Hepatitis B virus induces expression of cholesterol metabolism-related genes via TLR2 in HepG2 cells

AIM:To investigate whether hepatitis B virus(HBV) exacerbates hepatic cholesterol accumulation,and explore the underlying mechanisms.METHODS:HepG2 cells were infected with adenovirus(Ad) containing 1.3-fold overlength HBV genome.Realtime polymerase chain reaction and Western blotting were used to measure mRNA and protein expression of target genes.Cholesterol accumulation was measured by fluorescence microscopy.Cell toxicity due to Ad-HBV treatment was determined by the mitochondrial tetrazolium assay.The protein levels of toll-like receptors(TLRs) were determined by Western blotting.RESULTS:Ad-HBV increased hepatic cholesterol accumulation and enhanced the mRNA and protein levels oflow-density lipoprotein receptor(LDLR) and 3-hydroxy3-methylglutharyl-coenzyme A reductase(HMGCoAr) mRNA and protein expression in HepG2 cells.In addition,these inductive effects were partly offset by suppressing TLR2 expression levels by small interfering RNA in HepG2 cells.CONCLUSION:Ad-HBV increases LDLR and HMGCoAr expression,resulting in exacerbated cholesterol accumulation in HepG2 cells,which was mediated via the TLR2 pathway.

Characteristics and pathological mechanism on magnetic resonance diffusion-weighted imaging after chemoembolization in rabbit liver VX-2 tumor model

AIM: To investigate dynamic characteristics and pathological mechanism of signal in rabbit VX-2 tumor model on diffusion-weighted imaging (DWI) after chemoembolization. METHODS: Forty New Zealand rabbits were included in the study and forty-seven rabbit VX-2 tumor models were raised by implanting directly and intrahepatically after abdominal cavity opened. Forty VX-2 tumor models from them were divided into four groups. DWI was performed periodically and respectively for each group after chemoembolization. All VX-2 tumor samples of each group were studied by pathology. The distinction of VX-2 tumors on DWI was assessed by their apparent diffusion coefficient (ADC) values. The statistical significance between different time groups, different area groups or different b-value groups was calculated by using SPSS12.0 software. RESULTS: Under b-value of 100 s/mm2, ADC values were lowest at 16 h after chemoembolization in area of VX-2 tumor periphery, central, and normal liver parenchyma around tumor, but turned to increase with further elongation of chemoembolization treatment. The distinction of ADC between different time groups was significant respectively (F = 7.325, P < 0.001; F = 2.496, P < 0.048; F = 6.856, P < 0.001). Cellular edema in the area of VX-2 tumor periphery or normal liver parenchyma around tumor, increased quickly in sixteen h after chemoembolization but, from the 16th h to the 48th h, cellular edema in the area of normal liver parenchyma around tumor decreased gradually and that in the area of VX-2 tumor periphery decreased lightly at, and then increased continually. After chemoembolization, Cellular necrosis in the area of VX-2 tumor periphery was more significantly high than that before chemoembolization. The areas of dead cells in VX-2 tumors manifested low signal and high ADC value, while the areas of viable cells manifested high signal and low ADC value. CONCLUSION: DWI is able to detect and differentiate tumor necrotic areas from viable cellular areas before and after chemoembolization. ADC of normal liver parenchyma and VX-2 tumor are influenced by intracellular edema, tissue cellular death and microcirculation disturbance after chemoembolization.

Characteristics of liver on magnetic resonance diffusion-weighted imaging:Dynamic and image pathological investigation in rabbit liver VX-2 tumor model

AIM: To investigate dynamical and image pathological characteristics of the liver on magnetic resonance (MR) diffusion-weighted imaging (DWI) in the rabbit VX-2 tumor model. METHODS: Forty New Zealand rabbits were included in the study and VX-2 tumor piece was implanted intrahepatically. Fifteen animals received two intrahepatic implantations while 25 had one intrahepatical implantation. DWI, T1- and T2-weighted of magnetic resonance imaging (MRI) were carried out on the 7th and the 14th d after implantation and DWI was conducted, respectively on the 21th d. Ten VX-2 tumor samples were studied pathologically. RESULTS: The rate of lump detected by DWI, T1WI and T2WI was 78.7%, 10.7% and 53.5% (χ2 = 32.61,P < 0.001) on the 7th d after implantation and 95.8%, 54.3% and 82.9% (χ2 = 21.50, P < 0.001) on the 14th d. The signal of most VX-2 tumors on DWI was uniform and it was equal on the map of apparent diffusion coefficient (ADC). The signal of VX tumors did not decrease on the 7th d after implantation, most of them slowly growing during the week following implantation without significant cell dying within the tumor. VX-2 tumors grew increasingly within 14 d after implantation but the signal of most VX-2 tumors on DWI or on the map of ADC was uniform or uneven and ADC of VX tumors decreased obscurely or slightly because tumor necrosis was still not obvious. On the 21th d after implantation, the signal of most VX-2 tumors on DWI or on the map of ADC was uneven because tumor necrosis was evident and ADC of VX-2 tumor necrotic areas decreased. The areas of viable cells in VX-2 tumors manifested a high signal on DWI and a low signal on the map of ADC. The areas of dead cells or necrosis in VX-2 tumors manifested low signals on DWI and low, equal or high signals on the map of ADC but they manifested high signals on DWI and on the map of ADC at the same time when the areas of necrotic tumor became liquefi ed or cystic. The border of tumors on DWI appeared gradually distinct and internal signals of tumor became progressively uneven. CONCLUSION: The manifestations of viable, necrotic and liquefi ed or cystic areas in VX-2 tumors on DWI are typical and DWI is of significant and potential values in clinical application in both the early detection and diagnosis of liver tumors.

Gene expression and MR diffusion-weighted imaging after chemoembolization in rabbit liver VX-2 tumor model

AIM: To investigate the dynamic characteristics and the correlation between PCNA, Bax, nm23, E-cadherin expression and apparent diffusion coefficient (ADC) on MR diffusion-weighted imaging (DWI) after chemoembolization in rabbit liver VX-2 tumor model. METHODS: Forty New Zealand rabbit liver VX-2 tumor models were included in the study. DWI was carried out periodically after chemoembolization. All VX-2 tumor samples in each group were examined by histopathology and Strept Avidin-Biotin Complex (SABC) immunohistochemical staining. RESULTS: The PCNA expression index in VX-2 tumors was higher than in the normal parenchyma around the tumor (P < 0.001). Nm23, Bax or E-caderin expression index in VX-2 tumors were lower than in the normal parenchyma around the tumor (all P < 0.001). PCNAand nm23 expression in the VX-2 tumor periphery first increased and then decreased (P < 0.001 and P = 0.03, respectively), while the expression of Bax and E-cadherin before and after chemoembolization was insignificant. When b-value was 100 s/mm2, there was a linear correlation between PCNA expression and ADC in the area of VX-2 tumor periphery (P < 0.001), and PCNA expression in VX-2 tumor periphery influenced the ADC. CONCLUSION: The potential of VX-2 tumor infiltrating and metastasizing decreases, while its ability to proliferate increases for a short time after chemoembolization. To some degree, the ADC value indirectly reflects the proliferation of VX-2 tumor cells.

A membrane-inspired algorithm with a memory mechanism for knapsack problems

Membrane algorithms are a class of distributed and parallel algorithms inspired by the structure and behavior of living cells. Many attractive features of living cells have already been abstracted as operators to improve the performance of algorithms. In this work, inspired by the function of biological neuron cells storing information, we consider a memory mechanism by introducing memory modules into a membrane algorithm. The framework of the algorithm consists of two kinds of modules (computation modules and memory modules), both of which are arranged in a ring neighborhood topology. They can store and process information, and exchange information with each other. We test our method on a knapsack problem to demonstrate its feasibility and effectiveness. During the process of approaching the optimum solution, feasible solutions are evolved by rewriting rules in each module, and the information transfers according to directions defined by communication rules. Simulation results showed that the performance of membrane algorithms with memory cells is superior to that of algorithms without memory cells for solving a knapsack problem. Furthermore, the memory mechanism can prevent premature convergence and increase the possibility of finding a global solution.