Three new lignanamides from the root of <i>Lycium chinense</i> with anti-inflammatory activity

<p>Three new lignanamides, that is, a new lignanamide (<b>1</b>), and a pair of enantiomers (<b>2a</b> and <b>2b</b>) were isolated from the EtOAc-soluble fraction of an EtOH extract of the root of <i>Lycium chinense</i>. The structures of these new compounds, including their absolute configuration, were established on the basis of HR-ESI-MS, NMR spectroscopic data and quantum chemical ECD calculations. Compound <b>2a</b> showed significant anti-inflammatory activity in LPS-induced RAW 264.7 macrophages with the IC₅₀ value of 10.77 ± 2.14 μM, comparing to that of positive control quercetin (17.21 ± 0.50 μM).</p

Ceruloplasmin Is a Potential Biomarker for aGvHD following Allogeneic Hematopoietic Stem Cell Transplantation

<div><p>Acute graft-versus-host-disease (aGvHD) is the major cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recently, diagnostic biomarkers for aGvHD have been shown to play important roles in evaluating disease status and mortality risk after allo-HSCT. To identify plasma biomarkers for aGvHD with high sensitivity and specificity, a quantitative proteomic approach using 8-plex isobaric tags for relative and absolute quantitation (8-plex iTRAQ) was employed to screen differentially expressed proteins in peripheral blood before and after the onset of aGvHD. Four target proteins, ceruloplasmin (CP), myeloperoxidase (MPO), complement factor H (CFH), and alpha-1-acid glycoprotein (AGP), were chosen for preliminary validation with enzyme linked immunosorbent assay (ELISA) in 20 paired samples at both the time of diagnosis of aGvHD and the time of complete response. The most promising candidate, ceruloplasmin, was further validated at fixed time points after allo-HSCT and during aGvHD. The plasma ceruloplasmin levels were significantly increased during the period of aGvHD onset and were markedly decreased as aGvHD resolved. The plasma ceruloplasmin levels at different time points post-transplant in the aGvHD (+) group were significantly higher than those in the aGvHD (−) group (p<0.001). The elevation of ceruloplasmin level in patients with active aGvHD was independent of infection status. Patients whose ceruloplasmin levels were elevated above 670 μg/ml at 7, 14 and 21 days after allo-HSCT had a remarkably increased probability of subsequently developing aGvHD. In conclusion, our results suggest that plasma ceruloplasmin is a potential plasma biomarker of aGvHD, and it also has prognostic value for risk-adapted prophylaxis during the consecutive time points monitored in the first month after allo-HSCT.</p> </div

A new lignan from the roots of <i>Syringa pinnatifolia</i>

<div><p>Phytochemical investigation of the roots of <i>Syringa pinnatifolia</i> has resulted in the isolation of a new lignan, pinnatifolin A (<b>1</b>), together with seven known compounds (<b>2</b>–<b>8</b>). The structures were elucidated on the basis of extensive spectroscopic methods, including NMR, MS, UV and IR spectra. The seven lignans were screened for their antioxidant activity (DPPH assay), and most of them showed potent antioxidant activity.</p></div

Comparison of ceruloplasmin levels in infection and aGvHD.

<p>Infection+aGvHD- (n = 18; systemic n = 11; symptomatic n = 7) and aGvHD+infection- (n = 37; systemic n = 16; symptomatic n = 21) were compared at diagnosis of complications as well as recovery.</p

Data_Sheet_1_ABCC9 Is Downregulated and Prone to Microsatellite Instability on ABCC9tetra in Canine Breast Cancer.doc

Tumorigenesis is associated with metabolic abnormalities and genomic instability. Microsatellite mutations, including microsatellite instability (MSI) and loss of heterozygosity (LOH), are associated with the functional impairment of some tumor-related genes. To investigate the role of MSI and LOH in sporadic breast tumors in canines, 22 tumors DNA samples and their adjacent normal tissues were evaluated using polyacrylamide gel electrophoresis and silver staining for 58 microsatellites. Quantitative real-time polymerase chain reaction, promoter methylation analysis and immunohistochemical staining were used to quantify gene expression. The results revealed that a total of 14 tumors (6 benign tumors and 8 breast cancers) exhibited instability as MSI-Low tumors. Most of the microsatellite loci possessed a single occurrence of mutations. The maximum number of MSI mutations on loci was observed in tumors with a lower degree of differentiation. Among the unstable markers, FH2060 (4/22), ABCC9tetra (4/22) and SCN11A (6/22) were high-frequency mutation sites, whereas FH2060 was a high-frequency LOH site (4/22). The ABCC9tetra locus was mutated only in cancerous tissue, although it was excluded by transcription. The corresponding genes and proteins were significantly downregulated in malignant tissues, particularly in tumors with MSI. Furthermore, the promoter methylation results of the adenosine triphosphate binding cassette subfamily C member 9 (ABCC9) showed that there was a high level of methylation in breast tissues, but only one case showed a significant elevation compared with the control. In conclusion, MSI-Low or MSI-Stable is characteristic of most sporadic mammary tumors. Genes associated with tumorigenesis are more likely to develop MSI. ABCC9 protein and transcription abnormalities may be associated with ABCC9tetra instability.</p

Ceruloplasmin levels in different types of aGvHD.

<p>Comparison of ceruloplasmin level in patients with different aGvHD involved organs: Skin (n = 40), Gastrointestinal (GI, n = 11) and Mixed (Skin & GI, n = 21).</p

Preliminary validation of four candidate proteins.

<p>Four candidate proteins underwent preliminary validation were tested by ELISA in paired samples from 20 patients at active aGvHD onset and after complete response(CR). (A) Ceruloplasmin (CP) (Diagnosis Vs. CR p<0.001), (B) alpha-1-acid glycoprotein (AGP) (Diagnosis Vs. CR p = 0.031), (C) Complement factor H (CFH) (Diagnosis Vs. CR p  = 0.052), (D) Myeloperoxidase (MPO) (Diagnosis Vs. CR p = 0.073).</p

ROC analysis of ceruloplasmin levels at aGvHD diagnosis.

<p>(ROC) curve analysis of patients with aGvHD (n = 72) and without aGvHD (n = 26). At a cutoff value of 780 μg/ml, the corresponding sensitivity was 0.905, the specificity was 0.8, the area under the ROC was 0.902 (95% CI 0.825, 0.979; P<0.001), and the standard error was 0.039.</p

The cumulative incidence of aGvHD at multiple time points.

<p>Comparison of cumulative incidence of aGvHD in two groups of patients (CP> 670 μg/ml or <670 μg/ml) at different time points: d+7(p = 0.014), d+14(p<0.001), d+21(p<0.001) and d+28(p = 0.073).</p

Effects of lentivirus-mediated ADAM17 RNAi on the expression of MMP9 and p-p65 protein, and the phosphorylation of IκBα, in response to LPS.

<p>(A)The silencing effects of lentivirus mediated RNA interference on ADAM17 expression in A549 cells. (B) The effects of lentiviral ADAM17 RNA interference on LPS-induced TNF-α protein production in the supernatants. A549 cells were infected for 72 h with LV-ADAM17-shRNA or LV-NC-shRNA and then stimulated for 24 h with LPS (100 µg/l). (C) The effects of lentiviral ADAM17 RNA interference on TNF-α shedding in A549 cells. The level of TNF-α in the A549 cells was detected by western blotting. (D) The effects of lentiviral ADAM17 RNA interference on LPS-induced expression of MMP9 mRNA. Lane 1: DNA ladder marker; lane 2: the group not stimulated with LPS; lane 3: A549 cells stimulated for 24 h with LPS (100 µg/l); lane 4: A549 cells were infected for 72 h with LV-NC-shRNA and then stimulated for 24 h with LPS (100 µg/l); lane 5: A549 cells were infected for 72 h with LV-ADAM17-shRNA and then stimulated for 24 h with LPS (100 µg/l). (E) The effects of lentiviral ADAM17 RNA interference on LPS-induced expression of MMP9 protein. A549 cells were infected for 72 h with LV-ADAM17-shRNA or LV-NC-shRNA and then stimulated for 24 h with LPS at a concentration of 100 µg/l. (F) The effects of lentiviral ADAM17 RNA interference on LPS-induced phosphorylation of IκBα and p65. A549 cells were infected for 72 h with LV-ADAM17-shRNA or LV-NC-shRNA and then stimulated for 24 h with LPS at a concentration of 100 µg/l. Both the phosphorylation of IκBα and p65 was detected via western blotting. (G) The effects of lentiviral ADAM17 RNA interference on IκBα protein expression in the cytoplasm. A549 cells were infected for 72 h with LV-ADAM17-shRNA or LV-NC-shRNA and then stimulated for 24 h with LPS at a concentration of 100 µg/l. The level of IκBα in the cytoplasm was detected via western blotting.</p