BMI1 overexpression is correlated with a poor prognosis and immune infiltration in hepatocellular carcinoma

Background:Owing to the occurrence of primary or secondary tolerance,the efficacy of immunotherapy for hepatocellular carcinoma(HCC)patients is limited.Therefore,the mechanism underlying this tolerance needs to be further investigated.B cell–specific Moloney murine leukemia virus integration site 1(BMI1)is associated with cancer stem cell tumorigenesis,progression,and the maintenance of the self-renewal.However,the effect of BMI1 expression on immune infiltration and prognosis in HCC is still unclear.Methods:To assess the relationship between BMI1 expression and HCC prognosis and immune infiltration,the GEPIA database,TIMER database,and K-M plotter were used.TIMER database was used to determine the levels ofBMI1 in various tumor tissues and corresponding normal tissues,and examine the association between BMI1 expression and tumor-infiltrating immune cells.GEPIA database was applied to determine BMI1 expression in various tumor tissues and corresponding normal tissues.K-M Plotter was used to study the relationships among BMI1 expression,clinicopathological features,and survival rates.Results:BMI1 expression was markedly higher in various solid tumors compared with that in the respective normal tissues,including HCC,and high expression led to poor relapse-free survival and overall survival in HCC patients.BMI1 overexpression was also correlated with the infiltration of immune cells(eg,B cells,CD8+T cells,CD4+T cells,dendritic cells,neutrophils,and macrophages)and positively associated with different subsets of T cells,monocytes,and M1 macrophages,among others.Conclusions:This study demonstrates that high BMI1 expression is strongly correlated with immune infiltration and poor prognosis in HCC.Increased expression of BMI1 might thus be a potential mechanism of immune tolerance in this disease.

Influence of As_2O_3 combined with ginsenosides Rg3 on inhibition of lung cancer NCI-H1299 cells and on subsistence of nude mice bearing hepatoma

Objective:To study the effect of arsenic trioxide(As_2O_3)combined with ginsenosides Rg3 on inhibiting the NCI-H1299 lung cancer cells and subsistence in nude mice bearing hepatoma.Methods:MTT method was used to measure the inhibition effect of(As_2O_3)combined Rg3 on NC1-H1299 cells,and the proliferation inhibiting effect was observed via establishing the transplanted tumor model in vitro.A total of 40 tumor-bearing nude mice were randomly divided into normal saline group,(As_2O_3),Rg3 and As_2O_3+Rg3 group.Transplantation tumor model of lung cancer in nude mice was constructed,followed by injection of certain concentrations of normal saline,As_2O_3,ginseng saponin Rg3 and As_2O_3+Rg3 every day.The survival duration and the tumors size of the mice were recorded and the Kaplan-Meier curve was made;microscopic observation of apoptosis of tumor cells in vivo was done using TUNEL staining.Results:After 72 h of injection.inhibition rate of tumor cell in normal saline group,As_2O_3 group.Rg3 group and As_2O_3+Rg3 group was(5.66±0.31)%,(65.58±4.75)%,(44.69±3.32)%and(82.67±5.43)%,respectively.Inhibition rate of tumor cell in As_2O_3 group.Rg3 groap and As_2O_3+Rg3 group was significantly higher than that of normal saline group(P<0.01);inhibition rate of tumor cells of As_2O_3+Rg3 group was significantly higher than that of the two groups given As_2O_3 or Rg3 alone(P<0.01).The tumor volume of As_2O_3 group,Rg3 group and As_2O_3+Rg3 group shrank to(65.38±3.25)%,(77.68±3.43)%and(42.65±3.55)%of the original,tumor volume of saline group was 1.21 times of the original size(P<0.01);Median survival of saline group,Rg3 group,As_2O_3 group were significantly shorter than that of As_2O_3+Rg3 group(P<0.01);co-ordinated intervention ability of As_2O_3+Rg3 on NCI-H1299 cell was significantly higher than that of As_2O_3 or Rg3,separately.Conclusions:As_2O_3 combined with Rg3 can significantly inhibit prolifaration of NCI-H1299 cells in lung cancer,prolong survival fo tumor-bearing nude mice,and promote tumor cell apoptosis,and have significant effect on lung cancer treatment.

Formation and impact-induced separation of tandem EFPs

The formation and separation behaviors of tandem EFPs are studied by the combination of experiments and simulations.The results show that different formation and separation processes can be obtained by adjusting the double-layer liners,and simulations agree with experiments well.Then,the interaction process between the two liners is discussed in details,and the formation and separation mechanism are revealed.It can be found that there are four phases in the formation and separation processes,including impact phase,propulsion phase,slide phase and free flight phase.During the impact phase,the velocities of two liners rise in turns with kinetic energy exchange.In the propulsion phase,the axial impact becomes insignificant,but the radial interaction between two liners influences the appearance of tandem EFPs.Meanwhile,it should be mentioned that the inner surface of foregoing EFP remains to be in contact with the outer surface of following EFP in the propulsion phase,and the following one would continue to push the foregoing one for about 10μ to 20 μs,causing the velocities of following and foregoing EFPs gradually decreasing and increasing respectively.In the slide phase,an obvious relative movement occurs between the two EFPs,and there would be barely kinetic energy exchange.Then,the two EFPs separate gradually and get into the phase of free flight.Generally,if the outer and inner liners have the same thickness,the outer copper-inner copper liners form two long EFPs,the outer copper-inner steel liners become a foregoing short steel EFP and a following long copper EFP,and the outer steel-inner copper liners produce a foregoing long copper EFP and a following conical steel EFP.In addition,thickness match also has an important impact on formation appearance and separation process for both outer copperinner copper liners and outer steel-inner copper liners.With the thickness ratio of outer liner to inner liner decreasing,the length and length-diameter ratio of both foregoing and following EFPs increase gradually.

Effect of sevoflurane on tissue permeability of lung ischemia-reperfusion injury in rats

Objective:To investigate the effect of sevoflurane on tissue permeability of lung ischemiareperfusion injury(LIRI)in rats.Methods:A total of 45 wistar rats were randomly divided into3 groupsⅠ,Ⅱ,Ⅲ.Modified Eppinger method was adopted to establish the rat lung ischemiareperfusion injury model.GroupⅠserved as the control group,groupⅡas ischemia reperfusion group,groupⅢas sevoflurane ischemia-reperfusion group.Blood gas index,lung permeability index(LPI)change,lung tissue pathology change and lung water content were observed and compared between groups of rats at different time points.Results:During ischemia reperfusion,all rats kept balance of the MAP during different time points,SPO_2 of groupⅡandⅢdecreased significantly thanⅠgroup(P<0.05);after reperfusion lung permeability index in GroupⅡandⅢwas higher than the control group significantly(P<0.05),120 min after reperfusion LPI change and iujury of groupⅢwas significantly lower thanⅡgroup(P<0.05);interstitial and alveolar cavity effusion in of groupⅢwere lower than that of groupⅡ.Conclusions:Sevoflurane pretreatment can reduce the lung tissue permeability,and LIRI plays a protective role in LIRI.

Construction of targeted plasmid vector pcDNA3.1-Egr.1p-p16 and its expression in pancreatic cancer JF305 cells induced by radiation in vitro

AIM: To construct pcDNA3.1-Egr.1p-p16 recombinant plasmid and investigate the expression of p16 in pancreatic cancer JF305 cells induced by radiation and the feasibility of gene radiotherapy for pancreatic carcinoma. METHODS: Human p16 cDNA was ligated to the downstream of Egr-1 promotor to construct pcDNA3.1-Egr.1p-p16 plasmid by restriction enzyme digested. The recombined plasmids were transfected into pancreatic cancer JF305 cells with lipofectamine. p16 mRNA level was detected by RT-PCR. The expression of p16 after different doses of X-ray radiation was detected by Western blot technique. Cell survival was assessed by clonogenic assays and cell viability was analysed by trypen blue exclusion. Flow cytometry was performed to study the apoptosis of JF305 cells. RESULTS: Restriction enzyme digestion showed the correctly constructed pcDNA3.1-Egr.1p-p16. The p16 expression in cells transfected with pcDNA3.1-Egr.1p-p16 induced by different doses of radiation was higher than that in the control group (P < 0.05). Eight hours after 2 Gy X-ray radiation, the expression reached its peak(87.00 ng/L), and was signifi cantly higher than that in the control group (P < 0.0.5). Clonogenic analysis and trypan blue extraction test showed that the pcDNA3.1-Egr.1p-p16 transfer enhanced radiation-induced cell killing in p16-null JF305 cell lines. The induction of apoptosis was lower in combined transfection and irradiation group than that in irradiation alone. CONCLUSION: X-ray can induce the recombinant plasmid pcDNA3.1-Egr.1p-p16 expression in JF305 cells. The detection of dose and time provides an experimental basis for in vivo study in future.

Apoptotic pathway induced by diallyl trisulfide in pancreatic cancer cells

AIM:To investigate the effects of diallyl trisulfide(DATS),a garlic-derived organosulfur compound,in pancreatic cancer cells.METHODS:Human pancreatic cancer cells with wildtype p53 gene(Capan-2)and normal pancreatic epithelial cells(H6C7)were cultured in RPMI1640.DATS was prepared at a concentration of 100μmol/L.Cell viability was determined via the methyl thiazolyl tetrazolium assay.Apoptotic cells were detected by TUNEL assay.Cell cycle analysis was performed using flow cytometry.Protein expression was determined by Western blot.Bax and Bcl-2 expression was detected by immunofluorescence.Apoptosis genes and cell cycle were assessed by quantitative real-time polymerase chain reaction.RESULTS:DATS suppressed the viability of cultured human pancreatic cancer cells(Capan-2)by increasing the proportion of cells in the G2/M phase and induced apoptotic cell death.Western blot analysis indicated that DATS enhanced the expression of Fas,p21,p53and cyclin B1,but downregulated the expression of Akt,cyclin D1,MDM2 and Bcl-2.DATS induced cell cycle inhibition which was correlated with elevated levels of cyclin B1 and p21,and reduced levels of cyclin D1 in Capan-2 cells and H6C7 cells.DATS-induced apoptosis was markedly elevated in Capan-2 cells compared with H6C7 cells,and this was correlated with elevated levels of cyclin B1 and p53,and reduced levels of Bcl-2.DATS-induced apoptosis was correlated with downregulation of Bcl-2,Akt and cyclin D1 protein levels,and up-regulation of Bax,Fas,p53 and cyclin B protein levels in Capan-2 cells.CONCLUSION:DATS induces apoptosis of pancreatic cancer cells(Capan-2)and non-tumorigenic pancreatic ductal epithelial cells(H6C7).

Thiourea functionalized CdSe/CdS quantum dots as a fluorescent sensor for mercury ion detection

CdSe/CdS quantum dots （QDs） functionalized by thiourea （TU） were synthesized and used as a fluorescent sensor for mercury ion detection. The TU-functionalized QDs were prepared by bonding TU via electrostatic interaction to the core/shell CdSe/CdS QDs after capping with thioglycolic acid （TGA）. It was observed that the fluorescence of the functionalized QDs was quenched upon the addition of Hg^2＋. The quantitative detection of Hg^2＋ with this fluorescent sensor could be conducted based on the linear relationship between the extent of quenching and the concentration of Hg^2＋ added in the range of 1-300 μg.L^-1, A detection limit of 0.56 μg.L^-1 was achieved. The sensor showed superior selectivity for Hg^2＋ and was successfully applied to the determination of mercury in environmental samples with satisfactory results