IL-8-induced CXCR2 down-regulation in circulating monocytes in hepatocellular carcinoma is partially dependent on MAGL.

BACKGROUND: CXC-chemokine receptor 2 (CXCR2) expression was found to be down-regulated on circulating monocytes of cancer patients. Here, we analyze the percentage of CD14+CXCR2+ monocyte subsets in hepatocellular carcinoma (HCC) patients, and investigate the mechanisms that regulate CXCR2 surface expression on monocytes and its biological function. METHODS: Flow cytometry was used to analyze the proportion of the CD14+CXCR2+ subset from the total circulating monocytes of HCC patients. Interleukin 8 (IL-8) levels were measured from serum and ascites, and their correlation with the CD14+CXCR2+ monocyte subset proportion was calculated. THP-1 cells were cultured in vitro and treated with recombinant human IL-8 and CXCR2 surface expression was analyzed. CXCR2 was knocked down to examine how it affects the antitumor activity of monocytes. Finally, a monoacylglycerol lipase (MAGL) inhibitor was added to analyze its effect on CXCR2 expression. RESULTS: A decrease in the proportion of the CD14+CXCR2+ monocyte subset was observed in HCC patients compared with healthy controls. CXCR2+ monocyte subset proportion was associated with the AFP value, TNM stage, and liver function. Overexpression of IL-8 was observed in the serum and ascites of HCC patients, and negatively correlated with CXCR2+ monocyte proportion. IL-8 decreased CXCR2 expression in THP-1 cells, contributing to decreased antitumor activity toward HCC cells. MAGL expression in THP-1 cells was up-regulated after IL-8 treatment, and the MAGL inhibitor partially reversed the effects of IL-8 on CXCR2 expression. CONCLUSIONS: Overexpression of IL-8 drives CXCR2 down-regulation on circulating monocytes of HCC patients, which could be partially reversed by a MAGL inhibitor.

[The Clinical Significance of Tumor-associated Antigens in Dermatomyositis Patients with Interstitial Lung Disease].

OBJECTIVE: To investigate the relationship between tumor related markers and the presence of interstitial lung disease (ILD) in dermatomyositis (DM) patients as well as potential serum markers for accompanied ILD. METHODS: Fifty-nine DM patients were included,including 30 patents with ILD. Serum level of anti-transcription intermediary factor1-γ (TIF1-γ) and tumor-associated antigens (TAAs) were detected to analyze the correlation of these markers with ILD. Meanwhile,the diagnostic value of these markers was evaluated by receive operating characteristic (ROC) curve analysis. RESULTS: We found that there were 5 patients bearing malignancies,independent from the presence of ILD (P=0.024). Serum anti-TIF1-γ was positive in 4/5 DM patients with tumor,of which sensitivity and specificity were 36.36% and 97.92%,respectively. In contrast,only one case was found positive anti-TIF1-γ in 30 DM with ILD (P=0.002).Carbohydrate antigen (CA)125,CA153,and cytokeratin-19 fragment (CYFRA21-1) were elevated in DM patients with ILD in compared to those without ILD. The area under curve (AUC) of CYFRA21-1 for the prediction of ILD was 0.745 (P=0.002). The optimal cut-off value was 3.58 ng/mL with a sensitivity of 60.71% and a specificity of 84.00%. The AUC in combination of CA125 and CYFRA21-1 could reach 0.801 (P<0.002) with a sensitivity of 64.29% and a specificity of 82.61%. CONCLUSION: Presence of malignance and positive anti-TIF1γ could be the protective factors for ILD in DM. Elevated serum levels of CA125,CA153,CYFRA21-1 could indicate the accompanying ILD.

Effect of low-dose tacrolimus with mycophenolate mofetil on renal function following liver transplantation.

AIM: To determine whether low-dose tacrolimus (TAC) combined with mycophenolate mofetil (MMF) is a safe approach to decrease the incidence of chronic kidney disease (CKD) in liver transplantation (LT) recipients. METHODS: We analyzed the medical records of 689 patients who underwent LT between March 1999 and December 2012 in a single Chinese center. Immunosuppression was initiated with a calcineurin inhibitor (TAC or CSA) and prednisone with or without MMF. CKD is defined by the glomerular filtration rate (GFR), estimated by an abbreviated Modification of Diet in Renal Disease formula, < 60 mL/min per 1.73 m(2) for at least 3 consecutive months after LT. Individuals with TAC trough concentrations ≤ 8 ng/mL at 3 mo after LT were defined as the low-dose group. The incidence of CKD within 5 years was compared between the TAC group and the CSA group, as well as between four subgroups (low-dose and high-dose TAC groups with or without MMF). RESULTS: No difference regarding the occurrence of pre-LT renal dysfunction or that of post-LT rejection was found between the TAC and CSA groups or between the four subgroups. With a definition of GFR < 60 mL/min per 1.73 m(2), the overall incidence of CKD was significantly higher in the CSA group than in the TAC group. The incidence of CKD in the low-dose TAC + MMF group (7.7%) was significantly lower than that observed in the low-dose TAC group (15.9%), high-dose TAC group (24.6%) and high-dose TAC + MMF group (18.5%). The cumulative 1-, 3- and 5-year incidence rates of CKD were 12.7%, 14.5% and 16.7%, respectively. The cumulative 5-year survival rates were 61.7% and 82.2% in patients with or without CKD, respectively. CONCLUSION: In LT patients, the choice of immunosuppressive therapy appears to affect renal function and patient survival.

Fabrication of block copolymer brushes on hollow sphere surface via reverse iodine transfer polymerization.

The block copolymer brushes grafted from hollow sphere surface via reverse iodine transfer polymerization (RITP) were investigated in this work. A sufficient amount of azo initiator was introduced onto hollow sphere surface firstly. Then the monomer methyl methacrylate (MMA) was polymerized via surface-initiated reverse iodine transfer polymerization (RITP) using azo group modified hollow sphere as initiator. The microstructure of the samples was characterized by FT-IR, (1)H NMR, respectively. Results indicated that the poly(methyl methacrylate) (PMMA) with end functionality of alkyl iodine group had grafted from hollow sphere surface. TEM observations showed that the average diameter of hollow core was central at 1.3-1.4 µm and the average wall thickness increased from 103 nm to 138 nm and 172 nm after grafting polymerization of MMA and Tb complex, respectively. The closely linear plots of molecular weight (M(n)) versus conversion, linear kinetic plots for the free polymer formed in solution and the ability to extend the chains by sequential addition of monomer indicated that the RITP was a controlled process with a "living" characteristic.

Mineralization mechanism of calcium phosphates under three kinds of Langmuir monolayers.

Three kinds of Langmuir monolayers formed by dipalmitoylphosphatidylcholine (DPPC), arachidic acid (AA), and octadecylamine (ODA) were used as templates to study the initial stage of nucleation and crystallization of calcium phosphates. It was demonstrated that the combination of calcium ions (or phosphates) to the monolayer/subphase interface is a prerequisite for subsequent nucleation. It was found that calcium phosphate dihydrate (DPCD) formed at 25.0 degrees C for 12 h has a biphasic structure containing both amorphous and crystalline phases. These results showed that calcium phosphates were formed through a multistage assembly process, during which an initial amorphous phase DPCD was followed by a phase transformation into a crystalline phase and then the most stable hydroxyapatite (HAp). This provided new insights into the template-biomineral interaction and a mechanism for biomineralization.