Interleukin (IL)-7 plays a vital role in proliferation and activation of T cells, however, its signaling through CD127 is impaired in T cells in cancers and chronic infections. The mechanisms underlying T helper 17 (Th17) cell responses by IL-7 in melanoma remain not fully understood. The aim of this study was to assess the effect of IL-7 signaling on Th17 responses in patients with primary cutaneous melanoma. Healthy and primary cutaneous melanoma donors were selected for this study of Th17 cell function. IL-17 + CD4 + Th17 cells and CD127 expression on Th17 cells were determined by flow cytometry. Cytokine level was measured by ELISA. Peripheral and tissueinfiltrating CD4 + T cells were isolated using magnetic beads, and then stimulated with IL-7 and/or signal transducer and activator of transcription 5 inhibitor. Activated signaling molecules were analyzed by flow cytometry. Peripheral and tumor-infiltrating Th17 cells percentage was decreased, while peripheral IL-7 level was also reduced in melanoma patients. There was no significant difference of CD127 expression on Th17 cells between melanoma patients and controls. Antiapoptotic protein Bcl-2 was downregulated, whereas proapoptotic protein-activated caspase-3 was upregulated in peripheral and tissue-infiltrating Th17 cells in melanoma patients.Higher concentration of IL-7 (10 ng/mL), but not lower IL-7 concentration (1 ng/mL), promoted Bcl-2 expression and decreased caspase-3 expression in Th17 cells in melanoma patients. Inhibition of signal transducer and activator of transcription 5 resulted in the downregulation of Bcl-2 while upregulation of caspase-3 in Th17 cells. The present data suggested that reduced IL-7 responsiveness might be insufficient for Th17 activation in patients with primary cutaneous melanoma.
Aim. Transjugular intrahepatic portosystemic shunt (TIPS) alters the liver blood supply and reduces portal pressure. This study was to investigate the changes and associations of the hepatic blood flow, liver volume, and portal pressure gradient (PPG) after TIPS in liver cirrhosis. Methods. Twenty-one patients with liver cirrhosis who received TIPS were recruited. The contrast CT images were used to assess the iodine density (ID) of liver parenchymal and liver volume. The ID of the liver parenchyma was used to reflect hepatic blood flow. We used a paired t-test and regression analysis to investigate the effect of TIPS on hepatic blood flow, liver volume, and PPG in individuals with cirrhosis and the factors that affect changes in liver volume. Results. After TIPS, there was a significant improvement in the ID of liver parenchyma at arterial phase (AP) and PPG in individuals with cirrhosis ( P < 0.05). Each 1 unit increase in the ID change of whole liver parenchyma at the venous phase (VP) was significantly associated with a 269.44 cm3 increase in the liver volume after TIPS (b = 269.44, P = 0.012). With an increasing ID change of whole liver parenchyma at VP, the change in liver volume followed an increasing trend ( P for overall association = 0.005). Conclusions. Our data indicate that there was a significant improvement in hepatic blood flow, especially at AP, after TIPS and the change in hepatic blood supply from the portal vein is positively associated with the change in liver volume after TIPS. Increasing the blood supply to the liver from the portal vein may improve the reduction of liver volume.
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