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Nuclear factor-erythroid 2-related factor-2 (Nrf2) is an important transcription factor for cells to resist oxidative stress. It interacts with antioxidant response elements to induce the expression of downstream protective phase II detoxification enzymes and antioxidant enzymes and thus exerts a protective effect on cells. Oxidative stress is the common pathogenesis of many liver diseases, and the Nrf2-ARE antioxidant pathway is an important anti-oxidative stress pathway in vivo. It can induce the expression of downstream target genes and thus plays an important role in the development, progression, and prevention of liver diseases. This article briefly describes the mechanism of action of the Nrf2 antioxidant pathway in the development and progression of liver diseases and points out that Nrf2 may be a potential target for the prevention or treatment of liver diseases.
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Objective@#To study the effect of benazepril on the expression of nuclear factor E2 related factor 2 (Nrf2), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) and reactive oxygen species (ROS) concentration in rats with hepatic fibrosis and to explore the possible antifibrotic mechanism of benazepril.@*Methods@#Twenty-two healthy male Sprague-Dawley rats were randomly divided into 3 groups: control group (6 rats), model group (8 rats) and benazepril treatment group (8 rats). Two rats died during modeling and treatment in the model group and the benazepril treatment group, and a model of hepatic fibrosis induced by carbon tetrachloride (CCL4) was established. The rats in benazepril group were given benazepril for 8 weeks by gastric gavage. The assessment of liver tissue damage in each group was measured using conventional hematoxylin-eosin and Masson staining. The mRNA level of Nrf2, NOX4 in liver tissue was detected by RT-PCR, and serum ROS concentration was determined by colorimetry. All data were expressed in mean ± standard deviations, and were analyzed using SPSS21.0 statistical software. The data were compared using one-way analysis of variance, and the LSD-t method was used for pairwise comparison between the two groups. The correlation analysis was performed by Spearman’s correlation analysis.@*Results@#In the liver of the model group, with the aggravation of liver fibrosis the expression of Nrf2mRNA, NOX4 mRNA and ROS concentration were higher than control group [(4.01 ± 3.40), (31.78 ± 3.96), (1.82 ± 0.46) μg/ ml vs. (0.12 ± 0.11), (2.03 ± 0.31), (1.56±0.84) μg/ml, P < 0.05]. After benazepril treatment, NOX4 mRNA expression and ROS concentration were decreased than the model group [(15.93 ± 5.01), (0.78 ± 0.44) μg/ml vs. (31.78 ± 3.96), (1.82 ± 0.46) μg /ml, P < 0.05], while Nrf2 mRNA expression was higher than the model group [(6.69 ± 4.86) vs. (4.01 ± 3.40), P < 0.05]. There was a positive correlation between Nrf2 and NOX4, Nrf2 and ROS, and NOX4 and ROS (r = 0.616, 0.411, 0.802, P < 0.05).@*Conclusion@#Benazepril may exert an anti-hepatic fibrosis effect by activating Nrf2 expression, or may inhibit the ROS-mediated oxidative stress in response to NOX4.
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Objective@#To systematically evaluate the efficacy and safety of endoscopic resection and laparoscopic surgery for gastrointestinal stromal tumors(GIST) (diameter<3.5 cm).@*Methods@#According to the Cocharane system search strategy, Chinese and English literature comparing endoscopic with laparoscopic treatment of GIST published from January 2000 to March 2018 were collected. Ten articles meeting the inclusion criteria were included and analyzed with Revman 5.3.@*Results@#Of the 10 articles, 1 was a prospective randomized controlled trial and 9 were retrospective non-randomized controlled trials. The total number of patients was 1 062. There were 732 cases in the endoscopic treatment group, and 330 cases in the laparoscopic surgery group. The meta-analysis results showed that the endoscopic treatment group had shorter operation time (MD=-30.58 min, 95%CI: -39.31--21.84, P<0.05), less blood loss (MD=-12.99 mL, 95%CI: -16.40--9.57, P<0.05), shorter hospital stay (MD=-3.17 d, 95%CI: -4.76--1.59, P<0.05), and less total cost (MD=-1.63 ten thousand RMB, 95%CI: -2.42--0.84, P<0.05) than those of the laparoscopic group. But there were no significant differences in the positive rate of margin(RR=2.35, 95%CI: 0.52-10.69, P=0.27) or perioperative complications(RR=1.08, 95%CI: 0.48-2.42, P=0.85).@*Conclusion@#Existing studies have shown that endoscopic treatment for GIST is effective, minimally invasive, economical with better prognosis, ensuring complete resection.
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Objective To systematically evaluate the efficacy and safety of endoscopic resection and laparoscopic surgery for gastrointestinal stromal tumors(GIST)(diameter<3. 5 cm). Methods According to the Cocharane system search strategy,Chinese and English literature comparing endoscopic with laparoscopic treatment of GIST published from January 2000 to March 2018 were collected. Ten articles meeting the inclusion criteria were included and analyzed with Revman 5. 3. Results Of the 10 articles,1 was a prospective randomized controlled trial and 9 were retrospective non-randomized controlled trials. The total number of patients was 1062. There were 732 cases in the endoscopic treatment group,and 330 cases in the laparoscopic surgery group. The meta-analysis results showed that the endoscopic treatment group had shorter operation time (MD= -30. 58 min,95％CI:-39. 31--21. 84,P<0. 05),less blood loss (MD= -12. 99 mL, 95％CI:- 16. 40-- 9. 57,P < 0. 05),shorter hospital stay (MD = - 3. 17 d,95％CI:-4. 76--1. 59,P <0. 05),and less total cost (MD= -1. 63 ten thousand RMB,95％CI:-2. 42--0. 84,P<0. 05)than those of the laparoscopic group. But there were no significant differences in the positive rate of margin(RR = 2. 35, 95％CI:0. 52-10. 69,P= 0. 27)or perioperative complications(RR= 1. 08,95％CI:0. 48-2. 42,P= 0. 85). Conclusion Existing studies have shown that endoscopic treatment for GIST is effective,minimally invasive,economical with better prognosis,ensuring complete resection.
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Objective@#To investigate the effects of angiotensin II type 1 receptor antagonist valsartan on leptin, leptin receptor and collagen in rats with hepatic fibrosis.@*Methods@#Thirty-six male wistar rats were randomly divided into control group, model group and drug-treated group, with 12 rats in each group. Liver fibrosis models were made by subcutaneous injection of carbon tetrachloride on the dorsal of the rats, simultaneously gastric gavage with Valsartan and were killed at the end of 8th week. The degree of liver fibrosis was observed by HE and Masson staining. The serum leptin (LP) and TGFβ1 were determined by ELISA. Liver LP mRNA and leptin receptor mRNA (OB-R mRNA) were detected by RT-PCR. Liver LP, OB-R and collagen I were detected by Western blot. The data of multiple groups were analyzed by one-way analysis variance (ANOVA), and linear correlation was performed between serum LP and TGF β1.@*Results@#After the intervention of valsartan, HE and Masson staining showed that the degree of liver fibrosis was significantly reduced. The levels of serum LP and TGFβ1 in the control group were (18.92 ± 7.10) ng/ml and (9.13 ± 1.58) pg/ml respectively, which were significantly lower than those in the model group (46.92 ± 28.54) ng/ml and (16.39 ± 3.56) pg/ml, And (29.27 ± 7.27) ng/ml and (12.24 ± 2.94) pg/ml in the drug-treated group, respectively. The F values were 7.864 and 20.057 respectively. The P values were < 0.05. The differences were statistically significant. The relative expression levels of LP and OB-R mRNA in the control group were 0.35 ± 0.18 and 0.62 ± 0.18, respectively, which were significantly lower than those in the model group (1.79 ± 1.79 and 1.52 ± 1.44, and drug-treated group 0.48 ± 0.34 and 0.75 ± 0.26, respectively), F values = 6.914,3.894, P values were < 0.05, the differences were statistically significant. The relative expression levels of LP, OB-R and collaten I in liver were 0.71 ± 0.13, 0.81 ± 0.11 and 0.76 ± 0.13 in the model group, 0.97 ± 0.06, 1.04 ± 0.06, and 1.05 ± 0.04 respectively in the drug-treated group and 0.74 ± 0.05, 0.93 ± 0.05 and 0.91 ± 0.05. The F values were 15.425, 13.757 and 19.130 respectively in three groups (P < 0.001), the difference was statistically significant.@*Conclusion@#Valsartan, an angiotensin II type 1 receptor antagonist, can reduce the expression of leptin and leptin receptor, reduce the production of TGFβ1 and collaten I, and play an anti-hepatic fibrosis effect.
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Objective To investigate the expression of unfolded protein response (UPR) gene glucose regulated protein 78(GRP78) and X-box binding protein 1(XBP1) in esophageal squamous cell carcinoma, its effect on activation of the endoplasmic reticulum stress (ERS) and its mechanism in the growth of esophageal squamous cell carcinoma. Methods The expressions of GRP78 and XBP1 were detected by immunohistochemistry in 30 samples of esophageal squamous cell carcinoma and 30 samples of normal esophageal squamous epithelium. The correlation between expressions of both proteins and prognosis was analyzed. Results GRP78 positive rate was 83.3 %(25/30) in esophageal carcinoma, while the proportion was 20.0 %(6/30) in normal esophageal (χ2=25.833, P<0.05). XBP1 positive rate was 70.0 % (21/30) in esophageal carcinoma, while the proportion was 26.7%(8/30) in normal esophageal(χ2=20.872, P<0.05). The positive rates of GRP78 and XBP1 in invasive muscular layer of esophageal squamous cell carcinoma were significantly higher than those in invasive mucous layer. Conclusion GRP78 and XBP1 are highly expressed in esophageal squamous cell carcinoma, which may involve the occurrence and development of the esophageal carcinoma.