Exploration the Immune Regulatory Mechanism of Hedysari Radix Based on Network Pharmacology,Molecular Dynamics,and UPLC-MS/MS / 中药新药与临床药理

Objective To predict the core targets and action pathways of Hedysari Radix based on UPLC-MS/MS and network pharmacology methods,and to verify the results of network pharmacology by molecular docking and molecular dynamics techniques.This article aims to investigate immune regulation mechanism of effective components absorbed into blood from Hedysari Radix.Methods Qualitative quantification of effective components absorbed into blood from Hedysari Radix were operated by using UPLC-MS/MS technique.The corresponding targets of effective components absorbed into blood from Hedysari Radix were screened by TCMSP and HERB databases.Targets of immune-related disease were obtained through DisGeNET,OMIM,TTD,and MalaCards databases.The network of"components absorbed into blood from Hedysari Radix-immune-related diseases"was then constructed.GO and KEGG enrichment analysis and mapped the PPI network were performed.Molecular docking and molecular dynamics techniques were applied for validation.Results A total of 8 prototype components absorbed into blood,synergistically acting on 101 targets,were identified by UPLC-MS/MS.They mediated 538 biological processes including immune response,positive regulation of gene expression,receptor binding,and cytokine activity.Meanuhile,116 signaling pathways,such as HIF-1,Toll-like receptor,JAK-STAT,T cell receptor,PI3K-Akt,and FoxO etc.were involved.The core targets were MAPK14,PTGS2,MMP9,PPARG,CCND1,etc..The results of molecular docking showed that formononetin and calycosin had strong docking binding activity with MAPK14.And molecular dynamics simulations further demonstrated that the binding between MAPK14 and formononetin or calycosin had good structural stability and binding affinity.Conclusion The results of serum pharmacochemistry,network pharmacology and molecular dynamics were verified to reveal the material basis and mechanism of Hedysari Radix in regulating immunity.The aim of this study is to provide scientific basis for its immunomodulatory mechanism.

Effect of statins on occurrence of infection and infection-related mortality: a meta-analysis / 南方医科大学学报

<p><b>OBJECTIVE</b>To systematically review whether statins can reduce the risk of infection and infection-related mortality.</p><p><b>METHODS</b>We searched the Cochrane Library, MEDLINE, EMBASE, PubMed, Elsevier and CBM databases for randomized placebo-controlled trials of statins published by September 2013, and each trial enrolled at least 100 participants with follow-up for at least 4 weeks. Two reviewers independently assessed the quality of the included studies and extracted the relevant data for analysis using Stata 12.0 software.</p><p><b>RESULTS</b>Sixteen trails involving a total of 48973 patients were included in our meta-analysis. The results showed that statins significantly reduced the risk of infection (OR=0.93, 95% CI 0.89 to 0.98, P=0.004) compared to placebo but did not significantly lower infection-related mortality (OR=0.96, 95% CI 0.82 to 1.12, P=0.592).</p><p><b>CONCLUSION</b>Statins can significantly reduce the risk of infection but does not lower infection-related mortality.</p>

Correlation between serum marker variations and pulmonary hypertension secondary to chronic obstructive pulmonary disease / 南方医科大学学报

<p><b>OBJECTIVE</b>To examine the correlation of the changes in the serum markers (C-reactive protein, endothelin-1, interleukin-6, and brain natriuretic peptide) with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension secondary to COPD.</p><p><b>METHODS</b>A total of 174 COPD patients with acute exacerbation, admitted between February 2011 and February, 2013, were enrolled in this study, with 43 volunteers with normal pulmonary functions as controls. Pulmonary arterial pressure was determined by Doppler echocardiograph, and the severities (mild, moderate and severe) of PH secondary to COPD was evaluated. The levels of serum markers were determined using ELISA kits.</p><p><b>RESULTS</b>The levels of serum markers in patients with COPD was significantly elevated compared with those of the control subjects (P<0.05), and further increased in patients with pulmonary hypertension secondary to COPD (P<0.05). A positive correlation was found between these serum markers and pulmonary artery pressure in COPD patients with mild and moderate pulmonary hypertension. In patients with severe pulmonary hypertension, only the serum level of brain natriuretic peptide continued to increase with pulmonary artery pressure (P<0.05), and the other markers did not further increase.</p><p><b>CONCLUSIONS</b>Early and combined examination of these serum markers in patients with COPD can help to identify pulmonary hypertension in early stage and estimate the severity of pulmonary hypertension. Hemodynamic monitoring of the changes of these serum markers can be of important clinical value in the treatment of pulmonary hypertension secondary to COPD and in evaluation of the prognosis of COPD.</p>

A Meta-analysis of efficacy and safety of sublingual immunotherapy on allergic asthma / 中华内科杂志

Objective To evaluate the efficacy and safety of sublingual immunotherapy (SLIT) in patients with allergic asthma in order to provide reliable evidence for clinical application of SLIT.Methods To search published articles of randomized controlled trials (RCTs) in allergic asthma from CNKI,WANFANG,Pubmed and Medline databases.The methodological quality of trials was assessed by Jadadscale.The heterogeneity was examined by using Stata 11.0 software.Fixed effect model or random effect model was used to pool the data.The articles which could not be pooled were carried out by descriptive analysis.The Egger's and Begg's test were used to evaluate the publication bias.Results There were total 6 RCTs included in this text.Compared with control group,SLIT could significantly reduce asthma symptom scores (SMD =-0.89,95％ CI-1.36--0.43,P =0.000) and asthma medication scores (SMD =-4.53,95％CI-6.97--2.08,P =0.000),but not forced expiratory volume (FEV1) of lung function (SMD =0.19,95％ CI-0.02-0.41,P =0.078),neither serum sIgE levels (SMD =0.05,95％ CI -0.58-0.69,P =0.870).There were no obvious adverse events reported after treatment of SLIT.No publication bias were indicated by Egger's and Begg's tests.Conclusion SLIT significantly reduces asthma symptom scores and medication scores,suggesting that SLIT is a safe and effective approach of immunotherapy.However,it still needs more highly qualified studies of RCTs to prove.

Calcineurin/NFAT signaling pathway mediates endothelin-1-induced pulmonary artery smooth muscle cell proliferation by regulating phosphodiesterase-5 / 南方医科大学学报

<p><b>OBJECTIVE</b>To examine whether calcineurin/NFAT signaling pathway mediates endothelin-1 (ET-1)-induced proliferation of pulmonary artery smooth muscle cells (PASMCs) by regulating phosphodiesterase-5 (PDE5) and the effect of the selective calcineurin inhibitor cyclosporine A and PDE5 inhibitor sildenafil on ET-1-induced PASMC proliferation.</p><p><b>METHODS</b>PASMCs were treated with ET-1 to stimulate their proliferation with or without prior treatment of the cells with CsA or sildenafil. Calcineurin activity in the cells was measured using a calcineurin activity assay kit, PDE5 expression examined using immunoblotting, and cGMP level detected using a cGMP direct immunoassay kit. PASMC proliferation following the treatments was determined using [(3)H]thymidine incorporation assay.</p><p><b>RESULTS</b>ET-1 caused a 2.05-fold increase in the cellular calcineurin activity, a 1.80-fold increase in PDE5 expression, and a 3.20-fold increase in the DNA synthesis rate, and reduced the cGMP level by 67%. Pretreatment of the cells with Cyclosporine blocked the effects of ET-1, and PDE5 inhibition by sildenafil pretreatment also abolished ET-1-induced reduction of cGMP level in the cells. Both Cyclosporine and sildenafil suppressed ET-1-stimulated PASMC proliferation.</p><p><b>CONCLUSION</b>Activation of calcineurin/NFAT signaling pathway mediates ET-1-induced PASMC proliferation by stimulating PDE5 expression, which further degrades cGMP. Both Cyclosporine and sildenafil can suppress ET-1-stimulated PASMC proliferation in vitro.</p>