Mechanism of Shouhui Tongbian Capsules in treating constipation based on network pharmacology and molecular docking / 中国中药杂志

To explore the mechanism of Shouhui Tongbian Capsules in treating constipation by means of network pharmacology and molecular docking approach. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Bioinfoematics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN) were applied to obtain chemical components and potential targets of eight herbs in Shouhui Tongbian Capsules according to the screening principles of oral availability(OB)≥30% and drug-like property(DL)≥0.18. Disease targets relating to constipation were screened out through GeneCards, PharmGkb and other databases, drug targets were integrated with disease targets, and intersection targets were exactly the potential action targets of Shouhui Tongbian Capsules for treating constipation; PPI network of potential targets was constructed using STRING platform, and GO(gene ontology) analysis and KEGG(Kyoto encyclopedia of genes and genomes) pathway data were obtained to conduct enrichment analysis and predict its mechanism of action. Cytoscape 3.6.1 was used to construct a network of "medicinal materials-chemical components-drug targets", and the network topology analysis was carried out on the PPI network to obtain its main components and key targets. Molecular docking between components and key targets of Shouhui Tongbian Capsules verified the accuracy of network pharmacological analysis results. The PPI network analysis showed 92 chemical components, including quercetin, stigmaste-rol, aloe-emodin, rhein, and key targets for instance AKT1, MAPK1, IL6, JUN, TNF and TP53. The enrichment analysis of KEGG screened out 157 signal pathways(P<0.01), mainly involving interleukin 17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, thyroid hormone signaling pathway. Quercetin, resveratrol and lysine with top degree value had a rational conformation in docking site of protein crystal complexes. This study preliminarily showed that various active ingredients in Shouhui Tongbian Capsules could regulate multiple signaling pathways, increase intestinal smoothness and peristalsis function, ensure smooth intestinal lumen, and play a role in treating constipation by acting on key targets, such as AKT1, MAPK1, IL6 and JUN.

Study on therapeutic mechanism of Rehmanniae Radix Praeparata- Corni Fructus in sequelae of ischemic stroke based on network pharmacology technology / 中国中药杂志

In ischemic stroke sequela phase, Rehmanniae Radix Praeparata-Corni Fructus drug pair has the effect in protecting damaged neurons, but its mechanism has not been clear. In this study, network pharmacology was used to predict the mechanism of Rehmanniae Radix Praeparata-Corni Fructus in the treatment of ischemic stroke sequela. Through database search and literature retrie-val, 40 active ingredients of Rehmanniae Radix Praeparata and Corni Fructus were obtained, and their targets were obtained through STITCH and TCMSP databases. The targets of ischemic stroke sequela were obtained through OMIM,GAD,TTD and DrugBank databases. By screening the intersections of active ingredients targets and stroke treatment targets, 21 potential targets were obtained. The DAVID database was used for GO enrichment analysis and KEGG pathway analysis of potential targets. GO enrichment analysis showed that Rehmanniae Radix Praeparata-Corni Fructus were mainly involved in regulation of blood pressure, negative regulation of extrinsic apoptotic signaling and positive regulation of angiogenesis. KEGG pathway analysis showed that Rehmanniae Radix Praeparata-Corni Fructus could inhibit inflammatory response and apoptosis signaling pathway by regulating HIF-VEGFA signaling pathway in neural stem cell proliferation, TNF signaling pathway and NF-kappaB signaling pathway. Molecular docking technique was used to verify that Rehmanniae Radix Praeparata-Corni Fructus component has a good binding activity with potential targets. The results showed that in ischemic stroke sequela phase, Rehmanniae Radix Praeparata-Corni Fructus drug pair could play an important role in recovering neural function, promoting the proliferation of neural stem cells, angiogenesis, preventing neural cells apoptosis and regulating inflammatory factors.

Serum microRNA test in one Chinese early-onset familial Alzheimer's disease and preliminary analysis / 中华行为医学与脑科学杂志

Objective To determine the expression profile of serum microRNAs(miRNAs) in early-onset familial Alzheimer's disease (EO-FAD) patients. methods miRNA microarrays were performed to detect the expression profile of serum miRNAs in 2 cases of EO-FAD patients,2 cases of EO-FAD carriers and 2 cases of normal controls.Preliminary bioinformatic analysis was conducted. Result sIt was found that 21 miRNAs were up-regulated and 22 miRNAs were down-regulated in serum of EO-FAD patients,the differences were statistically significant(P<0.05).miR-5704(P=0.0002),miR-4639-3p(P=0.0195),miR-107(P=0.0204) were markedly up-regulated,miR-5572(P=0.0008),miR-204-3p(P=0.0014),miR-542-5p(P=0.0106) and miR-155-5p(P=0.0240) were markedly down-regulated.Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that the dysregulated miRNAs may be involved in the mechanism of EO-FAD by affecting neurotrophin signaling pathway.Conclusion miR-5704,miR-4639-3p,miR-107,miR-5572,miR-204-3p,miR-542-5p and miR-155-5p may be used as potential biomarkers of EO-FAD,and involved in the mechanism of EO-FAD by affecting neurotrophin signaling pathway.

Prediction of miR-199a-3p targets gene and its bioinformatics analysis / 西安交通大学学报(医学版)

Objective To provide theoretical guidance for further research on the role of miR-1 99a-3p in formation and development of bladder cancer.Methods Mature sequence of miR-1 99a-3p was analyzed;target genes and transcription factors of miRNA-1 99a-3p were predicted,and the target genes were analyzed for gene ontology (GO)enrichment and Kyoto Encyclopedia of Genes and Genome (KEGG)pathway.Then TF-miRNA-mRNA network diagram was constructed.Results Sequences of miR-1 99a-3p were highly conserved in various species.In GO analysis,the target genes of miR-1 99a-3p were enriched in many biological processes,such as regulation of cellular process,regulation of macromolecule metabolic process,and regulation of biological process (P <0.01 ).In KEGG pathway,the target genes were mainly located in bacterial invasion pathway of epithelial cells,ECM-receptor interaction pathway,PI3K-Akt signaling pathway,MAPK signaling pathway,small cell lung cancer pathway,and proteoglycans pathway in the cancer (P <0.05).According to the TF-miRNA-mRNA network diagram,the important genes that might be regulated by miR-1 99a-3p were MYC,SP1,mTOR,NFκB,and NFκB1.Conclusion miR-1 99a-3p may directly target mTOR and participate in the formation and development of bladder cancer through regulating PI3K-Akt-mTOR signaling pathway.

Microarray analysis of differentially expressed genes regulating lipid metabolism during melanoma progression.

A new hallmark of cancer involves acquisition of a lipogenic phenotype which promotes tumorigenesis. Little is known about lipid metabolism in melanomas. Therefore, we used BRB (Biometrics Research Branch) class comparison tool with multivariate analysis to identify differentially expressed genes in human cutaneous melanomas, compared with benign nevi and normal skin derived from the microarray dataset (GDS1375). The methods were validated by identifying known melanoma biomarkers (CITED1, FGFR2, PTPRF, LICAM, SPP1 and PHACTR1) in our results. Eighteen genes regulating metabolism of fatty acids, lipid second messengers and gangliosides were 2-9 fold upregulated in melanomas of GDS-1375. Out of the 18 genes, 13 were confirmed by KEGG pathway analysis and 10 were also significantly upregulated in human melanoma cell lines of NCI-60 Cell Miner database. Results showed that melanomas upregulated PPARGC1A transcription factor and its target genes regulating synthesis of fatty acids (SCD) and complex lipids (FABP3 and ACSL3). Melanoma also upregulated genes which prevented lipotoxicity (CPT2 and ACOT7) and regulated lipid second messengers, such as phosphatidic acid (AGPAT-4, PLD3) and inositol triphosphate (ITPKB, ITPR3). Genes for synthesis of pro-tumorigenic GM3 and GD3 gangliosides (UGCG, HEXA, ST3GAL5 and ST8SIA1) were also upregulated in melanoma. Overall, the microarray analysis of GDS-1375 dataset indicated that melanomas can become lipogenic by upregulating genes, leading to increase in fatty acid metabolism, metabolism of specific lipid second messengers, and ganglioside synthesis.

Differential analysis of miRNA let-7f-1-3p in Burkitt lymphoma / 白血病·淋巴瘤

Objective To explore the differential expression of microRNAs (miRNAs) in Burkitt lymphoma (BL) and their potential use as biomarkers for BL diagnosis.Methods The different miRNAs in BL from reactive hyperplasia of lymph node cases were screened by miRNA chip.The potential targets of miRNAs were predicted using miRWALK.MAS3 program was used to determine the putative functions of potential miRNA target genes by annotation using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.Results A total of 46 miRNAs (36 upregulated and 21 downregulated) were dysregulated in BL compared with reactive hyperplasia of lymph node.Interestingly,members of the let-7 family (let-7f-1-3p) was downregulated in BL.The target genes of let-7f-1-3p were predicted,and the GO enrichment analysis revealed their functions were mainly related with multicellular organismal development and regulation of transcription from RNA polymerase Ⅱ promote.KEGG pathway analysis was also carried out among the predicted target genes,which showed that they were mainly involved in TGF-beta signaling pathway and related with chronic myeloid leukemia.Conclusions The set of differentially expressed miRNAs identified here expands the range of potential diagnostic markers for BL.