Dihydromyricetin inhibits migration and invasion of hepatoma cells through regulation of MMP-9 expression

AIM:To investigate the effects of dihydromyricetin(DHM)on the migration and invasion of human hepatic cancer cells.METHODS:The hepatoma cell lines SK-Hep-1 and MHCC97L were used in this study.The cells were cultured in RPIM-1640 medium supplemented with 10%fetal bovine serum at 37℃in a humidified 5%CO2incubator.DHM was dissolved in dimethyl sulfoxide and diluted to various concentrations in medium before applying to cells.MTT assays were performed to measure the viability of the cells after DHM treatment.Wound healing and Boyden transwell assays were used to assess cancer cell motility.The invasive capacity of cancer cells was measured using Matrigel-coated transwell chambers.Matrix metalloproteinase(MMP)-2/9 activity was examined by fluorescence analysis.Western blot was carried out to analyze the expression of MMP-2,MMP-9,p-38,JNK,ERK1/2 and PKC-δproteins.All data were analyzed by Student’s t tests in GraphPad prism 5.0software and are presented as mean±SD.RESULTS:DHM was found to strongly inhibit the migration of the hepatoma cell lines SK-Hep-1(without DHM,24 h:120±8μmol/L vs 100μmol/L DHM,24h:65±10μmol/L,P<0.001)and MHCC97L(without DHM,24 h:126±7μmol/L vs 100μmol/L DHM,24h:74±6μmol/L,P<0.001).The invasive capacity of the cells was reduced by DHM treatment(SK-Hep-1cells without DHM,24 h:67±4μmol/L vs 100μmol/L DHM,24 h:9±3μmol/L,P<0.001;MHCC97L cells without DHM,24 h:117±8μmol/L vs 100μmol/L DHM,24 h:45±2μmol/L,P<0.001).MMP2/9 activity was also inhibited by DHM exposure(SK-Hep-1 cells without DHM,24 h:600±26μmol/L vs 100μmol/L DHM,24 h:100±6μmol/L,P<0.001;MHCC97L cells without DHM,24 h:504±32μmol/L vs 100μmol/L DHM 24 h:156±10μmol/L,P<0.001).Western blot analysis showed that DHM decreased the expression level of MMP-9 but had little effect on MMP-2.Further investigation indicated that DHM markedly reduced the phosphorylation levels of p38,ERK1/2 and JNK in a concentration-dependent manner but had no impact on the total protein levels.In addition,PKC-δprotein,a key protein in the regulation of MMP family protein expression,was up-regulated with DHM treatment.CONCLUSION:These findings demonstrate that DHM inhibits the migration and invasion of hepatoma cells and may serve as a potential candidate agent for the prevention of HCC metastasis.

The efficacy and safety of clopidogrel and aspirin in coronary heart disease with angina pectoris: a systematic review and meta-analysis

Background:To assess the efficacy and safety of clopidogrel combined with aspirin for angina pectoris.Methods:Randomized controlled trials were searched in PubMed,Excerpta Medica Database,the Cochrane Library,China National Knowledge Infrastructure,WANFANG databases and VIP databases from inception to February,2020.Methodological quality was evaluated by the tool of Cochrane collaboration.The meta-analysis was performed in the RevMan 5.3.Results:Fourteen randomized controlled trials with a total of 1,130 participants were included.Meta-analysis showed that for patients with angina pectoris,clopidogrel combined with aspirin had better clinical efficacy than aspirin alone(RR=1.26,95%CI:1.19-1.32,P<0.00001);on the interval time,duration and frequency of angina attack,clopidogrel and aspirin had better effect than aspirin alone(MD=2.09,95%CI:2.07-2.11,P<0.00001;MD=−2.48,95%CI:−3.12 to−1.84,P<0.00001;MD=−1.47,95%CI:−2.59 to−0.35,P=0.01,respectively).Moreover,the available data showed that aspirin and clopidogrel for patients with coronary heart disease with angina pectoris were safer than aspirin alone(RR=0.41,95%CI:0.27-0.61,P<0.0001).Conclusion:Clopidogrel combined with aspirin could be effective for patients with angina pectoris,meanwhile,it is important to be aware of the potential side effects.

Dynamic Mechanical Behavior and Hypervelocity Impact Performance of an Al-Based Nanocrystalline Alloy

In a wide strain rate range from 10^-5 to 10^3s^-1, the deformation behavior of an Al-based nanocrystalline alloy was investigated. After fracture, the debris collected was used for statistical analysis, which is expected to reflect the profile of the fracture behavior of the alloy. The energy absorption of alloy at different strain rates was elucidated on account of mass distribution of debris. Based on the parameters obtained by the compression experiment at different strain rates, the numerical simulation experiment was carried out to evaluate the performance of Al-based nanocrystalline alloy as spacecraft shielding. The results suggest that Al-based nanocrystalline alloys have better shield performance than alu- minum alloy under the identical areal density at velocity of 1-7 km/s. The better shield performance is attributed to high fracture strength, high hardness and low toughness of Al-based nanocrystalline alloy as compared with those of aluminum alloy.