ObjectiveTo investigate the expression of tripartite motif 21 (TRIM21) in gastric cancer tissues and its relationship with clinical pathological characteristics and clinical prognosis.MethodsPublic database was used to analyze the expression level of TRIM21 in gastric cancer tissues and the relationship between its expression and clinical prognosis. Gene set enrichment analysis (GSEA) was used to analyze the signaling pathways that TRIM21 might participate in. The expressions of TRIM21 in 80 gastric cancer tissues and 30 para-cancer tissues were detected by immunohistochemical staining, and the relationship between TRIM21 expression and clinicopathologic characteristics was analyzed.ResultsTRIM21was significantly low-expression in gastric cancer tissues, and the clinical prognosis of patients with low TRIM21 expression was significantly worse (P<0.05); GSEA showed that TRIM21 was involved in the regulation of helper T cell differentiation in gastric cancer patients (P<0.000 1, FDR<0.000 1).ConclusionsTRIM21 is poorly expressed in gastric cancer tissues and indicates the poor clinical prognosis. Moreover, TRIM21 is involved in the regulation of helper T cell differentiation and has a negative regulatory effect on the occurrence and development of gastric cancer.
Objective To investigate the development and significance of the expression of early growth response gene-1 （EGR-1） in autogenous vein graft in rats and detect the role of it in intimal hyperplasia. Methods Autogenous vein graft model was established in 90 Wistar rats, transplanting the right jugular vein to infra renal abdominal aorta by microsurgical technique. The vein graft samples were harvested at hour 1, 2, 6 and 24, day 3, 7,14, 28 and 42 after procedure. Normal vein as control group. Egr-1 mRNA was measured by reverse transcription-PCR and in situ hybridization. Western blot and immunohistochemistry were used to detect the protein expression of Egr-1. Results Intimal hyperplasia reached peak at day 28 after autogenous vein graft surgery. Egr-1 mRNA and Egr-1 protein hadn’t been found in the normal vein. The expressions of Egr-1 mRNA and Egr-1 protein had biphasic changes. By reverse transcription-PCR and in situ hybridization, we found that the level of Egr-1 mRNA rose at 1 hour after graft, the expression of Egr-1 mRNA was (35±7)%. Decline at hour 6， 24 and day 3, the positive rates of Egr-1 mRNA were (8±2)%, (8±6)% and (8±4)% respectively. Reincrease at day 7, a peak at day 28, the positive rate of Egr-1 mRNA was (45±6)% (compared with other phase, P＜0.01). At day 42, the expression of Egr-1 mRNA declined again. Immunohistochemical staining and Western blot revealed Egr-1 protein had expressed at hour 2 early phase, the expression of Egr-1 protein was (30±5)%, and until to hour 6. The level of Egr-1 protein was decrease at hour 24 and day 3, the positive rates were (7±3)% and (7±8)% respectively. A peak at day 28, the positive rate of Egr-1 protein was (40±9)% (compared with other phase, P＜0.01). We found that immu-noreative Egr-1 located vascular smooth muscle cells （VSMCs） and monocytes/macrophages in tunica media at the early phase of day 7 and 14, and in neointimal and medial VSMCs at later phase of day 28. Egr-1 was also present in the endoluminal endothelial cells. Conclusion In autogenous vein graft, Egr-1 plays an important role in the proliferation of VSMCs. Egr-1 may become a new target for the prevention and therapy of intimal hyperplasia, stenosis and emphraxis after vein graft.
Objective To understand breast cancer 1 (BRCA1) gene and relationship between BRCA1 gene and breast cancer, and analyze its effect on clinical comprehensive therapy of breast cancer. Method The domestic and international studies relevant BRCA1 and breast cancer in recent years were reviewed and summarized. Results BRCA1, a tumor suppressor gene, its mutations caused structural changes and functional abnormalities, which were closely related to breast cancer. And the expression situation and mutation of BRCA1 were associated with the therapeutic effect. Conclusions Mutation of BRCA1 is closely related to occurrence and development of breast cancer in female. Comprehensive therapy ideas should be found in clinical therapy according to expression or mutation of BRCA1. Further research on BTCA1 is beneficial to explore gold standard for treatment of breast cancer.
Objective To investigate the relationship between human leukocyte antigen(HLA)-B51 and Behcet′s disease (BD) with uveities. Methods HLA-A and HLA-B antigen of 27 pateints with BD and 30 healthy persons were detected by microly mphocyte toxicity asssay. HLA-B51 allele (HLA-B5101-B5107) in BD patients with positive HLA-B51 antigen and the controls was detected by polymerase chain reaction-sequence specific primer(PCR-SSP). Results The positive rate of HLA-B51 was 63% and 16.7% in BD patients and the controls, respectively (χ2=12.9, P＜0.001, Pc＜0.05,RR=8.5). Uveities was found in 11 out of 27 BD patients with uveitis. No relativity was found between HLA-B51 and uveitis in BD patients(RR=2.07,χ2=0.759,P＞0.25),and weak association was found between HLA=B5101 and uveitis (RR=2.67, χ2=1.395, P＞0.10). Conclusions HLA-B51 might be a susceptible gene for BD, and there was a weak association between HLA-B51(HLA-B5101) and BD patients with uveitis.(Chin J Ocul Fundus Dis，2004，20：203-205)
Objective To investigate the expression of transcriptional factors zinc finger Krüppel like transcription factor 2 ( Klf2) and NF-E2 related factor 2 ( Nrf2) /BTB CNC homology 1 ( Bach1) in rat bronchial epithelial cells stimulated by cigarette smoke extract ( CSE) , and explore the regulatingmechanism of γ-glutamylcysteine synthetase ( γ-GCS) expression in the oxidative condition. Methods Rat bronchial epithelial cells were harvested using enzyme digestion method, and intervened by 10% CSE for 6 hours. Then γ-GCS activity was detected by two enzymes method, and the nuclear transfer of Nrf2 /Bach1 in cells was detected by immunohistochemistry. Western blot and reverse transcription-polymerase chain reaction ( RT-PCR) techniques were used for detecting the protein and mRNA expressions of Klf2, Nrf2, Bach1, and γ-GCS in the cells. Results The γ-GCS activity was elevated in the CSE group. Immunohistochemical results showed that Nrf2 translocated from cytoplasm to nucleus in response to stimulation by CSE. On the contrary, Bach1 translocated from nucleus to cytoplasm in the same condition. Western blot results showed that protein levels of Klf2, Nrf2, Bach1, and γ-GCS were higher in the CSE group than those in the control group ( Plt;0.05) . RT-PCR results were the same as the Western blot results ( Plt;0.05) . Linear correlation analysis showed that γ-GCS expression was positively correlated with Klf2, Nrf2, and Bach1 ( Plt;0. 05) . Conclusion CSE might regulate the expression of γ-GCS through the transcription factors of Klf2, Nrf2, and Bach1.
Objective To investigate and analyze the relationships among glucagon-like peptide-1 (GLP-1) level, chronic inflammation, and atherosclerosis in patients with non-alcoholic fatty liver disease (NAFLD). Methods From October 2016 to February 2017, using cross-sectional investigation, the GLP-1 level, chronic inflammation, and atherosclerosis were investigated in 80 subjects (40 NAFLD patients in NAFLD group, and 40 non-fatty liver disease participants in control group) who underwent physical examination at Xi’an Road Community Hospital. Results Compared with those in the control group, GLP-1 fasting level in patients with NAFLD [(9.09±1.03) vs. (9.15±1.06) pmol/L, P=0.807] and postprandial plasma GLP-1 [(15.96±3.37) vs. (17.46±4.76) pmol/L, P=0.108] had no changes. The correlations of GLP-1 level with chronic inflammation and insulin resistance (IR) were not significant either. The increased risk of carotid intima-media thickness related cardiovascular disease (CVD) in the NAFLD group was greater than that in the control group, and the difference was statistically significant [22 (55.0%)vs.13 (32.5%), P=0.043]. When the plasma lipoprotein-associated phospholipase A2 level increased, the risk of NAFLD increased [odd ratio (OR)=1.16, 95% confidence interval (CI) (1.02, 1.32), P=0.023]. Plasma ceramide kinase (CERK) in the NAFLD group was lower than that in the control group, and the difference was statistically significant [(12.36±2.45) vs. (18.33±3.71) ng/mL, P<0.001]. When the plasma CERK level of the fasting plasma was elevated, the risk of NAFLD decreased [OR=0.30, 95%CI (0.12, 0.78), P=0.014]. The homeostasis model assessment of insulin resistance (HOMA-IR) in the NAFLD group was higher than that in the control group, and the difference was statistically significant (2.46±2.53 vs. 1.11±0.66, P=0.002). The Matsuda index in the NAFLD group was less than that in the control group, and the difference was statistically significant (5.88±4.09 vs. 10.46±7.90, P=0.002). When HOMA-IR increased, the risk of NAFLD increased [OR=2.75, 95%CI (2.49, 3.12), P=0.036]. Conclusions Plasma GLP-1 level is not a sensitive indicator of chronic inflammation and IR in patients with NAFLD. Patients with NAFLD are in an increased risk of atherosclerosis and CVD. It suggests that NAFLD might be involved in chronic inflammation and IR. Chronic inflammation can cause IR, and then chronic inflammation and IR can cause NAFLD and subclinical atherosclerosis. In return for this, NAFLD increases chronic inflammation and IR.
ObjectiveTo summarize the research advances of pyroptosis in hepatic ischamia-reperfusion injury (IRI).MethodThe literatures about the studies of mechanism of pyroptosis in hepatic IRI were retrieved and analyzed.ResultsPyroptosis, also known as inflammatory necrocytosis, was proven to play an important role in the hepatic IRI. When hepatic ischemia-reperfusion occurred, the classical pathway of pyroptosis dependenting on caspase-1 and the non-classical pathway of pyroptosis dependenting on caspase-11 were initiated by specific stimulants, and leaded to the activation of gasdermin D, releases of proinflammatory factors such as interleukin-1β, interleukin-18, etc., and the recruitment and activation of neutrophils. Consequently, pyroptosis caused more severe hepatic inflammation and aggravated existing cell injury and dysfunction of liver during hepatic IRI.ConclusionsPyroptosis plays an important role in liver IRI. Further researches about mechanism of pyroptosis will be beneficial to the prevention and treatment of the pyroptosis of related diseases.
ObjectiveTo explore the biological functions of Kip1 ubiquitylation-promoting complex 2 (KPC2) in the repair process of spinal cord injury (SCI) by studying the expression and cellular localization of KPC2 in rat SCI models. MethodsFifty-six adult Sprague-Dawley rats were randomly divided into 2 groups: in the control group (n=7), simple T9 laminectomy was performed;in the experimental group (n=49), the SCI model was established at T9, 7 rats were used to detect follow indexs at 6 hours, 12 hours, 1 day, 3 days, 5 days, 7 days, and 14 days after SCI. Western blot analysis was used to detect the protein expressions of P27kip1, KPC2, CyclinA and proliferating cell nuclear antigen (PCNA) after SCI. Immunohistochemistry was used to observed the cellular localization of KPC2 after SCI, double-labeling immunofluorescence staining to observe the co-localization of KPC2 with neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP) and PCNA. in vitro astrocytes proliferation model was used to further validate these results, Western blot to detect KPC2, P27kip1, and PCNA expressions. The interaction of P27kip1, KPC1, and KPC2 in cell proliferation was analyzed by co-immunoprecipitation. ResultsThe Western blot analysis showed a significant down-regulation of P27kip1 and a concomitant up-regulation of KPC2, CyclinA, and PCNA after SCI. Immunohistochemistry staining revealed a wide distribution of KPC2 positive signals in the gray matter and white matter of the spinal cord. The number of KPC2 positive cells in the experimental group was significantly higher than that in the control group (t=10.982, P=0.000). Double-labeling immunofluorescence staining revealed the number of KPC2/NeuN co-expression cells in the gray matter of spinal cord was (0.43±0.53)/visual field in the control group and (0.57±0.53)/visual field in the experimental group, showing no significant difference (t=0.548, P=0.604);in the white matter of spinal cord, the number of KPC2/PCNA co-expression cells was (3.86±0.90)/visual field in the control group and (0.71±0.49)/visual field in the experimental group, showing significant difference (t=7.778, P=0.000). And then, the number of KPC2/PCNA co-expression cells were (0.57±0.53)/visual field in the control group and (5.57±1.13)/visual field in the experimental group, showing significant difference (t=8.101, P=0.000). Concomitantly, there was a similar kinetic in proliferating astrocytes in vitro. The Western blot analysis showed a significant down-regulation of P27kip1 and a concomitant up-regulation of KPC2 and PCNA after serum stimulated. Co-immunoprecipitation demonstrated increased interactions between P27kip1, KPC1, and KPC2 after stimulation. ConclusionThe up-regulated expression of KPC2 after SCI is related to the down-regulation of P27kip1, this event may be involved in the proliferation of astrocytes after SCI.
Objective To systematically review the correlation between polymorphism of DNA methyltransferase 1(DNMT1) rs16999593 and the susceptibility of breast cancer. Methods Databases such as PubMed, EMbase, Web of Science, Chinese Biomedical Literature Database, CNKI, WanFang, and VIP database were searched from inception to Mar. 2017 to collect case-control studies on the correlation between DNMT1 rs16999593 C/T polymorphism and the susceptibility of breast cancer. Two reviewers independently identified the literatures according to inclusion and exclusion criterias, extracted data, and assessed the quality of the included studies. The meta-analysis was performed by using RevMan 5.3 software. Results A total of 5 studies involving 1 741 cases and 1 917 control subjects were included. The results of meta-analysis showed that, dominate model ［TT+TC vs. CC: OR=0.63, 95% CI was (0.30, 1.30), P=0.21］, homozygous model ［TT vs. CC: OR=1.01, 95% CI was (0.70, 1.47), P=0.95］, heterozygous model ［TC vs. CC: OR=0.44, 95% CI was (0.18, 1.04), P=0.06］, and additive model ［T vs. C: OR=1.29, 95% CI was (0.90, 1.86), P=0.16］ were not significantly related to breast cancer, but recessive gene model was related to breast cancer ［TT vs. TC+CC: OR=1.74, 95% CI was (1.01, 3.00), P=0.04］. Conclusion The current studies showed that, DNMT1 rs16999593 TT genotype decreases the susceptibility of breast cancer.
Objective To investigate the role and mechanism of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) in the activation of aortic valve interstitial cells (AVICs) in aortic stenosis. Methods Isolating primary AVICs and stimulating their activation with transforming growth factor β1 (TGF-β1, 30 ng/mL), the expression of PGC-1α was detected. The activation of AVICs induced by TGF-β1 was observed after overexpression of PGC-1α by adenovirus or inhibition of PGC-1α function by GW9662. The possible downstream molecular mechanism of PGC-1α in AVICs activation was screened. Finally, the phenotype was further verified in primary human AVICs. Results The expression of PGC-1α decreased after the activation of AVICs induced by TGF-β1 (control group: 1.00±0.18; 24 h: 0.31±0.10; 48 h: 0.32±0.06; 72 h: 0.20±0.07; P<0.05). Specific overexpression of PGC-1α by adenovirus inhibited the activation of AVICs induced by TGF-β1 stimulation (periostin: 3.17±0.64 vs. 1.45±0.54, P<0.05; α-smooth muscle actin: 0.77±0.11 vs. 0.28±0.06, P<0.05). On the contrary, inhibition of PGC-1α function by GW9662 promoted the activation of AVICs (periostin: 2.20±0.68 vs. 7.99±2.50, P<0.05). Subsequently, it was found that PGC-1α might inhibit the activation of AVICs through downregulating the expression of calcium/calmodulin-dependent protein kinase (CAMK1δ) (0.97±0.04 vs. 0.74±0.11, P<0.05), and downregulating the expression of CAMK1δ alleviated the activation of AVICs (periostin: 1.76±0.11 vs. 0.99±0.20, P<0.05). The possible mechanism was that the activation of mammalian target of rapamycin (mTOR) signaling pathway was inhibited by reducing the accumulation of reactive oxygen species (ROS) (778.3±139.4 vs. 159.3±43.2, P<0.05). Finally, the protective effect of PGC-1α overexpression was verified in the activated phenotype of human AVICs (periostin: 2.73±0.53 vs. 1.63±0.14, P<0.05; connective tissue growth factor: 1.27±0.04 vs. 0.48±0.09, P<0.05). Conclusions The expression of PGC-1α significantly decreases during the activation of AVICs induced by TGF-β1. The overexpression of PGC-1α significantly inhibites the activation of AVICs, suggesting that PGC-1α plays a protective role in the activation of AVICs. The possible mechanism is that PGC-1α can inhibit the activation of CAMK1δ-ROS-mTOR pathway. In conclusion, interventions based on PGC-1α expression levels are new potential therapeutic targets for aortic stenosis.