AIM： To perform a systematic meta-analysis to in- vestigate the association between X-ray repair crosscomplementing group 1 （XRCC1） polymorphisms and hepatocellular carcinoma （HCC） risk. METHODS： Relevant studie...AIM： To perform a systematic meta-analysis to in- vestigate the association between X-ray repair crosscomplementing group 1 （XRCC1） polymorphisms and hepatocellular carcinoma （HCC） risk. METHODS： Relevant studies extracted from PubMed, Embase, Wanfang, VIP and the Chinese National Knowledge Infrastructure databases up to March 2012 were included in the study. Stata software, version 11.0, was used for the statistical analysis. The odds ratios （ORs） and 95% confidence interval （CI） of the XRCC1 polymorphisms in HCC patients were analyzed and compared with healthy controls. The meta-analysis was performed using fixed-effect or random-effect methods, depending on the absence or presence of significant heterogeneity. RESULTS： Eleven studies with 2075 HCC cases and 2604 controls met our eligibility criteria （four studies, 888 cases and 938 controls for Arg194Trp, four studies, 858 cases and 880 controls for Arg280His, and nine studies, 1845 cases and 2401 controls for Arg399Gln）. The meta-analysis revealed no associations between the Arg194Trp and Arg399GIn polymorphisms of the XRCC1 gene and HCC risk under all contrast models （codominant, dominant and recessive models） in the overall analysis and sensitivity analysis （the studies with controls not in the Hardy-Weinberg equilibrium were excluded）. For XRCC1 Arg280His polymorphism, the overall analysis revealed the significant associa- tion between the His/His genotype and the increased risk of HCC （His/His vs Arg/Arg model, OR： 1.96, 95% CI： 1.03-3.75, P = 0.04）. However, sensitivity analysis showed an altered pattern of result and non-significant association （OR： 2.06, 95% CI： 0.67-6.25, P = 0.20）. The heterogeneity hypothesis test did not reveal any heterogeneity, and Begg＇s and Egger＇s tests did not find any obvious publication bias. CONCLUSION： The XRCC1 Arg194Trp and Arg399GIn polymorphisms are not associated with HCC risk. More rigorous association studies are needed to verify the involvement ofXRCC1 Arg280His polymorphism in HCC susceptibility.展开更多
OBJECTIVE： To evaluate the association of X-ray cross-complementing group 1 （XRCC1） Arg399GIn, Arg194Trp and Arg280His polymorphisms with the risk of glioma. DATA SOURCES： A systematic literature search of papers ...OBJECTIVE： To evaluate the association of X-ray cross-complementing group 1 （XRCC1） Arg399GIn, Arg194Trp and Arg280His polymorphisms with the risk of glioma. DATA SOURCES： A systematic literature search of papers published from January 2000 to August 2012 in PubMed, Embase, China National Knowledge Infrastructure database, and Wanfang da- tabase was performed. The key words used were ＂glioma＂, ＂polymorphism＂, and ＂XRCC1 or X-ray repair cross-complementing group 1＂. References cited in the retrieved articles were screened manually to identify additional eligible studies. STUDY SELECTION： Studies were identified according to the following inclusion criteria： case-control design was based on unrelated individuals; and genotype frequency was available to estimate an odds ratio （OR） and 95% confidence interval （CI）. Meta-analysis was performed for the selected studies after strict screening. Dominant and recessive genetic models were used and the relationship between homozygous mutant genotype frequencies and mutant gene frequency and glioma incidence was investigated. We chose the fixed or random effect model according to the heterogeneity to calculate OR and 95%CI, and sensitivity analyses were conducted. Publication bias was examined using the inverted funnel plot and the Egger＇s test using Stata 12.0 software. MAIN OUTCOME MEASURES： Association of XRCC1 Arg399GIn, Arg194Trp, and Arg280His polymorphisms with the risk of glioma, and subgroup analyses were performed according to differ- ent ethnicities of the subjects.RESULTS： Twelve articles were included in the meta-analysis. Eleven of the articles were concerned with the Arg399GIn polymorphism and glioma onset risk. Significantly increased glioma risks were found only in the dominant model （Gin/Gin ＋ GIn/Arg versus Arg/Arg： OR = 1.26, 95%CI= 1.03-1.54, P = 0.02）. In the subgroup analysis by ethnicity, significantly increased risk was found in Asian subjects in the recessive （OR = 1.46, 95%CI= 1.04-2.45, P = 0.03） and dominant models （OR = 1.40, 95%CI= 1.10-1.78, P = 0.007）, and homozygote contrast （OR = 1.69, 95%CI= 1.17-2.45, P = 0.005）, but not in Caucasian sub- jects. For association of the Arg194Trp （eight studies） and Arg280His （four studies） polymorphisms with glioma risk, the meta-analysis did not reveal a significant effect in the allele contrast, the recessive genetic model, the dominant genetic model, or homozygote contrast. CONCLUSION： The XRCC1 Arg399GIn polymorphism may be a biomarker of glioma susceptibility, espe- cially in Asian populations. The Arg194Trp and Arg280His polymorphisms were not associated with overall glioma risk.展开更多
Recent studies have shown that tea polyphenols can cross the blood-brain barrier, inhibit apoptosis and play a neuroprotective role against cerebral ischemia. Furthermore, tea polyphenols can decrease DNA damage cause...Recent studies have shown that tea polyphenols can cross the blood-brain barrier, inhibit apoptosis and play a neuroprotective role against cerebral ischemia. Furthermore, tea polyphenols can decrease DNA damage caused by free radicals. We hypothesized that tea polyphenols repair DNA damage and inhibit neuronal apoptosis during global cerebral ischemia/reperfusion. To test this hypothesis, we employed a rat model of global cerebral ischemia/reperfusion. We demonstrated that intraperitoneal injection of tea polyphenols immediately after reperfusion significantly reduced apoptosis in the hippocampal CA1 region; this effect started 6 hours following reperfusion. Immunohistochemical staining showed that tea polyphenols could reverse the ischemia/reperfusion-induced reduction in the expression of DNA repair proteins, X-ray repair cross-complementing protein 1 and apudnic/apyrimidinic endonuclease/redox factor-1 starting at 2 hours. Both effects lasted at least 72 hours. These experimental findings suggest that tea polyphenols promote DNA damage repair and protect against apoptosis in the brain.展开更多
AIM: To investigate the molecular mechanisms underlying the reversal effect of emodin on platinum resistance in hepatocellular carcinoma. METHODS: After the addition of 10 μmol/L emodin to HepG2/oxaliplatin (OXA) cel...AIM: To investigate the molecular mechanisms underlying the reversal effect of emodin on platinum resistance in hepatocellular carcinoma. METHODS: After the addition of 10 μmol/L emodin to HepG2/oxaliplatin (OXA) cells, the inhibition rate (IR), 50% inhibitory concentration (IC 50 ) and reversal index (IC 50 in experimental group/IC 50 in control group) were calculated. For HepG2, HepG2/OXA, HepG2/OXA/T, each cell line was divided into a control group, OXA group, OXA + fibroblast growth factor 7 (FGF7) group and OXA + emodin group, and the final concentrations of FGF7, emodin and OXA in each group were 5 ng/mL, 10 μg/mL and 10 μmol/L, respectively. Single-cell gel electrophoresis was conducted to detect DNA damage, and the fibroblast growth factor receptor 2 (FGFR2), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) and excision repair cross-complementing gene 1 (ERCC1) protein expression levels in each group were examined by Western blotting. RESULTS: Compared with the IC50 of 120.78 μmol/L in HepG2/OXA cells, the IC 50 decreased to 39.65 μmol/L after treatment with 10 μmol/L emodin; thus, the reversal index was 3.05. Compared with the control group, the tail length and Olive tail length in the OXA group, OXA + FGF7 group and OXA + emodin group were significantly increased, and the differences were statistically significant (P < 0.01). The tail length and Olive tail length were lower in the OXA + FGF7 group than in the OXA group, and this difference was also statistically significant. Compared with the OXA + FGF7 group, the tail extent, the Olive tail moment and the percentage of tail DNA were significantly increased in the OXA + emodin group, and these differences were statistically significant (P < 0.01). In comparison with its parental cell line HepG2, the HepG2/OXA cells demonstrated significantly increased FGFR2, p-ERK1/2 and ERCC1 expression levels, whereas the expression of all three molecules was significantly inhibited in HepG2/ OXA/T cells, in which FGFR2 was silenced by FGFR2 shRNA. In the examined HepG2 cells, the FGFR2, p-ERK1/2 and ERCC1 expression levels demonstrated increasing trends in the OXA group and OXA + FGF7 group. Compared with the OXA group and OXA + FGF7 group, the FGFR2, p-ERK1/2, and ERCC1 expression levels were significantly lower in the OXA + emodin group, and these differences were statistically significant. In the HepG2/OXA/T cell line that was transfected with FGFR2 shRNA, the FGFR2, p-ERK1/2 and ERCC1 expression levels were significantly inhibited, but there were no significant differences in these expression levels among the OXA, OXA + FGF7 and OXA + emodin groups. CONCLUSION: Emodin markedly reversed OXA resistance by enhancing OXA DNA damage in HepG2/OXA cells, and the molecular mechanism was related to the inhibitory effect on ERCC1 expression being mediated by the FGFR2/ERK1/2 signaling pathway.展开更多
AIM To investigate the interactions of the DNA repair gene excision repair cross complementing group 5(ERCC5) and the metabolic gene glutathione S-transferase pi 1(GSTP1) and their effects on atrophic gastritis(AG) an...AIM To investigate the interactions of the DNA repair gene excision repair cross complementing group 5(ERCC5) and the metabolic gene glutathione S-transferase pi 1(GSTP1) and their effects on atrophic gastritis(AG) and gastric cancer(GC) risk.METHODS Seven ERCC5 single nucleotide polymorphisms(SNPs)(rs1047768, rs2094258, rs2228959, rs4150291, rs4150383, rs751402, and rs873601) and GSTP1 SNP rs1695 were detected using the Sequenom MassA RRAY platform in 450 GC patients, 634 AG cases, and 621 healthy control subjects in a Chinese population.RESULTS Two pairwise combinations(ERCC5 rs2094258 and rs873601 with GSTP1 rs1695) influenced AG risk(P_(interaction) = 0.008 and 0.043, respectively), and the ERCC5 rs2094258-GSTP1 rs1695 SNP pair demonstrated an antagonistic effect, while ERCC5 rs873601-GSTP1 rs1695 showed a synergistic effect on AG risk OR = 0.51 and 1.79, respectively). No pairwise combinations were observed in relation to GC risk. There were no cumulative effects among the pairwise interactions(ERCC5 rs2094258 and rs873601 with GSTP1 rs1695) on AG susceptibility(P_(trend) > 0.05). When the modification effect of Helicobacter pylori(H. pylori) infection was evaluated, the cumulative effect of one of the aforementioned pairwise interactions(ERCC5 rs873601-GSTP1 rs1695) was associated with an increased AG risk in the case of negative H. pylori status(P_(trend)= 0.043).CONCLUSION There is a multifarious interaction between the DNA repair gene ERCC5 SNPs(rs2094258 and rs873601) and the metabolic gene GSTP1 rs1695, which may form the basis for various inter-individual susceptibilities to AG.展开更多
Objective： To estimate the relationship between genetic polymorphisms of X-ray repair cross- complementing group 1 （XRCC1） and the susceptibility to childhood acute lymphoblastic leukemia （ALL）. Methods： Relevan...Objective： To estimate the relationship between genetic polymorphisms of X-ray repair cross- complementing group 1 （XRCC1） and the susceptibility to childhood acute lymphoblastic leukemia （ALL）. Methods： Relevant case-control studies were enrolled in the meta-analysis. We applied Rev Man 4.2 software to pool raw data and test studies＇ heterogeneity and to calculate the incorporated odds ratio （OR） and 95% confidence interval （95% CI）. Results： Our data showed that the OR for the Gln allele of the Arg399Gln polymorphism, compared with the Arg allele, was 1.35 （95% CI, 1.16-1.57; P〈0.0001） for childhood ALL patients. Similarly, the homozygous genotype Gln/Gln and heterozygous genotype Arg/Gln both significantly increased the risk of childhood ALL compared with the wild genotype Arg/Arg （OR =1.58; 95% CI, 1.13-2.21; P=0.008; OR =1.51; 95% CI, 1.21-1.87; P=0.0002）. The dominant model of Arg399Gln was associated with childhood ALL risk （OR =1.54; 95% CI, 1.25-1.89; P〈0.0001）. The ethnic subgroup analysis demonstrated that the Gln allele in all five ethnic groups was prone to be a risk factor for childhood ALL just with different degrees of correlation while Arg194Trp SNP showed a protective or risk factor or irrelevant thing in different races. Conclusions： XRCC1 399 polymorphism may increase the risk of childhood ALL. Different ethnic groups with some gene polymorphism have different disease risks.展开更多
BACKGROUND： Recent studies have shown that the selective inhibitor of c-Jun N-terminal kinases （JNKs） signaling pathway, SP600125, exhibits neuronal protective effects in a rat model of brain ischemia/reperfusion. ...BACKGROUND： Recent studies have shown that the selective inhibitor of c-Jun N-terminal kinases （JNKs） signaling pathway, SP600125, exhibits neuronal protective effects in a rat model of brain ischemia/reperfusion. OBJECTIVE： To determine the mechanisms of neuroprotective effects of SP600125 in a rat model of brain ischemia/reperfusion, and determine the role of the JNK signaling pathway in SP600125-induced effects. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Animal Experiment Center, Medical School of Xi＇an Jiaotong University from June 2007 to September 2008. MATERIALS： SP600125 was provided by Biosource, USA; rabbit anti-phospho-JNK （Thr183/Tyr185） polyclonal antibody from Cell Signaling Technology, USA; rabbit anti-X-ray repair cross-complementing protein 1 （XRCC1） and anti-Ku70 polyclonal antibodies from Santa Cruz Biotechnology, USA; and TUNEL kit from Beijing Huamei Biology, China. METHODS： A total of 108 male, 4-month-old, Sprague Dawley rats were randomly assigned to three groups, with 36 rats per group. The sham operation group and ischemia/reperfusion group （I/R group） were intracerebroventricularly injected with 10 μL 1% DMSO. The SP600125-treated group （pre-SP group） was given 10 μL SP600125 （3 μg/μL）. Thirty minutes later, brain ischemia was induced in the I/R and pre-SP groups using the four-vessel occlusion method. Specifically, whole brain ischemia was induced for 6 minutes, and the clips were released to restore carotid artery blood flow. Rats from each group were observed at 2, 6, 12, 24, 48, and 72 hours, with 6 rats for each time point. The sham operation group was treated with the same surgical exposure procedures, with exception of occlusion of the carotid artery. MAIN OUTCOME MEASURES： Hematoxylin-eosin staining was used to observe neuronal survival in the hippocampal CA1 region, TUNEL was used to detect apoptosis in the hippocampal CA1 region, and immunohistochemistry was used to detect expression of phospho-JNK, XRCC1, and Ku70. RESULTS： Following brain ischemia/reperfusion, neuronal survival significantly decreased, and the number of apoptotic cells significantly increased （P 〈 0.01）. Compared with the I/R group, neuronal survival significantly increased in the pre-SP group, and the number of apoptotic cells significantly decreased （P 〈 0.01）. Expression of phospho-JNK increased, and XRCC1 and Ku70 significantly decreased （P 〈 0.05） following ischemia/reperfusion. Compared with the I/R group, expression of phospho-JNK decreased, and XRCC1 and Ku70 significantly increased in the pre-SP group （P 〈 0.05）. Correlation analysis revealed an inverse correlation between phospho-JNK gray value and XRCC1 and Ku70 gray values in the hippocampal CA1 region （r = -0.983, -0.953, P 〈 0.01）. CONCLUSION： SP600125 treatment decreased apoptosis induced by global brain ischemia/reperfusion in the rat hippocampal CA1 region. Results suggested that the neuroprotective effects were due to inhibited phosphorylation of JNK and reduced down-regulation of XRCC1 and Ku70.展开更多
Background Several studies have evaluated the association between polymorphisms of encoding excision repair cross complementation group 1 （ERCC1） enzyme and lung cancer risk in diverse populations but with conflicti...Background Several studies have evaluated the association between polymorphisms of encoding excision repair cross complementation group 1 （ERCC1） enzyme and lung cancer risk in diverse populations but with conflicting results.By pooling the relatively small samples in each study, it is possible to perform a meta-analysis of the evidence by rigorous methods.Methods Embase, Ovid, Medline and Chinese National Knowledge Infrastructure were searched. Additional studies were identified from references in original studies or review articles. Articles meeting the inclusion criteria were reviewed systematically, and the reported data were aggregated using the statistical techniques of meta-analysis.Results We found 3810 cases with lung cancer and 4332 controls from seven eligible studies. T19007C polymorphism showed no significant effect on lung cancer risk （C allele vs. T allele： odds ratio （OR）=0.91, 95% confidence interval （CI）=0.80-1.04; CC vs. TT： OR=0.76, 95% CI=0.56-1.02; CC vs. （CT＋TT）： OR=0.96, 95% CI=-0.84-1.10）. Similarly,there was no significant main effects for T19007C polymorphism on lung cancer risk when stratified analyses by ethnicity （Chinese or Caucasian）. No significant association was found between C8092A polymorphism （3060 patients and 2729 controls） and the risk of lung cancer （A allele vs. C allele： OR=1.03, 95% CI=0.95-1.11; AA vs. CC： OR=1.08, 95% CI=-0.88-1.33; AA vs. （AC＋CC）： OR=1.08, 95% CI=-0.88-1.31）.Conclusion We found little evidence of an association between the T1900C or C8092A polymorphisms of ERCC 1 and the risk of lung cancer in Caucasian or Han Chinese people.展开更多
Background：Conflicting results about the association between expression level of excision repair cross-complementation group 1 （ERCC1） and clinical outcome in patients with colorectal cancer （CRC） receiving chemo...Background：Conflicting results about the association between expression level of excision repair cross-complementation group 1 （ERCC1） and clinical outcome in patients with colorectal cancer （CRC） receiving chemotherapy have been reported.Thus,we searched the available articles and performed the meta-analysis to elucidate the prognostic role of ERCC1 expression in patients with CRC.Methods：A thorough literature search using PubMed （Medline）,Embase,Cochrane Library,Web of Science databases,and Chinese Science Citation Database was conducted to obtain the relevant studies.Pooled hazard ratios （HRs） or odds ratios （ORs） with 95% confidence intervals （CIs） were calculated to estimate the results.Results：A total of 11 studies were finally enrolled in this meta-analysis.Compared with patients with lower ERCC1 expression,patients with higher ERCC1 expression tended to have unfavorable overall survival （OS） （HR =2.325,95% CI：1.720-3.143,P 〈 0.001）,progression-free survival （PFS） （HR =1.917,95% CI：1.366-2.691,P 〈 0.001） and poor response to chemotherapy （OR =0.491,95% CI：0.243-0.990,P =0.047）.Subgroup analyses by treatment setting,ethnicity,HR extraction,detection methods,survival analysis,and study design demonstrated that our results were robust.Conclusions：ERCC1 expression may be taken as an effective prognostic factor predicting the response to chemotherapy,OS,and PFS.Further studies with better study design and longer follow-up are warranted in order to gain a deeper understanding of ERCC 1＇s prognostic value.展开更多
基金Supported by International Science and Technology Cooperation Program of the Ministry of Science and Technology,No.010S2012ZR0058the National Basic Research Program of China,No. 2012CB526706+2 种基金the Innovation Program of Shanghai Municipal Education Commission,No.13ZZ060the Fund of Shanghai Municipal Health Bureau,No. 2008Y077the Special Program for Military Medicine,No. 2010JS15
文摘AIM： To perform a systematic meta-analysis to in- vestigate the association between X-ray repair crosscomplementing group 1 （XRCC1） polymorphisms and hepatocellular carcinoma （HCC） risk. METHODS： Relevant studies extracted from PubMed, Embase, Wanfang, VIP and the Chinese National Knowledge Infrastructure databases up to March 2012 were included in the study. Stata software, version 11.0, was used for the statistical analysis. The odds ratios （ORs） and 95% confidence interval （CI） of the XRCC1 polymorphisms in HCC patients were analyzed and compared with healthy controls. The meta-analysis was performed using fixed-effect or random-effect methods, depending on the absence or presence of significant heterogeneity. RESULTS： Eleven studies with 2075 HCC cases and 2604 controls met our eligibility criteria （four studies, 888 cases and 938 controls for Arg194Trp, four studies, 858 cases and 880 controls for Arg280His, and nine studies, 1845 cases and 2401 controls for Arg399Gln）. The meta-analysis revealed no associations between the Arg194Trp and Arg399GIn polymorphisms of the XRCC1 gene and HCC risk under all contrast models （codominant, dominant and recessive models） in the overall analysis and sensitivity analysis （the studies with controls not in the Hardy-Weinberg equilibrium were excluded）. For XRCC1 Arg280His polymorphism, the overall analysis revealed the significant associa- tion between the His/His genotype and the increased risk of HCC （His/His vs Arg/Arg model, OR： 1.96, 95% CI： 1.03-3.75, P = 0.04）. However, sensitivity analysis showed an altered pattern of result and non-significant association （OR： 2.06, 95% CI： 0.67-6.25, P = 0.20）. The heterogeneity hypothesis test did not reveal any heterogeneity, and Begg＇s and Egger＇s tests did not find any obvious publication bias. CONCLUSION： The XRCC1 Arg194Trp and Arg399GIn polymorphisms are not associated with HCC risk. More rigorous association studies are needed to verify the involvement ofXRCC1 Arg280His polymorphism in HCC susceptibility.
基金The Fundamental Research Funds for Jilin University in China,No.450060445246the High-Tech Industrial Development Project of Jilin Province in China,No.20090633+1 种基金the Scientific Research Foundation of Jilin Province in China,No.20130206001YY,20120713 and 200905169the Scientific Research Foundation of Changchun in China,No.12SF29
文摘OBJECTIVE： To evaluate the association of X-ray cross-complementing group 1 （XRCC1） Arg399GIn, Arg194Trp and Arg280His polymorphisms with the risk of glioma. DATA SOURCES： A systematic literature search of papers published from January 2000 to August 2012 in PubMed, Embase, China National Knowledge Infrastructure database, and Wanfang da- tabase was performed. The key words used were ＂glioma＂, ＂polymorphism＂, and ＂XRCC1 or X-ray repair cross-complementing group 1＂. References cited in the retrieved articles were screened manually to identify additional eligible studies. STUDY SELECTION： Studies were identified according to the following inclusion criteria： case-control design was based on unrelated individuals; and genotype frequency was available to estimate an odds ratio （OR） and 95% confidence interval （CI）. Meta-analysis was performed for the selected studies after strict screening. Dominant and recessive genetic models were used and the relationship between homozygous mutant genotype frequencies and mutant gene frequency and glioma incidence was investigated. We chose the fixed or random effect model according to the heterogeneity to calculate OR and 95%CI, and sensitivity analyses were conducted. Publication bias was examined using the inverted funnel plot and the Egger＇s test using Stata 12.0 software. MAIN OUTCOME MEASURES： Association of XRCC1 Arg399GIn, Arg194Trp, and Arg280His polymorphisms with the risk of glioma, and subgroup analyses were performed according to differ- ent ethnicities of the subjects.RESULTS： Twelve articles were included in the meta-analysis. Eleven of the articles were concerned with the Arg399GIn polymorphism and glioma onset risk. Significantly increased glioma risks were found only in the dominant model （Gin/Gin ＋ GIn/Arg versus Arg/Arg： OR = 1.26, 95%CI= 1.03-1.54, P = 0.02）. In the subgroup analysis by ethnicity, significantly increased risk was found in Asian subjects in the recessive （OR = 1.46, 95%CI= 1.04-2.45, P = 0.03） and dominant models （OR = 1.40, 95%CI= 1.10-1.78, P = 0.007）, and homozygote contrast （OR = 1.69, 95%CI= 1.17-2.45, P = 0.005）, but not in Caucasian sub- jects. For association of the Arg194Trp （eight studies） and Arg280His （four studies） polymorphisms with glioma risk, the meta-analysis did not reveal a significant effect in the allele contrast, the recessive genetic model, the dominant genetic model, or homozygote contrast. CONCLUSION： The XRCC1 Arg399GIn polymorphism may be a biomarker of glioma susceptibility, espe- cially in Asian populations. The Arg194Trp and Arg280His polymorphisms were not associated with overall glioma risk.
基金supported by the National Natural Science Foundation of China, No. 30571790
文摘Recent studies have shown that tea polyphenols can cross the blood-brain barrier, inhibit apoptosis and play a neuroprotective role against cerebral ischemia. Furthermore, tea polyphenols can decrease DNA damage caused by free radicals. We hypothesized that tea polyphenols repair DNA damage and inhibit neuronal apoptosis during global cerebral ischemia/reperfusion. To test this hypothesis, we employed a rat model of global cerebral ischemia/reperfusion. We demonstrated that intraperitoneal injection of tea polyphenols immediately after reperfusion significantly reduced apoptosis in the hippocampal CA1 region; this effect started 6 hours following reperfusion. Immunohistochemical staining showed that tea polyphenols could reverse the ischemia/reperfusion-induced reduction in the expression of DNA repair proteins, X-ray repair cross-complementing protein 1 and apudnic/apyrimidinic endonuclease/redox factor-1 starting at 2 hours. Both effects lasted at least 72 hours. These experimental findings suggest that tea polyphenols promote DNA damage repair and protect against apoptosis in the brain.
基金Supported by National Natural Sciences Foundation of China,No. 81001067the Ministry of Science and Technology International Cooperation Project, No. 2010DFA31870the AstraZeneca Special Research Foundation for Targeted Therapy of the Wu Jieping Medical Foundation, No. 320.6700.09068
文摘AIM: To investigate the molecular mechanisms underlying the reversal effect of emodin on platinum resistance in hepatocellular carcinoma. METHODS: After the addition of 10 μmol/L emodin to HepG2/oxaliplatin (OXA) cells, the inhibition rate (IR), 50% inhibitory concentration (IC 50 ) and reversal index (IC 50 in experimental group/IC 50 in control group) were calculated. For HepG2, HepG2/OXA, HepG2/OXA/T, each cell line was divided into a control group, OXA group, OXA + fibroblast growth factor 7 (FGF7) group and OXA + emodin group, and the final concentrations of FGF7, emodin and OXA in each group were 5 ng/mL, 10 μg/mL and 10 μmol/L, respectively. Single-cell gel electrophoresis was conducted to detect DNA damage, and the fibroblast growth factor receptor 2 (FGFR2), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) and excision repair cross-complementing gene 1 (ERCC1) protein expression levels in each group were examined by Western blotting. RESULTS: Compared with the IC50 of 120.78 μmol/L in HepG2/OXA cells, the IC 50 decreased to 39.65 μmol/L after treatment with 10 μmol/L emodin; thus, the reversal index was 3.05. Compared with the control group, the tail length and Olive tail length in the OXA group, OXA + FGF7 group and OXA + emodin group were significantly increased, and the differences were statistically significant (P < 0.01). The tail length and Olive tail length were lower in the OXA + FGF7 group than in the OXA group, and this difference was also statistically significant. Compared with the OXA + FGF7 group, the tail extent, the Olive tail moment and the percentage of tail DNA were significantly increased in the OXA + emodin group, and these differences were statistically significant (P < 0.01). In comparison with its parental cell line HepG2, the HepG2/OXA cells demonstrated significantly increased FGFR2, p-ERK1/2 and ERCC1 expression levels, whereas the expression of all three molecules was significantly inhibited in HepG2/ OXA/T cells, in which FGFR2 was silenced by FGFR2 shRNA. In the examined HepG2 cells, the FGFR2, p-ERK1/2 and ERCC1 expression levels demonstrated increasing trends in the OXA group and OXA + FGF7 group. Compared with the OXA group and OXA + FGF7 group, the FGFR2, p-ERK1/2, and ERCC1 expression levels were significantly lower in the OXA + emodin group, and these differences were statistically significant. In the HepG2/OXA/T cell line that was transfected with FGFR2 shRNA, the FGFR2, p-ERK1/2 and ERCC1 expression levels were significantly inhibited, but there were no significant differences in these expression levels among the OXA, OXA + FGF7 and OXA + emodin groups. CONCLUSION: Emodin markedly reversed OXA resistance by enhancing OXA DNA damage in HepG2/OXA cells, and the molecular mechanism was related to the inhibitory effect on ERCC1 expression being mediated by the FGFR2/ERK1/2 signaling pathway.
基金Supported by the National Science and Technology Support Program,No.2015BAI13B07
文摘AIM To investigate the interactions of the DNA repair gene excision repair cross complementing group 5(ERCC5) and the metabolic gene glutathione S-transferase pi 1(GSTP1) and their effects on atrophic gastritis(AG) and gastric cancer(GC) risk.METHODS Seven ERCC5 single nucleotide polymorphisms(SNPs)(rs1047768, rs2094258, rs2228959, rs4150291, rs4150383, rs751402, and rs873601) and GSTP1 SNP rs1695 were detected using the Sequenom MassA RRAY platform in 450 GC patients, 634 AG cases, and 621 healthy control subjects in a Chinese population.RESULTS Two pairwise combinations(ERCC5 rs2094258 and rs873601 with GSTP1 rs1695) influenced AG risk(P_(interaction) = 0.008 and 0.043, respectively), and the ERCC5 rs2094258-GSTP1 rs1695 SNP pair demonstrated an antagonistic effect, while ERCC5 rs873601-GSTP1 rs1695 showed a synergistic effect on AG risk OR = 0.51 and 1.79, respectively). No pairwise combinations were observed in relation to GC risk. There were no cumulative effects among the pairwise interactions(ERCC5 rs2094258 and rs873601 with GSTP1 rs1695) on AG susceptibility(P_(trend) > 0.05). When the modification effect of Helicobacter pylori(H. pylori) infection was evaluated, the cumulative effect of one of the aforementioned pairwise interactions(ERCC5 rs873601-GSTP1 rs1695) was associated with an increased AG risk in the case of negative H. pylori status(P_(trend)= 0.043).CONCLUSION There is a multifarious interaction between the DNA repair gene ERCC5 SNPs(rs2094258 and rs873601) and the metabolic gene GSTP1 rs1695, which may form the basis for various inter-individual susceptibilities to AG.
文摘Objective： To estimate the relationship between genetic polymorphisms of X-ray repair cross- complementing group 1 （XRCC1） and the susceptibility to childhood acute lymphoblastic leukemia （ALL）. Methods： Relevant case-control studies were enrolled in the meta-analysis. We applied Rev Man 4.2 software to pool raw data and test studies＇ heterogeneity and to calculate the incorporated odds ratio （OR） and 95% confidence interval （95% CI）. Results： Our data showed that the OR for the Gln allele of the Arg399Gln polymorphism, compared with the Arg allele, was 1.35 （95% CI, 1.16-1.57; P〈0.0001） for childhood ALL patients. Similarly, the homozygous genotype Gln/Gln and heterozygous genotype Arg/Gln both significantly increased the risk of childhood ALL compared with the wild genotype Arg/Arg （OR =1.58; 95% CI, 1.13-2.21; P=0.008; OR =1.51; 95% CI, 1.21-1.87; P=0.0002）. The dominant model of Arg399Gln was associated with childhood ALL risk （OR =1.54; 95% CI, 1.25-1.89; P〈0.0001）. The ethnic subgroup analysis demonstrated that the Gln allele in all five ethnic groups was prone to be a risk factor for childhood ALL just with different degrees of correlation while Arg194Trp SNP showed a protective or risk factor or irrelevant thing in different races. Conclusions： XRCC1 399 polymorphism may increase the risk of childhood ALL. Different ethnic groups with some gene polymorphism have different disease risks.
基金Supported by: the National Natural Science Foundation of China, No. 30571790
文摘BACKGROUND： Recent studies have shown that the selective inhibitor of c-Jun N-terminal kinases （JNKs） signaling pathway, SP600125, exhibits neuronal protective effects in a rat model of brain ischemia/reperfusion. OBJECTIVE： To determine the mechanisms of neuroprotective effects of SP600125 in a rat model of brain ischemia/reperfusion, and determine the role of the JNK signaling pathway in SP600125-induced effects. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Animal Experiment Center, Medical School of Xi＇an Jiaotong University from June 2007 to September 2008. MATERIALS： SP600125 was provided by Biosource, USA; rabbit anti-phospho-JNK （Thr183/Tyr185） polyclonal antibody from Cell Signaling Technology, USA; rabbit anti-X-ray repair cross-complementing protein 1 （XRCC1） and anti-Ku70 polyclonal antibodies from Santa Cruz Biotechnology, USA; and TUNEL kit from Beijing Huamei Biology, China. METHODS： A total of 108 male, 4-month-old, Sprague Dawley rats were randomly assigned to three groups, with 36 rats per group. The sham operation group and ischemia/reperfusion group （I/R group） were intracerebroventricularly injected with 10 μL 1% DMSO. The SP600125-treated group （pre-SP group） was given 10 μL SP600125 （3 μg/μL）. Thirty minutes later, brain ischemia was induced in the I/R and pre-SP groups using the four-vessel occlusion method. Specifically, whole brain ischemia was induced for 6 minutes, and the clips were released to restore carotid artery blood flow. Rats from each group were observed at 2, 6, 12, 24, 48, and 72 hours, with 6 rats for each time point. The sham operation group was treated with the same surgical exposure procedures, with exception of occlusion of the carotid artery. MAIN OUTCOME MEASURES： Hematoxylin-eosin staining was used to observe neuronal survival in the hippocampal CA1 region, TUNEL was used to detect apoptosis in the hippocampal CA1 region, and immunohistochemistry was used to detect expression of phospho-JNK, XRCC1, and Ku70. RESULTS： Following brain ischemia/reperfusion, neuronal survival significantly decreased, and the number of apoptotic cells significantly increased （P 〈 0.01）. Compared with the I/R group, neuronal survival significantly increased in the pre-SP group, and the number of apoptotic cells significantly decreased （P 〈 0.01）. Expression of phospho-JNK increased, and XRCC1 and Ku70 significantly decreased （P 〈 0.05） following ischemia/reperfusion. Compared with the I/R group, expression of phospho-JNK decreased, and XRCC1 and Ku70 significantly increased in the pre-SP group （P 〈 0.05）. Correlation analysis revealed an inverse correlation between phospho-JNK gray value and XRCC1 and Ku70 gray values in the hippocampal CA1 region （r = -0.983, -0.953, P 〈 0.01）. CONCLUSION： SP600125 treatment decreased apoptosis induced by global brain ischemia/reperfusion in the rat hippocampal CA1 region. Results suggested that the neuroprotective effects were due to inhibited phosphorylation of JNK and reduced down-regulation of XRCC1 and Ku70.
文摘Background Several studies have evaluated the association between polymorphisms of encoding excision repair cross complementation group 1 （ERCC1） enzyme and lung cancer risk in diverse populations but with conflicting results.By pooling the relatively small samples in each study, it is possible to perform a meta-analysis of the evidence by rigorous methods.Methods Embase, Ovid, Medline and Chinese National Knowledge Infrastructure were searched. Additional studies were identified from references in original studies or review articles. Articles meeting the inclusion criteria were reviewed systematically, and the reported data were aggregated using the statistical techniques of meta-analysis.Results We found 3810 cases with lung cancer and 4332 controls from seven eligible studies. T19007C polymorphism showed no significant effect on lung cancer risk （C allele vs. T allele： odds ratio （OR）=0.91, 95% confidence interval （CI）=0.80-1.04; CC vs. TT： OR=0.76, 95% CI=0.56-1.02; CC vs. （CT＋TT）： OR=0.96, 95% CI=-0.84-1.10）. Similarly,there was no significant main effects for T19007C polymorphism on lung cancer risk when stratified analyses by ethnicity （Chinese or Caucasian）. No significant association was found between C8092A polymorphism （3060 patients and 2729 controls） and the risk of lung cancer （A allele vs. C allele： OR=1.03, 95% CI=0.95-1.11; AA vs. CC： OR=1.08, 95% CI=-0.88-1.33; AA vs. （AC＋CC）： OR=1.08, 95% CI=-0.88-1.31）.Conclusion We found little evidence of an association between the T1900C or C8092A polymorphisms of ERCC 1 and the risk of lung cancer in Caucasian or Han Chinese people.
文摘Background：Conflicting results about the association between expression level of excision repair cross-complementation group 1 （ERCC1） and clinical outcome in patients with colorectal cancer （CRC） receiving chemotherapy have been reported.Thus,we searched the available articles and performed the meta-analysis to elucidate the prognostic role of ERCC1 expression in patients with CRC.Methods：A thorough literature search using PubMed （Medline）,Embase,Cochrane Library,Web of Science databases,and Chinese Science Citation Database was conducted to obtain the relevant studies.Pooled hazard ratios （HRs） or odds ratios （ORs） with 95% confidence intervals （CIs） were calculated to estimate the results.Results：A total of 11 studies were finally enrolled in this meta-analysis.Compared with patients with lower ERCC1 expression,patients with higher ERCC1 expression tended to have unfavorable overall survival （OS） （HR =2.325,95% CI：1.720-3.143,P 〈 0.001）,progression-free survival （PFS） （HR =1.917,95% CI：1.366-2.691,P 〈 0.001） and poor response to chemotherapy （OR =0.491,95% CI：0.243-0.990,P =0.047）.Subgroup analyses by treatment setting,ethnicity,HR extraction,detection methods,survival analysis,and study design demonstrated that our results were robust.Conclusions：ERCC1 expression may be taken as an effective prognostic factor predicting the response to chemotherapy,OS,and PFS.Further studies with better study design and longer follow-up are warranted in order to gain a deeper understanding of ERCC 1＇s prognostic value.
