Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized trial.

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

Odorant Binding Proteins and Chemosensory Proteins in Episyrphus balteatus (Diptera: Syrphidae): Molecular Cloning, Expression Profiling, and Gene Evolution.

Aphidophagous syrphids (Diptera: Syrphidae) are important insects in agroecosystems for pollination and biological control. Insect chemoreception is essential for these processes and for insect survival and reproduction; however, molecular determinants is not well understood for these beneficial insects. Here, we used recent transcriptome data for the common hoverfly, Episyrphus balteatus, to characterize key molecular components of chemoreception: odorant-binding proteins (OBPs) and chemosensory proteins (CSPs). Six EbalCSPs and 44 EbalOBPs were cloned from this species, and sequence analysis showed that most share the characteristic hallmarks of their protein family, including a signal peptide and conserved cysteine signature. Some regular patterns and key conserved motifs of OBPs and CSPs in Diptera were identified using the online tool MEME. Motifs were also compared among the three OBP subgroups. Quantitative real-time PCR (qRT-PCR) showed that most of these chemosensory genes were expressed in chemosensory organs, suggesting these genes have chemoreceptive functions. An overall comparison of the Ka/Ks values of orthologous genes in E. balteatus and another predatory hoverfly species to analyze the evolution of these olfactory genes showed that OBPs and CSPs are under strong purifying selection. Overall, our results provide a molecular basis for further exploring the chemosensory mechanisms of E. balteatus, and consequently, may help us to understand the tritrophic interactions among plants, herbivorous insects, and natural enemies.

[Analysis of genes related to sensitivity to navalbine and docetaxel in 10 lung cancer cell lines].

OBJECTIVE: To analyze the drug-sensitivity-related genes to anti-tumor drugs navalbine (NVB) and docetaxel (Doc) in four SCLC and six NSCLC cell lines. METHODS: The sensitivity of 4 SCLC lines and 6 NSCLC lines to NVB and to Doc was determined with MTT test. The expression of 1291 anti-tumor drug sensitivity-related genes in the 10 cell lines was assayed by cDNA macroarray technique, and cluster analysis was performed to find the relationship between the results obtained by the above mentioned two measurements. RESULTS: (1) The anti-tumor effect of NVB on the 10 cell lines was apparently better than that of Doc. (2) The drug sensitivity-related genes in these 10 cell lines showed a more close positive correlation with Doc than that with NVB, whereas more genes showed negative correlation with NVB than that with Doc. But in 6 NSCLC cell lines, more genes showed the same positive or negative correlation with the two drugs. (3) 51 genes in the 10 cell lines showed correlation with Doc or NVB. 13 of them had negative correlation with Doc, 11 of them showed positive correlation. 24 of them showed negative correlation with NVB, 3 of them showed positive correlation. 67 genes in 6 NSCLC cell lines showed a correlation with sensitivity to Doc or NVB, among them 34 had negative correlation with Doc, 4 had positive correlation. 25 genes had negative correlation with NVB, 4 had positive correlation. (4) Rab 1, Rab 3, Rho B, Rho C, Rac 1, Rac 2, Gho GDI beta, CD44, integrin alpha5, integrin alpha6, integrin beta5, vinculin showed to be cytoskeleton-related genes differently expressing in SCLC or NSCLC cell lines. CONCLUSION: There is obvious difference in the drug sensitivity-related genes to NVB or Doc between SCLC and NSCLC cell lines.