Rb94 gene combined with radiotherapy shows synergistic effect in inhibiting the growth of tumor of tumor-bearing nude mice.

Research progress in molecular mechanism of hematopoietic stem cell injury induced by ionizing radiation / 基础医学与临床

Hematopoietic stem cell ( HSCs) injury induced by ionizing radiation ( IR) is the primary cause of death after exposure to ionizing radiation .The mechanisms of inducing HSCs damage include induction of HSCs apoptosis via the P53-Puma pathway;promotion of HSCs differentiation via the activation of the G-CSF/Stat3/BATF-depend-ent differentiation checkpoint;induction of HSCs senescence via the ROS-P38 pathway; and damage to the HSCs niche.Recent researches provide a basis for the prevention and treatment of bone marrow suppression caused by ionizing radiation .

Effect and mechanism of neuroepithelial cell transforming gene 1 on cellular radiosensitivity / 中华放射医学与防护杂志

Objective To study the effect of neuroepithelial cell transforming gene 1 (Net1) on the cellular radiosensitivity and underlying mechanism.Methods Real-time quantitative PCR was used to measure the variations in Net1 expression level upon irradiation.Radiosensitivity was analyzed by colonyforming assay after Net1-siRNAs.Net1-associated proteins were identified by co-immunoprecipitation.Results The Net1 mRNA level in the cells was increased significantly (t =-10.52,P ＜ 0.05) after irradiation.Compared to the control group,siRNA-mediated silencing of Net1 enhanced cell radiosensitivity (t =15.31,11.65,P ＜0.05).Net1 was found to interact with Ku70,Ku80 and DNA-PKcs under either normal conditions or after irradiation.Conclusions Net1 could protect cells from irradiation by interaction with DNA repair proteins in non-homologous end joining pathway.

The Effect of XRCC2 Gene Silencing Combined with Radiation on Human Colonic Transplanted Carcinoma in Nude Mice / 中国医科大学学报

Objective To study the curative effect of XRCC2 gene silencing mediated by shRNA combined with radiation on human colonic trans?planted carcinoma in nude mice. Methods Colonic carcinoma T84 cells were transfered into BALB/c nude mice to establish a tumor xenograft mod?el in vivo. Mice were divided into three groups:control,shRNA?SC and shRNA?XRCC2 and exposed to X?ray radiation. The change of volume and weight of the xenografts were examined after receiving radiotherapy and the pathological analysis of tumor tissues were conducted. Results Tumor xenografts transfected with shRNA?XRCC2 in nude mice grew slowly. The xenograft volume in the shRNA?XRCC2 group was decreased significant?ly from day 12 to day 28 after radiotherapy compared with the control group(P<0.01). The xenograft weight in the shRNA?XRCC2 group was small?er than in the control group,with statistically significant difference(t=18.843,P<0.01). The inhibited rate of xenografts in the shRNA?XRCC2 group(56.25%),was markedly higher than that in the shRNA?SC group(4.69%). Pathological analysis of colonic transplanted carcinoma showed that nuclear atypia was not obvious,karyokinesis was decreased and small areas of necrosis were present in tumor xenografts treated with shRNA?XRCC2 transfection. Conclusion XRCC2 gene silencing combined with radiation has significant inhibition effect on colonic transplanted carcino?ma in nude mice.

Inhibitory effect of resveratrol on expression of IL-1β in mesenchymal stem cells exposed to radiation / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the inhibitory effect of resveratrol on interleukin-1β (IL-1β) production in mesenchymal stem cells (MSCs) exposed to radiation and the action mechanism of resveratrol.</p><p><b>METHODS</b>MSCs were divided into blank control group, radiation group, shRNA interference group, and resveratrol groups. The resveratrol groups were given different doses of resveratrol (50, 100, and 200 µmol/L) before radiation. The secretion and expression of IL-1β was measured by enzyme-linked immunosorbent assay, Western blot, and RT-PCR.</p><p><b>RESULTS</b>Compared with the radiation group, the resveratrol groups had significantly decreased extracellular secretion of IL-1β (t = 83.34, 24.48, and 12.52, P < 0.05 for all) and significantly decreased intracellular expression of IL-1β protein and mRNA (t = 8.695, 14.77, and 13.9, P < 0.05 for all). Compared with those given 200 µmol/L resveratrol alone before radiation, the MSCs treated by SIRT1 silencing and given 200 µmol/L resveratrol before radiation had significantly increased extracellular secretion of IL-1β (t = 18.57, P < 0.05) and significantly increased intracellular expression of IL-1β protein and mRNA (t = 10.24, P < 0.05).</p><p><b>CONCLUSION</b>Resveratrol can significantly inhibit the production of IL-1β in MSCs exposed to radiation, and SIRT1 may play a key regulatory role in the process of inflammation induced by radiation.</p>