Dynamic enhancing vascular pattern of intrahepatic peripheral cholangiocarcinoma on contrast-enhanced ultrasound: the influence of chronic hepatitis and cirrhosis.

PURPOSE: To analyse the dynamic enhancing features by real-time contrast-enhanced ultrasound (CEUS) of intrahepatic peripheral cholangiocarcinoma (ICC) in patients with chronic hepatitis and cirrhosis. MATERIALS AND METHODS: CEUS was performed by using contrast pulse sequencing (CPS) imaging with mechanical index of <0.2 after injection of 2.4 mL of contrast agent. CEUS images of histologically confirmed ICC in 54 patents (15 patents with chronic hepatitis B, 16 patents with cirrhosis, and 23 patents with normal underlying liver) were analyzed. RESULTS: Heterogeneous hyperenhancement was more frequently identified in ICC with chronic hepatitis (9 of 15, 60.0%, p = 0.000) and cirrhosis (8 of 16, 50.0%, p = 0.010) than in patients with normal liver (6 of 23, 26.1%) during arterial phase. The majority of ICC in patients with normal liver displayed peripheral hyperenhancement (13 of 23, 56.5%), than in patients with chronic hepatitis (4 of 15, 26.7%, p = 0.000) and cirrhosis (5 of 16, 31.3%, p = 0.001). Intense contrast uptake during the arterial phase (heterogeneous hyperenhancement or global hyperenhancement) followed by washout in venous phases was more frequently displayed in ICC patients with chronic hepatitis (11 of 15, 73.3%, p = 0.000) and in patients with cirrhosis (11 of 16, 68.8%, p = 0.000) than in ICC patients with normal underlying liver (8 of 23, 34.8%). CONCLUSION: The enhancing vascular pattern of ICC on CEUS in patients with chronic hepatitis and cirrhosis is different from that in ICC without underlying liver disease. The enhancing vascular pattern is indistinguishable from HCC on CEUS in most ICC patients with chronic hepatitis or cirrhosis.

[The new technology of enhanced radiofrequency ablation is safe and effective for treating giant hepatic hemangioma].

OBJECTIVE: To determine the safety and efficacy of the enhanced radiofrequency ablation (RFA) new technology for treatment of giant hepatic hemangiomas. METHODS: From August 2010 to September 2011, 30 patients with giant hepatic hemangiomas (average diameter: 7.7+/-1.9 cm, range: 5.0 to 12.8 cm) were treated with enhanced RFA. The original lesion diameter, enhanced radiofrequency duration, and cases of RFA-induced burning were recorded. Cases requiring a second RFA treatment were also recorded. Correlation analysis was carried out to determine the association of enhanced RFA with adverse events and change in lesion diameter. RESULTS: The rate of completely destroyed lesions by enhanced RFA was 70.96%, and the total rate of reduced lesions was 87.1%. No severe adverse events occurred. The duration of enhanced radiofrequency correlated positively with the original lesion diameter (r=0.687, P less than 0.01). The enhanced RFA treatment significantly reduced the average lesion diameter (follow-up: 6.2+/-1.8 cm; t=6.417, P less than 0.01). CONCLUSION: The new minimally-invasive technology of enhanced radiofrequency ablation is effective and safe for treating giant hepatic hemangiomas and produces an obvious, short-term curative effect.

Study on the Fracture Toughness of Softwood and Hardwood Estimated by Boundary Effect Model.

The tensile strength and fracture toughness of softwood and hardwood are measured by the Boundary Effect Model (BEM). The experimental results of single-edge notched three-point bending tests indicate that the BEM is an appropriate method to estimate the fracture toughness of the present fibrous and porous woods. In softwood with alternating earlywood and latewood layers, the variation in the volume percentage of different layers in a small range has no obvious influence on the mechanical properties of the materials. In contrast, the hardwood presents much higher tensile strength and fracture toughness simultaneously due to its complicated structure with crossed arrangement of the fibers and rays and big vessels diffused in the fibers. The present research findings are expected to provide a fundamental insight into the design of high-performance bionic materials with a highly fibrous and porous structure.

Improving the HCHO Sensing Selectivity on Ag-Doped Graphene by Oxygen Functionalization: A First-Principles Study.

Graphene-based sensors typically fail in the selectivity of target gas detection when exposed to complex and multicompound atmospheres. We have thoroughly compared the adsorptions of various interfering gases (CO, NH3, CH4, C2H2, C2H4, CH3OH, and CH3Cl) with target HCHO on AgG and AgOG by first-principles simulations. The results demonstrate that AgG shows a poor selectivity for HCHO detection and an oxygen functionalized one can improve the selectivity by enhancing the adsorption strength of HCHO and weakening those of other gas molecules. Moreover, the sensing properties of the AgOG sensors are evaluated by the NEGF method, and the predicted HCHO sensing responses are 76 and 32% along the armchair and zigzag directions, respectively. The present work helps shed some light on designing graphene-based sensing materials with high selectivity.

Stress and Defect Effects on Electron Transport Properties at SnO2/Perovskite Interfaces: A First-Principles Insight.

The structural and electronic properties of interfaces play an important role in the stability and functionality of solar cell devices. Experiments indicate that the SnO2/perovskite interfaces always show superior electron transport efficiency and high structural stability even though there exists a larger lattice mismatch. Aiming at solving the puzzles, we have performed density-functional theory calculations to investigate the electronic characteristics of the SnO2/perovskite interfaces with various stresses and defects. The results prove that the PbI2/SnO2 interfaces have better structural stability and superior characteristics for the electron transport. The tensile stress could move the conduction band minimum (CBM) of CH3NH3PbI3 upward, while the compressive stress could move the CBM of SnO2 downward. By taking into account the stress effect, the CBM offset is 0.07 eV at the PbI2/SnO2 interface and 0.28 eV at the MAI/SnO2 interface. Moreover, our calculations classify VI and Ii at the PbI2/SnO2 interface and Sn-I, Ii and Sni at the MAI/SnO2 interface as harmful defects. The Ii defects are the most easily formed harmful defects and should be avoided at both interfaces. The calculated results are in agreement with the available experimental observations. The present work provides a theoretical basis for improving the stability and photovoltaic performance of the perovskite solar cells.

Distinctive Impact of Heat Treatment on the Mechanical Behavior of Nacreous and Crossed-Lamellar Structures in Biological Shells: Critical Role of Organic Matrix.

As biological ceramic composites, mollusk shells exhibit an excellent strength-toughness combination that should be dependent on aragonite/organic matrix interfaces. The mechanical properties and fracture mechanisms of the nacreous structure in the Cristaria plicata (C. plicata) shell and crossed-lamellar structures in the Cymbiola nobilis (C. nobilis) shell were investigated, focusing on the critical role of the organic matrix/aragonite interface bonding that can be adjusted by heat treatments. It is found that heat treatments have a negative impact on the fracture behavior of the nacreous structure in the C. plicata shell, and both the bending and shear properties decrease with increasing heat-treatment temperature because of the loss of water and organic matrix. In contrast, for the crossed-lamellar structure in C. nobilis shell, the water loss in heat treatment slightly decreases its bending properties. When the organic matrix is melted after an appropriate heat treatment at 300°C for 15 min, its bending properties can be greatly enhanced; in this case, remarkable toughening mechanisms involving crack deflection and the fiber pull-out are exhibited, although the interfacial bonding strength reduces. Therefore, an appropriate heat treatment would bring about a positive impact on the fracture behavior of crossed-lamellar structure in the C. nobilis shell. The major research findings have provided an important inspiration that the inducement of moderately weak interfaces rather than all strong interfaces might enhance the comprehensive mechanical properties of fiber-reinforced ceramic composites.

Fyn requires HnRNPA2B1 and Sam68 to synergistically regulate apoptosis in pancreatic cancer.

PURPOSE: The Src family kinase Fyn, heterogenous nuclear ribonucleoprotein (HnRNP) A2B1 and Sam68 are thought to be associated with the metastasis of tumors, but their roles in the regulation of apoptosis remain unclear. This study investigated the role of Fyn and its potential relationship with HnRNPA2B1 and Sam68 in the regulation of apoptosis in pancreatic cancer. Experimental design. We examined both the activity of Fyn and the expression of HnRNPA2B1 in human pancreatic cancer tissues and systematically investigated the apoptotic mechanisms induced by Fyn activity using multiple experimental approaches. RESULTS: We found that Fyn activity was increased in metastatic pancreatic cancer tissues. In the pancreatic cancer BxPc3 cell line, the inhibition of Fyn activity by kinase-dead Fyn downregulated HnRNPA2B1 expression. Further analysis showed that HnRNPA2B1 expression was associated with pancreatic cancer progression. In BxPc3 cells, HnRNPA2B1 bound to Bcl-x messenger RNA (mRNA), which affected splicing and therefore, the formation of Bcl-x(s). Downregulation of HnRNPA2B1 by RNA interference (RNAi) resulted in the increased formation of the pro-apoptotic Bcl-x(s) and promoted apoptosis of BxPc3 cells. In addition, deactivation of Fyn in BxPc3 cells reduced Sam68 phosphorylation. This resulted in increased binding between Sam68 and Bcl-x mRNA, promoting the formation of the anti-apoptotic Bcl-x(L). The knockdown of Sam68 by RNAi also increased the formation of Bcl-x(L). Finally, HnRNPA2B1 overexpression or Sam68 knockdown could rescue pancreatic cancer cells from apoptosis. CONCLUSION: Our results suggest a mechanism by which Fyn requires HnRNPA2B1 and Sam68 to coordinate and regulate apoptosis, thus promoting the proliferation and metastasis of pancreatic cancer.

Diazoxide suppresses hepatic ischemia/reperfusion injury after mouse liver transplantation by a BCL-2-dependent mechanism.

BACKGROUND: Ischemia-reperfusion injury (IRI) is responsible for primary liver dysfunction and failure after transplantation. The mitochondrial pathway appears to be involved in liver ischemia-reperfusion injury. Mitochondrial ATP-sensitive K (mitoK(ATP)) channels play a central role in protecting the heart from injury in ischemic preconditioning. The selective mitoK(ATP) channel agonist diazoxide potently reduced mitochondrial injury by preventing cytochrome c loss from the intermembrane space. Therefore, this study sought to determine whether diazoxide can attenuate ischemia-reperfusion injury induced by orthotopic liver transplantation (OLT) in mice. Furthermore, it was found that up-regulation of the Bcl-2 gene is a mechanism of diazoxide cytoprotection. MATERIALS AND METHODS: Donors were treated with diazoxide, Bcl-2 siRNA, or diazoxide + Bcl-2 siRNA and vehicle 10 min or 24 h before liver harvesting. Liver grafts were then orthotopically transplanted into their corresponding recipients. RESULTS: Liver injury, as judged by transaminase level and histologic examination, was significantly lower in the diazoxide group compared with vehicle controls. The percentage of apoptotic cells and the amount of cytochrome c in the cytosol 6 h after transplant were also markedly reduced in diazoxide-treated grafts compared with vehicle-treated controls. Diazoxide notably up-regulated expression of Bcl-2, while siRNA knockdown of Bcl-2 abolished the cytoprotective effects of diazoxide. CONCLUSIONS: Diazoxide attenuated graft injury after mouse liver transplantation. One mechanism of diazoxide protection involves the induction of Bcl-2, an anti-apoptotic protein. Diazoxide might be useful clinically in hepatic surgery and transplantation.

An Ingenious Microstructure Arrangement in Deep-Sea Nautilus Shell against the Harsh Environment.

Mollusk shells generally consist of several macro-layers with different microstructures. To explore the specific role that different macro-layers play in the overall mechanical properties of shells, the microstructures, hardness distribution, and three-point bending behavior in the deep-sea Nautilus shell were investigated. It is found that the shell presents a hierarchical structure comprising three layers in thickness, that is, the outer, middle, and inner layers, which exhibit homogeneous, prismatic, and nacreous structures, respectively. Among them, the homogeneous structure in the outer layer is harder, which is beneficial for the shell to enhance resistance to wear and perforation. Furthermore, both the bending strength and fracture energy for group Up (loading from outer to inner surfaces) are far higher than those for group Down (loading from inner to outer surfaces), indicating that the inner nacreous layer is not only stronger but also tougher. Cracks tend to deflect at the interfaces in nacreous structure, and nacreous structure is thereby more resistant to breakage. Hence, the nacreous structure in the inner layer could protect the shell from breaking catastrophically in the deep sea with high pressure. In brief, the combination of a harder outside layer and a tougher inside layer provides an effective protective structure for the deep-sea shell, and the excellent environment adaptability of Nautilus shell can thus be interpreted in terms of its ingenious microstructure arrangement.

Roles of Fyn in pancreatic cancer metastasis.

BACKGROUND AND AIMS: Src family kinases have been suggested to be associated with the metastasis of tumors, but their related mechanisms remain unclear. The aims of the present study were to assess the possible mechanisms by which the inhibition of Fyn activation regulates pancreatic cancer metastasis. METHODS: We examined the expressions of Fyn in human pancreatic cancer tissues by immunohistochemistry and systematically investigated the relationship between Fyn expression and pancreatic cancer metastasis. A nude mouse xenograft model induced by BxPC3 cells with or without the inhibition of Fyn activation was used to explore the effect of the inhibition of Fyn on metastasis in vivo. Methyl thiazolyl tetrazolium and terminal deoxynucleotidyl transferase-labeling assays were used to examine the effect of the inhibition of Fyn on the cell proliferation of BxPC3 pancreatic cancer cells in vitro. Reverse transcription polymerase chain reaction and Western blot analysis were performed to explore the possible mechanism of Fyn-induced metastasis. RESULTS: We found that the upregulation of Fyn expression was correlated with human pancreatic cancer metastasis. In BxPC3 pancreatic cancer cells, the inhibition of Fyn activation by kinase-dead Fyn transfection decreased liver metastasis in nude mice. Further analyses showed that Fyn activity modulated pancreatic cell metastasis through the regulation of proliferation and apoptosis. CONCLUSIONS: Our results suggest a possible mechanism by which Fyn activity regulates cell proliferation and apoptosis that exerts an effect on pancreatic cancer metastasis.

The role of MAPK-ERK pathway in 67-kDa laminin receptor-induced FasL expression in human cholangiocarcinoma cells.

BACKGROUND AND AIMS: Cancer cells are thought to possess immune evasion properties due to FasL overexpression in many types of human tumors. In the present study, we set out to investigate the role of MAPK-ERK pathway in 67-kDa laminin receptor induced FasL expression and FasL-mediated apoptosis in human cholangiocarcinoma cells. METHODS: The expression of FasL and its promoter activity in cultured cholangiocarcinoma cells were examined after treatment with laminin or transfection with plasmids containing siRNA targeted to 67-kDa laminin receptor. The effects of MAPK-ERK cascade inhibitor and c-Myc inhibition by siRNA on 67-kDa laminin receptor-induced FasL expression were determined. Apoptosis assay was performed to analyze the apoptosis of lymphocytes cocultured with cholangiocarcinoma cells treated with or without MAPK-ERK cascade inhibitor. RESULTS: Our results revealed that the specific MAPK-ERK cascade inhibitor, PD98059, significantly attenuated phosphorylation of c-Myc on Ser-62 and FasL upregulation in QBC-939 cells and these cells showed decreased cytotoxicity against Fas-sensitive Jurkat T cells. A luciferase reporter assay revealed that FasL promoter activity was significantly reduced in cells treated with PD98059 or transfected with c-Myc siRNA. CONCLUSIONS: Based on these results, we conclude that 67LR induces FasL expression and cytotoxicity against Fas-sensitive Jurkat T cells in human cholangiocarcinoma cells through the phosphorylation of c-Myc on Ser-62 and the subsequent activation of the FasL promoter through the ERK pathway.

[Experimental study of epithelial-mesenchymal transition induced by HBx protein in liver cancer cell].

OBJECTIVE: To explore whether or not HBx protein can induce epithelial-mesenchymal transition (EMT) in liver cancer cell SMMC-7721. METHODS: A recombinant adenovirus vector containing HBx gene was constructed and introduced into SMMC-7721 cell. The morphological changes were observed. The expression changes of epithelial and mesenchymal markers were investigated by RT-PCR, Western blot and immunohistochemistry. Invasive and metastatic capacity of transfected SMMC-7721 cell was evaluated through transwell migration assay. RESULTS: The recombinant adenovirus vector containing HBx gene was constructed and transfected successfully into SMMC-7721 cell. At Day 7 post-transfection, the transfected SMMC-7721 cell underwent the morphological change from a classic epithelial morphology to a spindle-like shape. In addition, the HBx protein significantly increased the expressions of N-cadherin, vimentin and fibronectin, but decreased the expressions of E-cadherin and alpha-catenin in SMMC-7721 cell. The cellular invasion assay indicated that transfection of HBx drastically enhanced the invasive potential of SMMC-7721 cell. CONCLUSION: HBx protein may induce EMT and enhance the invasive potential of SMMC-7721 cell.

HBx protein induces EMT through c-Src activation in SMMC-7721 hepatoma cell line.

The relationships between epithelial-to-mesenchymal transition (EMT), hepatitis B virus X protein (HBx), and the non-receptor tyrosine kinase c-Src were investigated. The HBx gene transfected SMMC-7721 cells underwent morphological changes from a classic epithelial morphology to a spindle-like shape. The HBx transfection increased the invasive potential of these cells. When the transfected cells were exposed to the c-Src kinase inhibitor PP2, the cells recovered their original epithelial morphology and the mRNA and protein expression of epithelial and mesenchymal markers returned to the parental cell levels. Our data suggest that activated c-Src played a critical role in the HBx-induced EMT of SMMC-7721 cells.

[Hepatitis B virus X protein upregulates the transcription activity of zinc finger transcription factor SNAI1].

OBJECTIVE: To investigate whether Hepatitis B virus X protein (HBx) regulates the transcription activity of zinc finger transcription factor SNAI1, and to define the main regulation domain. METHODS: A series of 5' truncated promoters of SNAI1 were amplified and subcloned into the pGL3-Basic vector to construct promoter luciferase report plasmids. The promoter luciferase report plasmids were cotransfected with HBx recombinant adenovirus and pRL-TK plasmid into human hepatocellular cancer cells of the line SMMC7721. Luciferase activity was measured, and relative luciferase activity was calculated. RESULTS: Luciferase reporter plasmids containing 5' flanking deletion of SNAI1 promoter were successfully constructed. HBx obviously upregulated the activity of the SNAI1 promoter (-869 - +59), other than the SNAI1 promoter (-514 - +59) and SNAI1 promoter (-194 - +59). CONCLUSION: HBx can stimulate the transcription of SNAI1, and the transcription regulation domain is located in the segment from -869 - -514 of the SNAI1 promoter.

Metal/Carboxylate-Induced Versatile Structures of Nine 0D → 3D Complexes with Different Fluorescent and Electrochemical Behaviors.

To investigate the effect of the polycarboxylates and metal ions on the assembly and structures of complexes based on a thiophene-containing bis-pyridyl-bis-amide N,N'-bis(pyridine-3-yl)thiophene-2,5-dicarboxamide (3-bptpa) ligand, nine 0D → 3D complexes of [Ni2(3-bptpa)4(1,2-BDC)2(H2O)2] (1), [Ni(3-bptpa)(IP)(H2O)2]·H2O (2), [Ni(3-bptpa)(5-MIP)(H2O)2]·H2O (3), [Ni(3-bptpa)(5-NIP)(H2O)] (4), [Ni(3-bptpa)(5-AIP)]·2H2O (5), [Ni2(OH)(3-bptpa)(1,3,5-BTC)]·DMA·5H2O (6), [Cu(3-bptpa)(5-MIP)]·3H2O (7), [Cu(3-bptpa)(5-AIP)(H2O)0.25]·H2O (8), and [Cu(3-bptpa)(1,3,5-HBTC)] (9) (1,2-H2BDC = 1,2-benzenedicarboxylic acid, H2IP = 1,3-benzenedicarboxylic acid, 5-H2MIP = 5-methylisophthalic acid, 5-H2NIP = 5-nitroisophthalic acid, 5-H2AIP = 5-aminoisophthalic acid, DMA = N,N'-dimethylacetamide, and 1,3,5-H3BTC = 1,3,5-benzenetricarboxylic acid) have been hydrothermally/solvothermally synthesized and structurally characterized by IR, thermogravimetric, powder X-ray diffraction, and single-crystal X-ray diffraction. Complex 1 is a zero-dimensional (0D) bimetallic complex. Complexes 2 and 3 feature two similar one-dimensional ladderlike structures. Complex 4 displays a two-dimensional (2D) 4-connected network based on single-metallic nodes. Complex 5 shows a 2D double-layer structure containing a pair of 63 [Ni(5-AIP)] honeycomblike sheets. Complex 6 is a 3,5-connected three-dimensional (3D) framework derived from bimetallic nodes and 63 [Ni2(OH)(1,3,5-BTC)] honeycomblike sheets. Complex 7 displays a 2D 4-connected grid based on bimetallic nodes. Complex 8 features a 2D double-layer structure based on two 4-connected [Cu(3-bptpa)(5-AIP)] sheets and bridging coordinated water molecules. Complex 9 is a 2D structure extended by incomplete deprotonation of 1,3,5-HBTC and 3-bptpa linkers. The effect of the metal ions and polycarboxylates on the structures of the title complexes was discussed, and the fluorescent properties of 1-9 were investigated. The carbon paste electrodes bulk-modified by complexes 3, 5, and 6-9 show different electrocatalytic activities for the oxidation of ascorbic acid as well as the reduction of hydrogen peroxide, nitrites, and bromates.

[Expression of caveolin-1 gene in hepatitis B-related hepatocellular carcinoma and the clinical significance thereof].

OBJECTIVE: To study the correlation between the expression of caveolin-1 in hepatitis B-related hepatocellular carcinoma (HCC) and the relationship thereof with the invasive and metastatic ability of HCC. METHODS: Real-time PCR and immunohistochemistry were used to detect the expression of caveolin-1 in 123 specimens of HCC tissues obtained during operation. Human HCC cells of the lines MHCC-97L and MHCC-97H were cultured, and Western-blotting was used to detect the caveolin-1 expression in these cells. RESULTS: The expression level of caveolin-1 in the HCC tissues was significantly lower than that of the adjacent noncancerous tissues (P = 0.026). The caveolin-1 mRNA expression in the HBV-related HCC cells was negatively correlated with the tumor size, expression of AFP, major venous invasion, being single or multiple, pTNM staging, and HBx expression level, factors closed to the prognosis of HCC. The caveolin-1 protein expression of the MHCC-97H cells was significantly lower than that of the MHCC-97L cells. CONCLUSION: Caveolin-1 expression is associated with the invasive and metastatic ability of HCC, low expression of caveolin-1 shows poor prognosis of HCC, and caveolin-1 is probably down-regulated by HBx protein.

[Experimental study of relationship of bile composition imbalance with bile duct injury].

OBJECTIVE: To investigate the change of bile composition and its role in bile duct injury after orthotopic liver transplantation (OLT). METHODS: Rats were randomly divided into 3 groups: group A (sham surgery), group B (OLT with 1 h cold preservation), group C (OLT with 12 h cold preservation). The arterialized rat liver transplantation model with biliary extra-drainage was used in group B and C. Animals were sacrificed at posttransplant 1, 3, 5, 7, 10 and 14 day. Routine bile chemistry and pathological assays were performed. RESULTS: Cold preservation/reperfusion injury (CPRI) could repress the secretion of bile salts and phospholipid. However, in contrast with a rapid increase of bile salt secretion, the biliary secretion of phospholipid recovered more slowly, leading to an abnormal high bile salts/phospholipid ratio early after transplantation. Further analysis suggested that the secretion of bile salts correlated strongly with biochemical and histopathological signs of bile duct injury. CONCLUSIONS: CPRI can lead to great changes of graft bile composition, which plays a role in the pathogenesis of bile duct injury following liver transplantation.

Tumor suppressor BLU exerts growth inhibition by blocking ERK signaling and disrupting cell cycle progression through RAS pathway interference.

We have previously reported that the 3p21 tumor suppressor BLU regulates cell cycle by blocking JNK/MAPK signaling. Another member of the MAPK family, extracellular signal response kinase (ERK), is induced by the RAS-RAF-MEK-ERK pathway and is targeted in anticancer therapy. The effects of BLU on tumor growth were evaluated by measuring the size of nasopharyngeal carcinoma (NPC) xenografted tumors intra-tumorally injected with BLU adenovirus 5 (BLU Ad5) and the viability of NPC cells transferred with BLU. Tumor size was correlated with downregulation of the ERK pathway by BLU. Phosphorylation of ERK and Elk reporter activities were assayed. The regulated cyclins D1 and B1 were measured by CCND1 and CCNB1 gene promoter activity by co-transfection of BLU, RAS V12G, together with BLU+RAS V12G, pCD316+RAS V12G. The cell cycle phase distribution was determined by FACS-based DNA content assay. The data showed that growth of the xenografted tumor was inhibited and viability of HONE-1 cells was reduced by recombinant BLU. BLU down-regulated ERK signaling by reducing protein substrate phosphorylation, inhibiting Elk reporter activity, and blocking promoter activities of the CCND1 gene and reduced cyclins D1 expression to arrest the cell cycle at the G1 phase. The population of G2/M cells was also remarkably decreased. HRAS V12G activated ERK and cyclin D1 and B1 promoters, and the effects were antagonized by BLU. Taken together, our results suggested that BLU inhibited ERK signaling, downregulated cyclins D1 and B1, and prevented cell cycle progression through interfering with HRAS V12G signaling to exert tumor suppression.

[Effect of cold preservation and reperfusion injury on early-stage bile salt secretion after liver transplantation in rat model].

OBJECTIVE: To explore the effect of cold preservation and reperfusion injury (CPRI) on the bile salt spectrum in rat orthotopic liver transplantation (OLT) model. METHODS: A special analysis method was established to investigate the bile salts in rat by reverse phase high performance liquid chromatography (RP-HPLC). Rats were randomly divided into 3 groups: group A (control group, n = 6), group B (group with 1 h graft preservation pre-OLT, n = 6) and group C (group with 12 h graft preservation pre-OLT, n = 6). The bile samples of 0 - 14 post-transplantation days were analyzed by RP-HPLC. RESULTS: Eleven kinds of bile salts were detected in rat bile. It showed that CPRI could influence the concentration of bile salts significantly in rat model after OLT, the concentration of hydrophobic bile salts (TCA and TCDCA) increased significantly in group B and C. However, the concentration of hydrophilic bile salts (TUDCA and THDCA) just increased in a short-time. The hydrophobicity index (HI) wasn't significantly changed during the first 4 post-transplant days. Thus the HI of bile salts elevated gradually from the 5th day and reached the peak at the 10th day after OLT. CONCLUSION: The increase of the proportion of hydrophobic bile salts may be one of the major factors leading to the increase of bile toxicity after OLT.