Drug target inference by mining transcriptional data using a novel graph convolutional network framework

A fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cellular context in order to reveal potential on-target or off-target effects. Recently, the fast accumulation of gene transcriptional profiling data provides us an unprecedented opportunity to explore the protein targets of chemical compounds from the perspective of cell transcriptomics and RNA biology. Here, we propose a novel Siamese spectral-based graph convolutional network (SSGCN) model for inferring the protein targets of chemical compounds from gene transcriptional profiles. Although the gene signature of a compound perturbation only provides indirect clues of the interacting targets, and the biological networks under different experiment conditions further complicate the situation, the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles. On a benchmark set and a large time-split validation dataset, the model achieved higher target inference accuracy as compared to previous methods such as Connectivity Map. Further experimental validations of prediction results highlight the practical usefulness of SSGCN in either inferring the interacting targets of compound, or reversely, in finding novel inhibitors of a given target of interest.

Computerized optimization of high-performance liquid chromatographic method by using DryLab to test and isolate six cytochrome P450 probe substrates / 国际中医中药杂志

Objective DryLab software was used to assist high performance liquid chromatography (HPLC) method to test and isolate six Cytochrome P450 (CYP450) probe substrates.Methods Six CYP450 probe substrates were selected and the right HPLC method was developed and validated with the assistance of DryLab software.Results The new HPLC method with the assistance of DryLab software could test and isolate six probe substrates with degrees of isolation more than 2.00. The correlation coefficients (R> 0.999 8) indicated high linear correlation between the concentrations and the peak areas among six probe substrates. Recovery studies showed good results for all the probe substrat from 86.38% to 110.29%. And therelative standard deviation (RSD) ranged from 1.69% to 3.80% with its intra-day and inter-day precision ranging from 0.42% to 2.01%, and 1.36% to 2.29%, respectively.Conclusions The developed HPLC method with the assistance of DryLab could test and isolate six probe substrates with shortertime than the HPLC method alone.

The solubility, permeability and their interaction of daidzin and daidzein / 国际中医中药杂志

Objective The alm of this study was to determine the solubility and permeability of daldzin and daldzein and the interaction of these two components.Methods With the method inChinese Pharmacopoeia and in situ single-pass intestinal perfusion model we tested the solubility and permeability of daldzin, daldzein and their interaction.Results In pH 7.4 K-R buffer the solubility of daldzin was 6 times than daldzein and both the solubility of these two components were enhanced when they were determined together. In small intestine of rat, the permeability of daldzein was 3 times than daldzin. Daldzin could enhance the permeability of daldzein but the daldzein manifested an opposite trend.Conclusion When compared to daldzin, daldzein owned a lower solubility but a better permeability. When used together, both the solubility and permeability of daldzein would be enhanced. The solubility of daldzin could be enhanced slightly but its permeability would be reduced.

Specific siRNA targeting EGFR enhances ovarian cancer cell line SKOV-3 apoptosis / 肿瘤研究与临床

Objective To observe the influence of specific short hairpin siRNA targeting EGFR gene on apoptosis of human ovarian cancer Skov-3 cells in vitro. Methods A plasmid of a short hairpin siRNA targeting EGFR was constructed, and it was transfeeted into Skov-3 cell line by lipofectamine 2000. Human ovarian carcinoma cells of the line Skov-3 were cultured and divided into 3 groups: control group; non-specific group, transfected with non-specific plasmid vector; and specific group, transfected with specific small hairpin RNA expression vector. The expression of EGFR mRNA and protein were examined by RT-PCR and immunocytochemistry, Flow cytometry (FCM) was adopted to analyze quantitatively apoptotic cells in each group. Results After transfection of pshRNA-EGFR, mRNA and protein levels of EGFR gene in Skov-3 cells were obviously reduced. Flow cytometry analysis revealed that apoptosis could be induced in Skov-3 cells line transfected with pshRNA-EGFR in a time-dependent manner, no obvious apoptosis were detected in control group and non-specific group. Conclusion The plasmid expressive vector target at EGFR in our study is capable of suppressing EGFR expression of human ovarian cancer Skov-3 cells and inducing apoptosis, which provide a new way for the gene therapy of human ovarian cancer.

VEGF mobilizes endothelial progenitor cells to attenuate brain infarction in middle cerebral artery occlusion/reperfusion mice / 第三军医大学学报

Objective To observe the change of the number of endothelial progenitor cells(EPCs)in peripheral circulation after acute middle cerebral artery occlusion/reperfusion(MCAO/R)and to evaluate the therapeutic effect of VEGF through mobilizing bone marrow-derived EPCs in treatment of mouse brain infarction after acute MCAO/R.MethodsTotally 36 mice were randomized into MCAO/R+VEGF group,MCAO/R group and sham operation group.MCAO/R mice model was established according Longa's method.VEGF [3.3 ng/(g?d),for 7 d] was injected intraperitoneally to the mice of MCAO/R+VEGF group to mobilize bone marrow-derived EPCs.The other 2 group received an injection of normal saline.At days 1,4,7 during mobilization,neurological functions were evaluated and blood samples were taken from angular vein.Then the number of EPCs in peripheral circulation in MCAO/R group and MCAO/R+VEGF group was detected by flow cytometry.Mice were decapitated and brains sliced and stained with triphenyltetrazolium chloride(TTC)to calculate infarct volume using specific image analyzing system.Infarct volumes were calculated and compared among groups.ResultsThe number of EPCs in MCAO/R+VEGF group began to increase at day 1 after treatment,and peaked at day 4 and sustained to day 7,which was significantly larger than those in MCAO/R group and sham operation group at every time point(P