Screening and bioinformatics analysis of key autophagy-related genes in alcoholic hepatitis / 器官移植

Objective To screen key autophagy-related genes in alcoholic hepatitis (AH) and investigate potential biomarkers and therapeutic targets for AH. Methods Two AH gene chips in Gene Expression Omnibus (GEO) and autophagy-related data sets obtained from MSigDB and GeneCards databases were used, and the key genes were verified and obtained by weighted gene co-expression network analysis (WGCNA). The screened key genes were subject to gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) and immune infiltration analyses. Messenger RNA (mRNA)- microRNA (miRNA) network was constructed to analyze the expression differences of key autophagy-related genes during different stages of AH, which were further validated by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) in the liver tissues of AH patients and mice. Results Eleven autophagy-related genes were screened in AH (EEF1A2, CFTR, SOX4, TREM2, CTHRC1, HSPB8, TUBB3, PRKAA2, RNASE1, MTCL1 and HGF), all of which were up-regulated. In the liver tissues of AH patients and mice, the relative expression levels of SOX4, TREM2, HSPB8 and PRKAA2 in the AH group were higher than those in the control group. Conclusions SOX4, TREM2, HSPB8 and PRKAA2 may be potential biomarkers and therapeutic targets for AH.

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.

Effect of metformin on miRNA expression in type 2 diabetic patients and potential targets / 中华内分泌代谢杂志

Objective:To investigate the effect of metformin on the microRNA (miRNA) expression and screen potential target with network pharmacology analysis in patients with type 2 diabetes.Methods:Fifteen patients with new diagnosed type 2 diabetes admitted to our hospital were selected, who received metformin during hospitalization and after discharge. The expression of serum matrix metalloproteinase (MMP)-9, transforming growth factor (TGF)-β1, and myocardial fibrosis related miRNAs were compared before and 6 month after metformin treatment. In addition, gene ontology (GO) and KEGG pathway enrichment analysis were applied to analyze differential expression miRNAs showing statistical significance. Meanwhile, the network figure was established to reflect the target gene messenger RNA (mRNA) corresponding to differentially expressed miRNA.Results:Compared with pre-medication, the serum level of MMP-9 was significantly decreased after treatment ( P<0.05). Besides, the expression of homo sapiens microRNA (hsa-miR)29a-3p, hsa-miR133a-5p, hsa-miR21-5p, hsa-miR30c-5p, and hsa-miR1-3p in patients with type 2 diabetes were dramatically down-regulated by metformin ( P<0.05 or P<0.01). Results of GO analysis and KEGG pathway enrichment analysis showed that differentially expressed miRNAs were mainly concentrated in endoplasmic reticulum lumen, synapse, basement membrane and other cell components. The molecular functions such as Rho GTPase binding and participation in extracellular matrix structural constituent were exerted through biological processes such as collagen catabolic process, regulation of short-term neuronal synaptic plasticity, and axon extension, which were mainly enriched in advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway in diabetic complications, tumor necrosis factor (TNF) signaling pathway, and Wnt signaling pathway, etc. The outcome of miRNA-mRNA network analysis demonstrated that there were 230 target genes mRNAs corresponding to differentially expressed miRNA. Conclusion:Metformin could play its role in the treatment of type 2 diabetes by down regulating the expression of miRNA, participating in the transduction of related cellular signaling pathways, regulating chromatin, nucleic acid binding, and enzyme activities.

Screen of differentially expressed genes in liver cancer xenograft tissues after CDC25Agene silence / 中国肿瘤生物治疗杂志

@#Objective: To explore the genes that may be regulated by cell division cycle 25A (CDC25A) with gene chip technology, and to elucidate and verify that CDC25A has a regulatory effect on the expression of liver cancer related genes. Methods: CDC25A expression in human liver cancer HepG2 cells was silenced by siRNA interference technology and a nude mouse xenograft model of liver cancer was successfully constructed in our previous research. Affymetrix human gene expression profiling microarray was used to further screen differentially expressed genes (DEGs) after silencing CDC25A in liver cancer xenografts, and GO analysis and KEGG analysis were performed. Some of the DEGs were verified by qPCR. Results: The chip screened 188 DEGs in liver cancer xenograft tissues after CDC25A silence, including 78 up-regulated genes and 110 down-regulated genes. These DEGs mainly involved in cell proliferation, apoptosis, protein complex binding, extracellular space, etc., and associated with the changes in pathways such as focal adhesions and extracellular matrix (ECM) receptor interactions. qPCR showed that the expression of HIPK2 mRNA was up-regulated and the mRNA expressions of (microfibrillar-associated protein 5(MFAP5) and cyclin D1 (CCND1) were down-regulated, which were consistent with the results of microarray detection. Conclusion: Using human gene expression profiling chip, the DEGs in liver cancer xenograft tissues in nude mice after silencing CDC25Awere successfully screened, providing effective clues for exploring the effect of CDC25Aon the growth of liver cancer.

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.

Bioinformatics analysis of ulcerative colitis and its malignant complications and screening of potential therapeutic drugs / 上海交通大学学报（医学版）

Objective: To explore the pathogenic genes and potential drug therapeutic targets of ulcerative colitis and its malignant complications by a variety of bioinformatics analysis. Methods: Four expression profiling datasets (GSE13367, GSE9452 and GSE36807 as UC group, and GSE37283 as UCN group) downloaded from the Gene Expression Omnibus (GEO) database were jointly analyzed to identify the differential genes. Key genes related to ulcerative colitis and its malignant complications were obtained by subsequent immunoassay and gene correlation analysis, and a number of small molecule drugs with potential therapeutic effects were screened by LINCS L1000 database. Results: Eighty-six and 253 significant differentially expressed genes were identified respectively in the differential gene analysis of UC group and UCN group. The scoring analysis of the node genes in protein-protein interaction (PPI) network of UC group showed that the core gene of the network was CXCL8. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis indicated that CXCL8 mainly participated in the recruitment of neutrophils in IL-17 signaling pathway, and three small molecule drugs (butein, levocetirizine, pseudoephedrine) for CXCL8 were found based on the screening results of LINCS L1000 database. Conclusion: The core differentially expressed gene CXCL8 may be a new drug target for the treatment of ulcerative colitis and its malignant complications. The three screened small molecule drugs may have potential treatment effect on ulcerative colitis and its malignant complications.

Differentially Expressed Genes Related to Alzheimer ’s Disease and Their Bioinformatics Analysis / 中国药房

OBJECTIVE： To provide reference for interpretation of pathogenesis， early prevention and diagnosis， and selection of therapeutic targets of Alzheimer’s disease （AD）. METHODS： The gene chip dataset GSE28146 was downloaded from the NCBI public data platform GEO， and the AD-related differentially expressed genes （DEGs） were identified by using GEO2R online analysis tool. GO analysis and KEGG enrichment pathway analysis were performed by using DAVID 6.8 bioinformatics resource database. The protein-protein interaction （PPI） network analysis was performed by using STRING database and Cytoscape 3.2.1 software. RESULTS & CONCLUSIONS： A total of 1 478 AD-related DEGs were identified， consisting of 913 up-regulated genes and 565 down-regulated genes. GO function enrichment analysis showed that DEGs mainly distributed in cytoplasm， membrane， extracellular space， and induced AD via biological processes such as positive/negative regulation of transcription， positive regulation of NF-κB activity， regulation of Rho protein signaling transduction， protein phosphorylation； via protein binding， DNA binding， transcription factor activity （sequence specific DNA binding） and other molecular functions. KEGG pathway enrichment analysis showed that DEGs was enriched in cancer pathway， pulmonary tuberculosis， osteoclast differentiation， JAK/STAT signaling pathway， FoxO signaling pathway， EB virus infection and other signaling pathways. There are 1 205 nodes and 3 931 edges in the PPI network of DEGs coding protein. Among them， the key genes are SOCS3， NEDD4 and CBLB， which may be the potential target of AD development.

Effects of Serglycan on Drug Resistance of Ovarian Cancer and Its Mechanism Based on Bioinformatics / 中国药房

OBJECTIVE： To study the effects of serglycan （SRGN） on drug resistance of ovarian cancer and its mechanism. METHODS： Gene expression profile interactive analysis tool （GEPIA） was used to extract related data set of ovarian cancer and analyze the difference of mRNA expression of SRGN between normal ovary tissue and ovarian cancer tissue. Gene expression database （GEO） was adopted to obtain the difference of the mRNA expression of SRGN in cisplatin sensitive and cisplatin resistant cell lines （A2780）. STRING online database was used to screen proteins interacting with SRGN （confidence degree： 0.900， interactors： 10）. Adopted biological information annotation database （DAVID） to analysis Kyoto encyclopedia of genes and genomers（KEGG）metabolism pathway to predict the potential pathways of SRGN regulating drug resistance of ovarian cancer. Medical ontology information retrieval platform COREMINE was used to mine the biological processes of significant relationship of SRGN and ovarian cancer with drug resistance. RESULTS： mRNA expression of SRGN in ovarian cancer tissue was significantly higher than normal ovarian tissue （P＜0.05）. mRNA expression of SRGN in cisplatin resistant ovarian cancer was significantly higher than cisplatin sensitive ovarian cancer （P＜0.001）. 10 proteins interacting with SRGN were screened， including albumin， transforming growth factor β1， platelet factor 4， fibrinolysin and vascular endothelial growth factor A. SRGN participated in KEGG metabolism pathway of regulating drug resistance of ovarian cancer， including HIF1α pathway， cytokine-cytokine receptor pathway， coagulation and complement cascades pathway， etc. Biological processes included gene expression， cell growth， apoptosis and cell death. CONCLUSION： SRGN mediates drug resistance of ovarian cancer， which is associated with HIF1α signaling pathway and cytokine-cytokine receptor pathway.

Toxicology of Asari Radix et Rhizoma Based on Network Analysis / 中国实验方剂学杂志

Objective:To analyze the known mechanism of toxicology and predict the unknown toxicity in Asari Radix et Rhizoma sinensis by establishing the network relationship of compound, protein, gene and toxicant reaction. Method:After comparing the Asari Radix et Rhizoma candidate compounds obtained from the traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database and the toxicological information obtained from the Comparative Toxicogenomics Database(CTD) database, we screened out 13 toxic components from Asari Radix et Rhizoma. And use the Pharm Mapper Server website to find the detailed information of target proteins of the 13 components. The network structure of these 13 chemical components and their corresponding target proteins were drawn by using Cytospace software, and several target proteins with the highest degree of association were found. ClueGO+CluePedia plug-in of Cytospace software was applied in gene ontology(GO) enrichment analysis of genes and kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis, so as to determine the pathways through which toxic substances in Asari Radix et Rhizoma might be harmful to human body. Result:The toxic substances in Asari Radix et Rhizoma may induce tumor and cancer formation through p53 signaling pathway, interleukin(IL)-17 signaling pathway, nuclear factor(NF)-kappa B signaling pathway, tumor necrosis factor(TNF)-signaling pathway. Asari Radix et Rhizoma could inhibit the central nervous system by regulating apoptosis pathways and neurons, and may also cause other autoimmune diseases by IL-17, TNF-α pathway and apoptosis regulation. Conclusion:This study preliminarily explores related mechanisms of toxicity of Asari Radix et Rhizoma,this method can be used to predict toxicity and explain toxicity mechanism of traditional Chinese medicine.

Effects of ionizing radiation injury on oxidative phosphorylation signaling pathway in testicular tissues of mice / 中国药理学通报

Aim: To compare the differential expression of proteins in testicular tissues of ionized irradiated mice and normal mice, in order to explain the mechanism of ionizing irradiation on testicular tissue damage from proteomics perspective. Methods: The mouse ionizing radiation damage model was established by cobalt 60-ray irradiation. Comparative proteomics method, iTRAQ combined with LC-MS/MS detection technology were used to extract differentially expressed proteins of testis tissues from mouse irradiated group and normal group, then David6. 8, StringlO. 5 and Cytoscape 3. 6. 1 database were employed for KEGG enrichment analysis and interaction analysis on differential proteins. Results: Twenty-one biological signaling pathways (P <0. 05) were identified by KEGG enrichment analysis, with 13 differentially expressed proteins enriched in phosphoric oxide signaling pathways, and both were downgrades of expression. The pathway involved several subgroups of ATP synthase, cytochrome and NADH dehydrogenase, which were mainly involved in mitochondrial electron transfer, mitochondrial respiratory chain complex I assembly, ATP biosynthesis and so on. Conclusions: Ionizing radiation is responsible for the expression of oxidative phosphorylation signaling pathway in mouse testis tissues. The low expression of 13 differential proteins leads to the synthesis of cell ATP. It is an important mechanism of radiation damage.

Effects of ionizing irradiation on ribosome signaling pathway in spleen tissues of mice / 中国药理学通报

Aim To clarify the damage mechanisms of ionizing radiation on mouse spleen tissues and analyse differential protein expression in spleen tissues of mice exposed to ionizing radiation injury and normal mice from the perspective of comparative proteomics, in order to analyse the signaling pathways involved in differential proteins. Methods The mouse ionizing radiation injury model was established by 5 Gy 60Co-y ray, and the mouse spleen tissue was extracted in the ionizing radiation group and normal group, then ITRAQ combined with LC-MS/MS detection technology were used to screen differentially expressed proteins of spleen tissues from ionizing radiation group and normal group. Results A total of 17 biological signaling pathways were identified by KEGG pathway enrichment analysis(P <0. 0 5) , in which 37 differential expressed proteins were enriched in the ribosome signaling pathway pathway , including 36 differential expressed proteins downregulated and one differential expressed protein up-regulated. These pathway involved several multiple subunit proteins, such as ribosome proteins, 60S ribosome proteins and 40S ribosome proteins, which were mainly involved in biological processes, such as translation of proteins, structural composition of ribosome and so on. Conclusions Ionizing radiation causes 37 differential proteins involved in ribosome signaling pathway of mouse spleen tissues, including 36 differential expressed proteins down-regulated and one differential expressed protein up-regulated. The disturbance of protein synthesis in spleen tissues is an important mechanism of ionizing radiation injury.

Expression of MiR-455-5p in epithelial ovarian cancer and its target gene function / 实用肿瘤学杂志

Objective The aim of this study was to investigate the expression of miR-455-5p in epithelial ovarian cancer and its effect on the development of epithelial ovarian cancer. Methods The miRNA expression data of normal ovarian epithelial tis-sues and epithelial ovarian cancer tissues GSE83693 were downloaded from the GEO database. Differential expression analysis was used to obtain differential expression data of miRNAs in epithelial ovarian cancer. The expression of miR-455 -5p was analyzed whether there is difference expression between normal ovarian epithelium and epithelial ovary cancer tissues; qRT-PCR was used to verify the differential expression prediction results; bio-informatics software was used to analyze the KEGG pathway enrichment and GO gene function annotation of miR-455-5p target genes,and to explore the disorders of dyregulated miR-455-5p in the devel-opment of epithelial ovarian cancer. Results A total of 101 cases of differentially expressed miRNAs were screened,34 cases were up-regulated and 67 cases were down-regulated. Among them,miR-455-5p was down-regulated significantly(P<0. 01),and the different fulds were -2. 9019. The results of qRT-PCR showed that the expression of miR-455-5p in epithelial ovarian cancer cells(SKOV-3,OVCAR-3 and A2780)was significantly lower than that in normal ovarian epithelial cells(IOSE-80),and the dif-ferential expression was statistically significant(P<0. 05). The results of KEGG pathway enrichment analysis showed that miR-455-5p regulated target genes mainly involved in five pathways,including TGF-β signaling pathway,Hippo signaling pathway,ECM-receptor interaction,transcriptional dysregulation pathway in cancer,and chronic granule cellular leukemia,which were associated with tumors. GO functional annotation analysis showed that the target genes regulated by miR-455-5p in the above pathway was mainly involved in protein phosphorylation,promoted cell proliferation and migration,inhibited apoptosis,promoted epithelial-mesenchymal transition,regulated transcription and regulated cell cycle,etc. ,which associated with tumorigenesis. Conclusion The expression of miR-455-5p is down-regulated in epithelial ovarian cancer. The miR-455-5p target genes are involved in the pathogenesis and function of epithelial ovarian cancer,and are associated with the development of epithelial ovarian cancer.

A Method Based on the Complex Network for Mining the System Biological Information of Scutellaria Barbata D. Don / 世界科学技术-中医药现代化

Scutellaria barbata D. Don is widely used in TCM clinical practice, so it is important to delve the information of its system biology. In this paper, we integrate its natural compounds and genomics information. The Herb-Prince complex networks algorithm is used to delve potential associated genes, gene families and KEGG signal pathways for Scutellaria barbata D. Don, and the information is verified by literature. The top 100 genes, 4 gene families and 10 KEGG signaling pathways were found. The related results are highly consistent with the clinical and pharmacological studies of Scutellaria barbata D. Don, which provide decision support for researchers to study pharmacological activities of Scutellaria barbata D. Don at the molecular level.

Gene chip analysis of differentially expressed genes in transgenic SlNAC1 Arabidopsis / 生物工程学报

Studies have shown that some plant-specific NAC (NAM, ATAF1/2, CUC2) transcription factors may increase plants resistance to stress. We screened the genes differentially expressed in transgenic SlNAC1 Arabidopsis compared to the wild type by cDNA microarry, to provide scientific basis for studying the genes related to abiotic stress responses in transgenic Arabidopsis. There were 3 046 genes differentially expressed more than twice in the total 43 604 genes of transgenic SlNAC1 Arabidopsis. Gene ontology analysis was used on genes differentially expressed more than five-fold. Genes relevant to cellular components occupied 33.05%, genes correlated with molecular function accounted for 33.95% and genes pertinent to biological process constituted a 33.00% portion. The genes differentially expressed more than twice were processed through kyoto encyclopedia of genes and genomes pathways enrichment (KEGG) analysis. The total 2 431 genes were involved in 88 different signaling pathways. The screened genes related to abiotic stress responses provide direction and theoretical support for the following research on the downstream genes regulated by NAC and construction of the regulatory networks.

Transcriptomics of therapeutic effect of Huangqi Liuyi decoction in treating type 2 diabetes / 中国中药杂志

In this study, Illumina sequencing platform was applied in sequencing rat pancreas, counting expression of target points, analyzing expression differences among blank group, model group and Huangqi Liuyi decoction group and exploring the therapeutic effect and mechanism of Huangqi Liuyi decoction on type 2 diabetes mellitus. According to the result, 24.25% of these genes belonged to the unknown functional class, which was the largest classification unit according to the classification analysis of genes by eggNOG. The rest were classified as energy conversion, amino acid transport and metabolism, nucleotide transport and metabolism, carbohydrate transport and metabolism, coenzyme transport and metabolism, and lipid transport and metabolism, etc.Huangqi Liuyi decoction may play a therapeutic role in the treatment of type 2 diabetes mellitus through four metabolic pathways, namely environmental information processing, cellular process, organismal system and human diseases according to KEGG enrichment analysis. This study shows that, Huangqi Liuyi decoction can significantly improve the fasting blood glucose and glycosylated hemoglobin in type 2 diabetic rats.

Gene expression profiles and bioinformatics analysis of sublethal-irradiated rat hepatoma cells / 肿瘤

Objective: To identify the changes of gene expression profiles and metastasis ability of rat hepatoma cell line McA-RH7777 after sublethal irradiation, and to explore the underlying molecular mechanism. Methods: Rat hepatoma McA-RH7777 cells were received single exposure of 6 Gy X-ray. Then, the remaining McA-RH7777 cells were continuously passaged and named as McARH7777- 6Gy. The gene expression profiles of McA-RH7777 and McA-RH7777-6Gy cells were detected by gene microarray and compared. Subsequent bioinformatic analysis of the genes with significant changes in expression levels were performed by DAVID software (including GO-analysis and KEGG-analysis). The mRNA expression levels of tissue inhibitor of metalloproteinase 2 (TIMP2), SMAD family member 2 (SMAD2) and MET proto-oncogene in McA-RH7777 and McA-RH7777-6Gy cells were detected by real-time fluorescent quantitative PCR to verify the difference in gene expression profiles of the two cells. The migration and invasion abilities of McA-RH7777 and McA-RH7777-6Gy cells were detected by scratch wound healing assay and Transwell chamber assay, respectively. Results: The gene microarray showed that the expressions of a series of tumor-related genes were changed in McA-RH7777-6Gy cells as compared with wild-type McA-RH7777 cells. Real-time fluorescent quantitative PCR showed that the relative expression levels of TIMP 2, SMAD 2 and MET in McA-RH7777-6Gy cells were raised by 13.000, 14.516 and 6.384 times as compared with McA-RH7777 cells, respectively. GO analysis showed that the remarkably changed genes mainly located in tumor metastasis-associated biological processes, such as Ras protein signal transduction, cell cycle arrest, cell migration, cell adhesion, negative regulation of apoptotic process, positive regulation of cell proliferation, positive regulation of epithelial to mesenchymal transition and positive regulation of MAP kinase activity. KEGG analysis showed these genes mainly involved in proteoglycans signaling pathway, phosphoinositide-3 kinase (PI3K)-protein kinase B (PKB, Akt) signaling pathway, viral carcinogenesis pathway, FoxO signaling pathway, Rap1 signaling pathway, Hippo signaling pathway, Ras signaling pathway, etc. The scratch healing and Transwell chamber tests showed that the migration and invasion abilities of McA-RH7777-6Gy cells were significantly enhanced as compared with McA-RH7777 cells (both P < 0.001). Conclusion: After sublethal radiation, the migration and invasion abilities of hepatoma cells are significantly enhanced, which may be related to the changes of gene expressions in metastasis-associated pathways.

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.

Study of synergistic mechanism in the combination ofberberine and evodiamine from the perspective of miRNA / 中国药理学通报

Aim To explore the mechanisms of action (MOA) of synergistic anticancer function in the combination of berberine and evodiamine.Methods We first analyzed the action of suppression in the drug combination from the cell level and validated the dose scope as well as ratio of concentration in synergistic effects of drug combination.Then, the miRNA chip of liver cancer cell BEL-7402 under different treatment was analyzed.By building the miRNA-mRNA network, the MOA of the synergistic drug combination was illustrated.Results Berberine and evodiamine used in combination could significantly synergistically suppress the proliferative ability of liver cancer cells.The special differentially expressed miRNAs (DEmiRNAs) mainly participated in some cancer proliferation-related pathways and biological processes, such as MAPK signaling pathway, endocytosis pathway and insulin signaling pathway.The special target genes influenced by the drug combination not only covered three kinds of membrane receptors, but also took part in the regulation of downstream pathways.Conclusions From the regulation of miRNAs, it is clear that berberine may play a primary role in the synergistical suppression activity of the drug combination in cancer cells.The discovery of synergistic MOA in the combination of berberine and evodiamine from the miRNA level will provide a new guidance to explore more synergistic drug combinations in the future.

miR-410 expression and bioinformatics analysis of its predicted target genes in systemic lupus erythematosus / 中国免疫学杂志

Objective:To detect expression level of miR-410 in patients with systemic lupus erythematosus (SLE),and to expose the role of miR-410 and its target genes by bioinformatics methods.Methods:Expression level of miR-410 were detected by quantitative RT-PCR in peripheral blood mononuclear cells of SLE patients,and miR-410 sequence,its target genes and Genecards database were analyzed,and analysis of GO enrichment and KEGG Pathway was further performed.Results:miR-410 expression was significantly reduced in SLE patients,and its nucleotide sequence was highly conserved among species.These genes that were predicted to be regulated by miR-410 and associated with LE pathogenesis,included FASLG,CSF2,IFNAR2,MAPK1,PLCG2,IL4 and other genes.Analysis of GO enrichment revealed that miR-410's target genes were involved in cell growth,proliferation,programmed cell death,cell differentiation,immune system development and other biological activities.Analysis of KEGG Pathway showed that the target genes of miR-410 were significantly enriched in a series of signaling pathways including pathways in cancer,cytokine-cytokine receptor interaction,glioma,melanoma,TGF-β and JAK-STAT signaling pathway.Conclusion:miR-410 maybe directly regulate its target molecules,mediate various signal pathway networks,thus participate in the occurrence and development of SLE.

Study on Regulatory Mechanism and Regulation of Traditional Chinese Medicine on TRPV1 and Related Cytokines among Children Bronchial Asthma / 世界科学技术-中医药现代化

This study was aimed to explore regulatory mechanism of TRPV1 and related cytokines on children bronchial asthma and to study regulation of traditional Chinese medicine (TCM) on TRPV 1 and its related cytokines.Through KEGG database combined with literature search,the preliminary regulatory network of children bronchial asthma was drawn.And regarding the key nodes in the network,literature and database searches on related TCM were conducted.The results showed that the preliminary regulatory network was mapped out through KEGG database in combination with previous researches and literature search.Currently,studies had shown that emodin,baicalin,corydalis ambigua and dragon's blood had different degrees of downregulation effect on TRPV1.Yi-Shen Ping-Chuan Huo-Xue (YSPCHX)mixture suppresses the level of cytokine IL-2 and improves the level of cytokine IL-4 in a dose-dependent manner;astragalus mongholicus regulates the ratio of Th 1 to Th2,and Chuan-Fu-Ling (CFL) plaster elevates the level of IFN-γ.And both of them reduced the level of IL-4 in serum.It was concluded that the preliminary regulatory network of children bronchial asthma in this study provided certain basis for the regulatory mechanism of children bronchial asthma and treatment in TCM