Targeting MUC1 and JNK by RNA interference and inhibitor inhibit the development of hepatocellular carcinoma.

Mucin 1 (MUC1), as an oncogene, is overexpressed in hepatocellular carcinoma (HCC) cells and promotes the progression and tumorigenesis of HCC through JNK/TGF-ß signaling pathway. In the present study, RNA interference (RNAi) and JNK inhibitor SP600125, which target MUC1 and/or JNK, were used to treat HCC cells in vitro, and the results showed that both silencing the expression of MUC1 and blocking the activity of JNK inhibited the proliferation of HCC cells. In addition, MUC1-stable-knockdown and SP600125 significantly inhibited the growth of tumors in the subcutaneous transplant tumor models that established in BALB/c nude mice rather than MUC1 or JNK siRNAs transiently transfection. Furthermore, the results from immunohistochemical staining assays showed that the inhibitory effects of MUC1 gene silencing and SP600125 on the proliferation of HCC cells in vivo were through the JNK/TGF-ß signaling pathway. These results indicate that MUC1 and JNK are attractive targets for HCC therapy and may provide new therapeutic strategies for the treatment of HCC.

Escherichia coli Maltose-Binding Protein Induces M1 Polarity of RAW264.7 Macrophage Cells via a TLR2- and TLR4-Dependent Manner.

Maltose-binding protein (MBP) is a critical player of the maltose/maltodextrin transport system in Escherichia coli. Our previous studies have revealed that MBP nonspecifically induces T helper type 1 (Th1) cell activation and activates peritoneal macrophages obtained from mouse. In the present study, we reported a direct stimulatory effect of MBP on RAW264.7 cells, a murine macrophage cell line. When stimulated with MBP, the production of nitric oxide (NO), IL-1ß, IL-6 and IL-12p70, and the expressions of CD80, MHC class II and inducible nitric oxide synthase (iNOS) were all increased in RAW264.7 cells, indicating the activation and polarization of RAW264.7 cells into M1 macrophages induced by MBP. Further study showed that MBP stimulation upregulated the expression of TLR2 and TLR4 on RAW264.7 cells, which was accompanied by subsequent phosphorylation of IκB-α and p38 MAPK. Pretreatment with anti-TLR2 or anti-TLR4 antibodies largely inhibited the phosphorylation of IκB-α and p38 MAPK, and greatly reduced MBP-induced NO and IL-12p70 production, suggesting that the MBP-induced macrophage activation and polarization were mediated by TLR2 and TLR4 signaling pathways. The observed results were independent of lipopolysaccharide contamination. Our study provides a new insight into a mechanism by which MBP enhances immune responses and warrants the potential application of MBP as an immune adjuvant in immune therapies.

catena-Poly[[tetra-aqua-manganese(II)]-µ-5-carboxyl-ato-1-carboxyl-atomethyl-2-oxidopyridinium-κO:O].

In the title coordination polymer, [Mn(C(8)H(5)NO(5))(H(2)O)(4)](n), the Mn(II) atom is coordinated by two carboxyl-ate O atoms from two 5-carboxyl-ato-1-carboxyl-atomethyl-2-oxidopyridinium (L(2-)) ligands and by four water mol-ecules in a distorted octa-hedral geometry. The L(2-) ligands bridge the Mn atoms into an infinite chain motif along [100]; the chains are further inter-linked by O-H⋯O hydrogen bonds into a three-dimensional supra-molecular net.

[Reproduction of a rat model of disseminated intravascular coagulation accompanied by multiple organ injuries].

OBJECTIVE: To reproduce a rat model of disseminated intravascular coagulation (DIC) accompanied by multiple organ dysfunction syndrome (MODS) induced by endotoxin. METHODS: Twenty-four healthy Wistar rats were randomly divided into four groups: control group, low dosage lipopolysaccharide (LPS) group, middle dosage LPS group, and high dosage LPS group (each n=6). Rats of each group were given different dosages of normal saline (1.4 ml/kg, 2.8 ml/kg), low dosages LPS [1.4 mg/kg (56 microg/kg), 2.8 ml/kg (112 microg/kg)], middle dosages LPS [1.4 mg/kg(98 microg/kg), 2.8 ml/kg (196 microg/kg)] and high dosages LPS [1.4 ml/kg (196 microg/kg), 2.8 ml/kg (392 microg/kg)] respectively twice 12 hours apart through femoral vein intubation injection. Blood platelet (PLT) count, coagulation function, D-dimer, fibrinogen (Fbg), antithrombin III (AT-III) blood glucose (Glu), biochemistry indexes including aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were determined before and after LPS challenge, and histopathologic changes of lung, liver and kidney were observed 4 hours after the second injection. RESULTS: The rats in high dosage LPS group died 4 hours later, and the rats in low and middle dosage LPS groups survived after double LPS challenge. The results of blood PLT, D-dimer, Fbg, Glu, AST, ALT, ALP, LDH, coagulation function of activated partial thromboplastin time, prothrombin time and level of anti-thrombin III in middle dosage LPS group were significantly different compared with those of control group (P<0.05 or P<0.01). Obvious changes in histopathology were found in major organs such as lung, kidney and liver. CONCLUSION: Double intravenous LPS challenge (98 microg/kg and 196 microg/kg) in rats can reproduce a rat model with DIC accompanied by multiple organ injuries.

Exploring the mechanism of WWOX growth inhibitory effects on oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most common types of head and neck neoplasms in the world. Patients diagnosed with OSCC exhibit a poor prognosis. WW domain-containing oxidoreductase (WWOX), as a candidate tumor-suppressor gene, is involved in the genesis and progression of tumors. The deletion of the WWOX gene has been identified in OSCC and oral leukoplakia, but the function and mechanism of WWOX in OSCC remain unknown. Therefore, the present study investigated the role of WWOX in oral squamous carcinoma cells. The results revealed that an elevation of WWOX expression had an inhibitory effect on the growth of three types of oral squamous carcinoma cells, with the most evident effect occurring in Tca8113 cells. Also, in the Tca8113 cells, WWOX overexpression significantly inhibited colony formation, and induced apoptosis and cell cycle arrest. Microarray analysis, reverse transcription-quantitative polymerase chain reaction and western blotting methods detected that WWOX overexpression contributed to the differential expression of the genes involved in mediating the extracellular-signal regulated protein kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway. These results suggest that the tumor-suppressor function of the WWOX gene may be associated with the modulation of the ERK/MAPK signaling pathway, thus providing a novel target for OSCC therapy.

[Characteristics of Pb2+ and Cd2+ sorption in aqueous solution by wheat straw].

Wheat straw was used as biosorbent for lead and cadmium removal from aqueous solution. Especially, the effect of solution pH, contact time and ions concentration on the sorption process was intensively discussed. Result indicated that the metal removal was strongly dependent on solution pH and the sorption capacity increased with the increasing of solution pH in the pH range of 2.0-6.0. The sorption kinetic process fit well with the pseudo-second-order. Langmuir isotherm equation was used to evaluate the sorption capacity of the biomass. The q(max) values for Pb2+ and Cd2+ were 0.15 mmol x g(-1) and 0.11 mmol x g(-1) respectively. After NaOH hydrolated, wheat straw showed higher sorption capacity both for Pb2+ and Cd2+, q(max) values for Pb2+ and Cd2+ reached 0.31 and 0.22 mmol x g(-1) respectively. While the sorption capacity for Pb2+ and Cd2+ on esterified wheat straw decreased greatly. Fourier transform infrared spectroscopy (FTIR) analysis showed that carboxylic groups on the biomass play an important role in Pb2+ and Cd2+ sorption process.