PD-L1/PD-1 blockage enhanced the cytotoxicity of natural killer cell on the non-small cell lung cancer (NSCLC) by granzyme B secretion.

OBJECTIVE: To explore the role of PD-L1/PD-1 blockage in the cytotoxicity of natural killer cell in NSCLC. METHODS: Two NSCLC cell lines, Calu-1 and H460, were tested for susceptibility to the cytolytic activity of freshly isolated healthy donor NK cells by a non-radioactive cellular cytotoxicity assay kit. Western blot analysis, FACS, ELISA and antibody blockage experiments were conducted to determine the mechanisms. NK cells isolated from NSCLC patients were also collected for functional assays. RESULTS: Calu-1 and H460 cells were lysed by NK cells in a dose-dependent manner. H460 cells showed less susceptibility to NK cell-mediated lysis than Calu-1 cells at all ratios. The expression of PD-L1 on H460 cells was higher than that on Calu-1 cells, as determined by FACS and western blot analysis. The specific lysis of H460 cells by NK cells was enhanced when the PD-L1/PD-1 interaction was blocked by anti-PD-L1 antibody. This finding was also demonstrated in NK cells isolated from NSCLC patients. CONCLUSIONS: The present study revealed that PD-L1/PD-1 blockage enhanced the cytotoxicity of natural killer cells in NSCLC via granzyme B secretion. This study will greatly facilitate the precise treatment of lung cancer through determination of PD-L1 expression in tumors.

Antimicrobial mexicanolide limonoids from the seeds of Khaya senegalensis.

Three new mexicanolide limonoids were obtained from the 90% ethanol extract of the seeds of Khaya senegalensis. Their structures were elucidated as senegalenines A-C (1-3) by analysing their 1D/2D NMR and MS spectroscopic analysis. In addition, the isolated limonoids were tested in vitro for antimicrobial potentials against 5 pathogenic microorganisms. Consequently, compounds 1-3 exhibited antimicrobial activity against the tested Gram negative bacteria at the minimum inhibitory concentration values less than 40 µg/ml.

Role of hyaluronic acid and laminin as serum markers for predicting significant fibrosis in patients with chronic hepatitis B.

OBJECTIVES: The aim of this study was to evaluate the diagnostic performance of serum HA and LN as serum markers for predicting significant fibrosis in CHB patients. METHODS: Serum HA and LN levels of 87 patients with chronic hepatitis B and 19 blood donors were assayed by RIA. Liver fibrosis stages were determined according to the Metavir scoring-system. The diagnostic performances of all indexes were evaluated by the receiver operating characteristic (ROC) curves. RESULTS: Serum HA and LN concentrations increased significantly with the stage of hepatic fibrosis, which showed positive correlation with the stages of liver fibrosis (HA: r = 0.875, p < 0.001; LN: r = 0.610, p < 0.001). There were significant differences of serum HA and LN levels between F2-4 group in comparison with those in F0-F1 group (p < 0.001) and controls (p < 0.001), respectively. From ROC curves, 185.3 ng/mL as the optimal cut-off value of serum HA for diagnosis of significant fibrosis, giving its sensitivity, specificity, PPV, NPV, LR+, LR- and AC of 84.2%, 83.3%, 90.6%, 73.5%, 5.04, 0.19 and 83.9, respectively. While 132.7 ng/mL was the optimal cut-off value of serum LN, the sensitivity, specificity, PPV, NPV, LR+, LR- and AC were 71.9%, 80.0%, 87.2%, 60.0%, 3.59%, 0.35% and 74.7, respectively. Combinations of HA and LN by serial tests showed a perfect specificity and PPV of 100%, at the same time sensitivity declined to 63.2% and LR+ increased to 18.9, while parallel tests revealed a good sensitivity of 94.7%, NPV to 86.4%, and LR- declined to 0.08. CONCLUSIONS: Serum HA and LN concentrations showed positive correlation with the stages of liver fibrosis. Detection of serum HA and LN in predicting significant fibrosis showed good diagnostic performance, which would be further optimized by combination of the two indices. HA and LN would be clinically useful serum markers for predicting significant fibrosis in patients with chronic hepatitis B, when liver biopsy is contraindicated.

Role of hyaluronic acid and laminin as serum markers for predicting significant fibrosis in patients with chronic hepatitis B

OBJECTIVES: The aim of this study was to evaluate the diagnostic performance of serum HA and LN as serum markers for predicting significant fibrosis in CHB patients. METHODS: Serum HA and LN levels of 87 patients with chronic hepatitis B and 19 blood donors were assayed by RIA. Liver fibrosis stages were determined according to the Metavir scoring-system. The diagnostic performances of all indexes were evaluated by the receiver operating characteristic (ROC) curves. RESULTS: Serum HA and LN concentrations increased significantly with the stage of hepatic fibrosis, which showed positive correlation with the stages of liver fibrosis (HA: r = 0.875, p < 0.001; LN: r = 0.610, p < 0.001). There were significant differences of serum HA and LN levels between F2-4 group in comparison with those in F0-F1 group (p < 0.001) and controls (p < 0.001), respectively. From ROC curves, 185.3 ng/mL as the optimal cut-off value of serum HA for diagnosis of significant fibrosis, giving its sensitivity, specificity, PPV, NPV, LR+, LR- and AC of 84.2 percent, 83.3 percent, 90.6 percent, 73.5 percent, 5.04, 0.19 and 83.9, respectively. While 132.7 ng/mL was the optimal cut-off value of serum LN, the sensitivity, specificity, PPV, NPV, LR+, LR- and AC were 71.9 percent, 80.0 percent, 87.2 percent, 60.0 percent, 3.59 percent, 0.35 percent and 74.7, respectively. Combinations of HA and LN by serial tests showed a perfect specificity and PPV of 100 percent, at the same time sensitivity declined to 63.2 percent and LR+ increased to 18.9, while parallel tests revealed a good sensitivity of 94.7 percent, NPV to 86.4 percent, and LR- declined to 0.08. CONCLUSIONS: Serum HA and LN concentrations showed positive correlation with the stages of liver fibrosis. Detection of serum HA and LN in predicting significant fibrosis showed good diagnostic performance, which would be further optimized by combination of the two indices. HA and LN would be clinically useful serum markers for predicting significant fibrosis in patients with chronic hepatitis B, when liver biopsy is contraindicated.

Diagnostic accuracy of a specific cytokine pattern in hemophagocytic lymphohistiocytosis in children.

OBJECTIVE: The study goal was to determine the diagnostic accuracy of a specific cytokine pattern including interferon-gamma (IFN-γ), interleukin (IL)-10, and IL-6 for hemophagocytic lymphohistiocytosis (HLH) in febrile children. STUDY DESIGN: In this prospective study, 756 patients with fever admitted to a hematology-oncology unit were enrolled. The causes of fever were documented and the serum cytokines, including IFN-γ, tumor necrosis factor-alpha (TNF-α), IL-10, IL-6, IL-4, and IL-2, were determined using cytometric bead array techniques. RESULTS: Of 1474 episodes of fever that were analyzed, 71 episodes of HLH manifested a specific cytokine pattern of highly increased levels of IFN-γ (median level: 1088.5 pg/mL) and IL-10 (623.5 pg/mL) but a moderately increased level of IL-6 (51.1 pg/mL). IL-6 was predominantly increased to varied extents in patients in the sepsis group (244.6 pg/mL) and the nonsepsis infection group (34.7 pg/mL). The diagnostic accuracy of IFN-γ and IL-10 for HLH was 99.5% and 92.8%, respectively. By applying the cutoff point of 100 pg/mL, IFN-γ had a sensitivity of 94.4% and a specificity of 97.2% for HLH. When using the criteria of IFN-γ >75 pg/mL and IL-10 >60 pg/mL, the specificity reached 98.9% and the sensitivity was 93.0%. CONCLUSIONS: The specific cytokine pattern of markedly elevated levels of IFN-γ and IL-10 with only modestly elevated IL-6 levels has high diagnostic accuracy for HLH and may be a useful approach to differentiate HLH from infection.