Protective effect of curcumin against liver warm ischemia/reperfusion injury in rat model is associated with regulation of heat shock protein and antioxidant enzymes

AIM： To investigate the hypothesis that the protective effects of curcumin in hepatic warm ischemia/reperfusion （I/R） injury are associated with increasing heat shock protein 70 （Hsp70） expression and antioxidant enzyme activity. METHODS： Sixty Sprague-Dawley male rats were randomly divided into sham, I/R, C ＋ I/R groups. The model of reduced-size liver warm ischemia and reperfusion was used. Curcumin （50 mg/kg） was administered by injection through a branch of superior mesenteric vein at 30 min before ischemia in C ＋ I/R group. Five rats were used to investigate the survival during 1 wk after operation in each group. Blood samples and liver tissues were obtained in the remaining animals after 3, 12, and 24 h of reperfusion to assess serum alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, liver tissue NO2- ＋ NO3-, malondialdehyde （MDA） content, superoxide dismutase （SOD）, catalase （CAT）, nitricoxide synthase （NOS） and myeloperoxidase （MPO） activity, HspT0 expression and apoptosis ratio. RESULTS： Compared with I/R group, curcumin pretreatment group showed less ischemia/reperfusioninduced injury. CAT and SOD activity and Hsp70 expression increased significantly. A higher rate of apoptosis was observed in I/R group than in C ＋ I/R group, and a significant increase of MDA, NO2^- ＋ NO3^- and MPO level in liver tissues and serum transaminase concentration was also observed in I/R group compared to C ＋ I/R group. Curcumin also decreased the activity of inducible NO synthase （iNOS） in liver after reperfusion,but had no effect on the level of endothelial NO synthase （eNOS） after reperfusion in liver. The 7 d survival rate was significantly higher in C ＋ I/R group than in I/R group. CONCLUSION： Curcumin has protective effects against hepatic I/R injury. Its mechanism might be related to the overexpression of Hsp70 and antioxidant enzymes.

Growth inhibition of hepatocellular carcinoma tumor endothelial cells by miR-204-3p and underlying mechanism

AIM: To investigate the mechanism by which miR-204-3p inhibits the growth of hepatocellular carcinoma (HCC) tumor endothelial cells (TECs).

Effect of microRNA-1 on hepatocellular carcinoma tumor endothelial cells

AIM: To investigate the effect of microRNA-1(miR-1) on tumor endothelial cells(TECs) of human hepatocellular carcinoma(HCC).METHODS: MiR-1 specific short hairpin RNA(shRNA)was synthesized and cloned into a recombinant lentiviral vector. TECs were then infected by the miRNA-1-shRNA recombinant lentivirus. TECs were divided into three groups: a control(CON) group consisting of normal TECs without lentiviral infection, a negative control(NC) group consisting of normal TECs infected with a negative control virus, and a microdown(MD) group consisting of normal TECs infected with the miR-1-inhibition virus containing the target gene. Silencing of miR-1 expression was quantified via quantitative reverse transcription-polymerase chain reaction(qRT-PCR). The proliferation of TECs was detected using MTT(Thiazolyl Blue Tetrazolium Bromide) assay; the observations were continued for 5 d, and the optical density value at 490 nm was detected every day. Apoptosis was detected via flow cytometry using Annexin V-APC single staining. The migration and invasion of TECs were detected using transwell assays.RESULTS: Lentiviral miR-1 shRNA was successfully transduced into TECs, and specifically silenced the expression of miR-1. The results of qRT-PCR showed that the expression of miR-1 was significantly decreased in the MD group(2-ΔΔCt = 0.57 ± 0.14)compared with the CON group(2-ΔΔCt = 1) and the NC group(2-ΔΔCt = 1.05 ± 0.13)(P < 0.01). The results of MTT assay showed that the cell proliferation was all significantly inhibited in the MD group in the 5days compared with the CON and NC groups(P <0.01). The results of flow cytometry showed that the apoptosis was significantly increased in the MD group(6.32% ± 0.33%) compared with the CONgroup(2.03% ± 0.30%) and the NC group(2.18% ±0.15%)(P < 0.01). The ability of cell migration was significantly inhibited in the MD group(62.0 ± 5.48)compared with the CON group(99.8 ± 3.11) and the NC group(97.2 ± 3.70)(P < 0.01). The ability of invasion of TECs was also significantly inhibited in the MD group(29.8 ± 2.39) compared with the CON group(44.6 ± 3.36) and the NC group(44.4 ± 5.17)(P <0.01).CONCLUSION: MiR-1 might be a potential tumor activator. Inhibiting its expression could decrease proliferation, induce apoptosis, and inhibit the migration and invasion of TECs of human HCC.

Treatment strategy for gallstone pancreatitis and the timing of cholecystectomy

AIM:To reviewed the literature and evaluated the scope and timing of the application of endoscopic retrograde cholangiopancreatography(ERCP)/endoscopic sphincterotomy(ES)and cholecystectomy.METHODS:A pooled odds ratio(OR)and a pooled mean difference with the 95%CI were used to assess the enumeration data of included studies.A pooled weighted mean difference(WMD)and a pooled mean difference with the 95%CI were used to assess the measurement data of included studies.Statistical heterogeneity was tested with theχ2 test.According to forest plots,heterogeneity was not significant,so the fixed effect model was adopted.The significance of the pooled OR was determined by the Z test and statistical significance was considered at P<0.05.RESULTS:Data were collected from two studies(353patients,142 in the early cholecystectomy group and211 in the delayed cholecystectomy group)regarding the length of hospital stay[The WMD was-2.87(95%CI:-3.36--2.39,P<0.01).Data were collected from four studies(618 patients,211 in the early cholecystectomygroup and 408 in the delayed cholecystectomy group)regarding perioperative complications(OR=0.94,95%CI:0.41-2.12,P>0.05).Data were collected from four studies(618 patients,211 in the early cholecystectomy group and 408 in the delayed cholecystectomy group)on the number of patients who underwent ERCP±ES postoperatively(OR=0.80,95%CI:0.45-1.41,P>0.05).CONCLUSION:Cholecystectomy offers better protection than ES against further bouts of pancreatitis in patients with gallstone pancreatitis,although ES is an acceptable alternative.