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.

Differential gene expression analysis in germinating and dormant teliospores of Tilletia indica using RNA seq approach

Karnal bunt of wheat is an important quarantine disease that interrupts India’s wheat trade in the international market. The whole transcriptome of germinating and dormant teliospores of Tilletia indica was performed using the RNA Seq approach to identify germination-related genes. Approximately 63 million reads were generated using the RNA sequencing by the Illumina NextSeq500 platform. The high-quality reads were deposited in NCBI SRA database (accession: PRJNA522347). The unigenes from the pooled teliospores were 16,575 having unigenes length of 28,998,753 bases. The high-quality reads of germinating teliospores mapped on to 21,505 predicted CDSs. 9,680 CDSs were common between dormant and germinating teliospores of T. indica. 11,825 CDSs were found to be in germinating teliospores while only 91 were unique in dormant spores of pathogen. The pathway analysis showed the highest number of pathways was found in germinating spores than dormant spores. The highest numbers of CDSs were found to be associated with translation (431 in number), transport and catabolism (340), signal transduction (326), and carbohydrate metabolism (283). The differential expression analysis (DESeq) of germinating and dormant teliospores showed that 686 CDS were up-regulated and 114 CDS were down-regulated in the germinating teliospores. Significant germination-related genes in the spores were validated using qPCR analysis. Ten genes viz. Ti3931, Ti6828, Ti7098, Ti7462, Ti7522, Ti 9289, Ti 8670, Ti 7959, Ti 7809,and Ti10095 were highly up-regulated in germinated teliospores which may have role in germination of spores.Further, these differentially expressed genes provide insights into the molecular events. This first study of transcriptome will be helpful to devise better management strategies to manage Karnal bunt disease.

Bioinformatics Analysis of Cardiac Aging based on GEO Database / 医学研究杂志

Objective To explore the key genes of cardiac aging by bioinformatic analysis,and conduce to prevent and treat cardio-vascular diseases in the elderly.Methods The gene expression of GSE8146 was downloaded from the Gene Expression Omnibus(GEO)database."R"software was used to screen out differentially expressed genes in the hearts of young and old mice,and DAVID online anal-ysis tool was used for Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signa-ling pathway enrichment analysis of differentially expressed genes.Hub genes were obtained by protein-protein interaction(PPI)analy-sis based on the STRING online database.Results A total of 55 differentially expressed genes were screened,including 22 up-regula-ted genes and 33down-regulated genes.The differentially expressed genes were significantly enriched in lipid metabolism,fatty acid me-tabolism and other processes,mainly involvded in peroxisome proliferators-activated receptor(PPAR)signaling pathway and Adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK)signaling pathway.The hub genes such as Fasn,Pck1,Adipoq,Cpt1a,Pdk4,Pnpla2,Slc27a1,Hmgcs2,Cidec,Ucp3 were screened out.Conclusion Cardiac aging may be related to the disorder of cellular energy metabolism,and hub genes such as Fasn,Pck1,Adipoq,Cpt1a,Pdk4,Pnpla2,Slc27a1,Hmgcs2,Ucp3,PPAR signaling path-way and AMPK signaling pathway may play an important role in the development of cardiac aging.

Key Genes and Regulatory Networks of Acute-on-chronic Liver Failure Based on Multiple Bioinformatics Analysis / 医学研究杂志

Objective To screen key genes and pathways of acute on-chronic liver failure(ACLF)by multiple bioinformatics,and to provide theoretical basis for molecular biology studies and biomarker screening of ACLF.Methods ACLF transcriptome mRNA mi-croarray data set was downloaded from Gene Expression Omnibus(GEO),and limma package in R software was used to analyze the difference expression genes.The gene ontology(GO)function enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)anal-ysis were analyzed differential genes through David database.Protein-protein interaction(PPI)network was analyzed using STRING da-tabase,the key differential genes were screened by Cytoscape software.Results A total of 329differentially expressed genes were screened,including 185 up-regulated genes and 144 down-regulated genes.GO functional enrichment analysis obtained 385 items,in-cluding immune receptor activity,cytokine receptor activity,T cell receptor binding and other biological functions(P＜0.05).KEGG pathway enrichment analysis screened 36signaling pathways,among which the immune and inflammatory pathways including Th1 and Th2 cell differentiation,Th17 cell differentiation pathway,T cell receptor signaling pathway,primary immune deficiency,NF-κB signaling pathway and TNF signaling pathway.Among these key genes,CD3G,CD3D,IL7R,LCK,IL1R2,IL18R1,IL1R1 and MAPK14 related to ACLF were further obtained,which may become potential biomarkers and therapeutic targets of ACLF.Conclusion This study demon-strates that CD3G,CD3D,IL7R,LCK,IL1R2,IL18R1,IL1R1 and MAPK14may become the core genes related to the occurrence and development of ACLF and new therapeutic targets in the future.

Programación intrauterina de enfermedad en la vida adulta: identificación de genes cardinales asociados a hipertensión arterial, obesidad y síndrome metabólico / Intrauterine Programming of Adult Disease: Identification of Cardinal Genes Associated with Hypertension, Obesity and Metabolic Syndrome

RESUMEN Introducción: La restricción del crecimiento intrauterino es una alteración del desarrollo fetal que se caracteriza por una tasa de crecimiento durante la etapa fetal que es menor al potencial genético de crecimiento para la edad gestacional. Esta condición plantea una carga importante para la salud pública, ya que aumenta la morbimortalidad de la descendencia, a corto y a largo plazo, particularmente, por asociarse al desarrollo de enfermedad cardiovascular y metabólica en la vida adulta. Objetivos: Mediante el uso de herramientas bioinformáticas nos propusimos identificar posibles genes cardinales involucrados en la restricción del crecimiento intrauterino asociados al desarrollo de obesidad, hipertensión arterial y síndrome metabólico. Material y métodos: Obtuvimos un total de 343 genes involucrados en los fenotipos de interés e identificamos 20 genes que resultaron significativamente relevantes en el análisis de la red de interacción. Particularmente, cuatro de estos genes identificados codifican para factores de crecimiento o sus receptores, VEGFA, PDGFRB, IGF1R y EGFR. Además, identificamos genes relacionados con la insulina y el control de la homeostasis cardiovascular, como son el CTNNB1, APP, MYC y MDMD2. Por otra parte, el análisis de clústeres permitió reconocer los términos de ontología genética más significativos, entre los que se destacan aquellos relacionados con procesos biológicos de proliferación y muerte celular programada, de comunicación intercelular, del metabolismo proteico, y de desarrollo del sistema cardiovascular. Conclusiones: Los genes hallados en este estudio podrían ser de utilidad como biomarcadores putativos de la presencia de alteraciones cardiovasculares y metabólicas asociadas a la restricción del crecimiento intrauterino o potenciales blancos terapéuticos de estrategias de tratamiento orientadas al genotipo del paciente.

ABSTRACT Background: Intrauterine growth restriction is an abnormal fetal development characterized by a fetal growth rate lower than the potential genetic growth for the gestational age. This condition represents a major burden for public health systems, as it increases short and long-term morbidity and mortality in the offspring, particularly because of its association with the development of cardiovascular and metabolic disease in adult life. Objectives: The aim of the present study was to identify possible cardinal genes involved in intrauterine growth restriction associated with the development of obesity, hypertension and metabolic syndrome using bioinformatics tools. Methods: A total of 343 genes involved in the phenotypes of interest were obtained and 20 genes were identified as significantly relevant in the interaction network analysis. Specifically, four of these identified genes encode for growth factors or their receptors, VEGFA, PDGFRB, IGF1R and EGFR. We also identified genes related to insulin and cardiovascular homeostasis as CTNNB1, APP, MYC and MDMD2. Cluster analysis provided the most significant gene ontology terms, including those related to the biological processes of proliferation and programmed cell death, intercellular communication, protein metabolism and development of the cardiovascular system. Conclusions: The genes found in this study could be useful as putative biomarkers for the presence of cardiovascular and metabolic disorders associated with intrauterine growth restriction, or as potential therapeutic targets for treatment strategies directed to the patient's genotype.

MCDB: A comprehensive curated mitotic catastrophe database for retrieval, protein sequence alignment, and target prediction

Mitotic catastrophe (MC) is a form of programmed cell death induced by mitotic process disorders, which is very important in tumor prevention, development, and drug resistance. Because rapidly increased data for MC is vigorously promoting the tumor-related biomedical and clinical study, it is urgent for us to develop a professional and comprehensive database to curate MC-related data. Mitotic Catastrophe Database (MCDB) consists of 1214 genes/proteins and 5014 compounds collected and organized from more than 8000 research articles. Also, MCDB defines the confidence level, classification criteria, and uniform naming rules for MC-related data, which greatly improves data reliability and retrieval convenience. Moreover, MCDB develops protein sequence alignment and target prediction functions. The former can be used to predict new potential MC-related genes and proteins, and the latter can facilitate the identification of potential target proteins of unknown MC-related compounds. In short, MCDB is such a proprietary, standard, and comprehensive database for MC-relate data that will facilitate the exploration of MC from chemists to biologists in the fields of medicinal chemistry, molecular biology, bioinformatics, oncology and so on. The MCDB is distributed on http://www.combio-lezhang.online/MCDB/index_html/.

Genomewide analysis of microsatellite markers based on sequenced database in two anuran species

Eukaryotic and prokaryotic cell genomes exhibit multiple microsatellites. In this study, we characterized microsatellites in genomes and genes of Nanorana parkeri and Xenopus laevis. This characterization was used for gene ontology (GO) analysis of coding sequences (CDS). Compared to the genome of N. parkeri, the genome of X. laevis is larger and contains more number of microsatellites, but the diversity of both species are similar. Trinucleotide repeats in the genome of N. parkeri and dinucleotide and tetranucleotide repeats in the genome of X. laevis were the most diverse. In both the species, diversity of microsatellites was highest in intergenic regions, followed by intron and exon regions, and lowest in coding regions. Microsatellites in CDS are thus subject to higher selective pressure. Many microsatellites are concentrated upstream and downstream of genes in both species, suggesting suppression of repeats in the middle of protein–CDS. Repeats are enriched in regions near gene termini purely due to the biophysical constraints of protein structure. In GO analysis, two and five unique GO terms, only found in N. parkeri and X. laevis, respectively, indicate advantageous mutations during species evolution. Biological process, cellular component and molecular function ontology reflected in the GO analysis predicted that the microsatellites located in CDS can alter protein function and may provide a molecular basis for species adaptation to new and changing environments

Bioinformatic Analysis of Related Genes and Therapeutic Drugs of Asthma / 中国实验方剂学杂志

Objective::Bioinformatic analysis was used to compare the gene expression profile between asthma patients and healthy people, and the gene characteristics of asthma were preliminarily identified and the potential mechanism and drugs were revealed. Method::The GSE74986 gene expression profile was downloaded from the gene expression omnibus (GEO) and the differentially expressed genes (DEGs) were analyzed by GEO2R. Then the gene heat map of DEGs was made by Morpheus, and their gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis were performed by DAVID 6.8. Moreover, the protein-protein interaction (PPI) network and hub genes were constructed by String 10.5. Finally, the significant modules were analyzed by MCODE in Cytoscape 3.6.1, small molecule drugs related to asthma were screened through Coremine Medical. Result::A total of 510 DEGs were screened, including 29 up-regulated genes and 481 down-regulated genes. DEGs were mainly involved in these biological processes and pathways, including chromatin silencing, transcriptional regulation of RNA polymerase Ⅱ promoter, protein transport, messenger RNA (mRNA) processing, RNA splicing, ubiquitin-mediated proteolysis, protein processing in the endoplasmic reticulum, RNA transport, and myeloid differentiation factor (MyD)-dependent Toll-like receptor signaling pathway, platelet activation, nucleotide binding oligomerization domain (NOD)-like receptor signaling pathway and so on. A total of 9 hub genes were obtained, including T-complex protein 1 subunit theta (CCT8), T-complex protein 1 subunit alpha (TCP1), 26S protease regulatory subunit S10B (PSMC6), heat shock protein 90 alpha (HSP90A)A1, cell cycle protein C (CCNC), HSP90AB1, 26S proteasome non-ATPase regulatory subunit 6 (PSMD6), ubiquitin-specific protease 14 (USP14) and eukaryotic translation initiation factor 4E (EIF4E). Two important modules were obtained. The genes in two modules mainly involved these biological process, such as splice, ubiquitin-mediated proteolysis, protein modification, RNA modification and so on. Some potential molecular drugs for the treatment of asthma, such as anisomycin and genistein, have been developed. Conclusion::DEGs and hub genes can contribute to understanding the molecular mechanism of asthma and providing potential therapeutic targets and drugs for the diagnosis and treatment of asthma.

Study on the Effects of Ligustrazine on Gene Expression of Acute Spinal Cord Injury Model Rats Based on Transcriptome Sequencing / 中国药房

OBJECTIVE：To investigate the effects of ligustrazine on ge ne expression of acute spinal cord injury （SCI）model rats. METHODS ：Male SD rats were randomly divided into sham operation group （group A ，6 rats），model group （group B ，6 rats at each time point ，12 rats in total ）and ligustrazine intervention group （group C ，6 rats at each time point ，12 rats in total ）. Acute SCI model was established by modified Allen ’s method in group B and C. After modeling ，group C was given ligustrazine 100 mg/kg intraperitoneally ，while group A and B were given constant volume of normal saline intraperitoneally ，once a day ，for consecutive 7 d or 14 d（i.e. group B 7d and B 14d，group C 7d and C 14d）. BBB scoring was conducted in each group before modeling ， 7 and 14 days after modeling. HE and Nissl staining observation were also carried out for spinal cord specimen. The differentially expressed genes （DEGs）between group A and group B ，group B and group C were analyzed by transcriptome sequencing. The enrichment of Gene Ontology （GO）and KEGG signaling pathway was analyzed by GO database and KEGG database. RESULTS ： Compared with group A ，BBB scores of group B were decreased significantly 7 d and 14 d after modeling （P＜0.05），and the number of nerve cells and Nissl body in spinal cord tissue were decreased. Compared with group B ，BBB scores of group C were increased significantly at above time points （P＜0.05），and the number of nerve cells and Nissl body in spinal cord tissue were increased. The numbers of DEGs of group A and group B 7 d， group A and group B 14d，group B 7d and group C 7d，group B 14d FAA380076） and group C 14 d were 886，1 404，70，66，respectively. The genes with opposite expression trend included Ncmap，Prx， Gabrq， Gabrg2， etc. The enrichment cell component ， molecular function ，biological process of DEGs were different 630179114@qq.com in each group ，mainly involving lyocytosis ，lysosome，plasmamembrane，homotype protein binding ，immune response ，ion channel activity ，immune response （group A and B ）；basolateral plasma membrane ，exodeoxyribonuclease activity ，response to INF-γ （group B 7 d and C 7 d）；extracellular domain ，receptor regulatory activity ，phenolic compound metabolism process （group B 14 d and C 14 d）. DEGs enriched in cytokine-cytokine receptor interaction（group A and B ）；CAMs，complement and coagulation cascades and Hedgehog signaling pathway （group B 7d and C 7d）； retrograde endocannabinoid signaling ，neuroactive ligand-receptor interaction ，PPAR signaling pathway ，GABA ergic synapse （group B 14 d and C 14 d），etc. CONCLUSIONS ：Protective effect of ligustrazine on acute SCI model rats may be associated with inflammatory response ，immune response/regulation ，neuron ion channel ，cytokine-cytokine receptor interaction ，neuroactive ligand-receptor interaction and regulation of GABA ergic synapse activity .

Study on chemical constituents of Notoginseng Radix et Rhizoma and network pharmacology of its anti-inflammatory mechanism / 中草药

Objective: To analyze the main chemical constituents of Notoginseng Radix et Rhizoma (NRR) by ultra performance liquid chromatography quadrupole-time-of-flight hybrid mass spectrometry (UPLC-Q-TOF-MS), and to study on the mechanism of NRR with multi-components, multi-targets, and multi-pathways for the treatment of inflammatory based on network pharmacology. Methods: The main chemical components in NRR were analyzed by UPLC-Q-TOF-MS. DAVID database was used to analyze gene ontology (GO) enrichment analysis and Kyoto gene and genome encyclopedia (KEGG) pathway analysis. In addition, Cytoscape 3.6.1 software was used to draw network interaction diagrams, and Image GP tool was used to draw GO bubble diagrams. Results: A total of 22 active components (ginsenoside Rh1, ginsenoside Rg1, and monolaurin) of NRR and 31 related targets (EGFR, STAT3, MAPK14) were screened. GO and KEGG pathway enrichment analysis revealed that active components of NRR acted on EGFR, STAT3, MAPK14, IL2 targets, and may regulate pathways in cancer, Cytokine-cytokine receptor Interaction, CAMs and so on. Conclusion: This study reflects the characteristics of multi-components, multi-targets, and multi-pathways of NRR in the aspect of anti-inflammatory, which may provides new ideas and methodology for further research on NRR.

Identification of prognosis-related genes in hepatocellular carcinoma based on bioinformatical analysis / 中国肿瘤生物治疗杂志

@# Objective: To identify the differentially expressed genes (DEGs) between hepatocellular carcinoma (HCC) tissues and normal liver tissues by bioinformatic methods, and to explore the intrinsic mechanism of these candidate genes involving in the occurrence and development of HCC from transcriptome level as well as the clinical significance of their associations with the prognosis of HCC patients. Methods: Gene expression profiles of GSE45267, GSE64041, GSE84402 and TCGA were downloaded from GEO (Gene Expression Omnibus) and TCGA(The Cancer GenomeAtlas), respectively. R software and Bioconductor packages were used to identify the DEGs between HCC tissues and para-cancer tissues, and then Gene Ontology (GO) Enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Protein-Protein Interaction (PPI) network analysis and survival analysis were performed. Results: Forty-six up-regulated genes and 154 down-regulated genes were screened out,and GO enrichment analysis showed that these DEGs were mainly related to cell division, proliferation, cycle regulation, oxidation-reduction process and certain metabolic pathways. KEGG pathway analysis revealed that DEGs were mainly involved in tryptophan metabolism, retinol metabolism and other metabolic pathways as well as p53 pathway. Over-expression of a panel of up-regulated genes (CCNA2, CDK1, DLGAP5, KIF20A, KPNA2 and MELK) was shown to be significantly negatively correlated with the prognosis of HCC patients in the TCGA dataset (all P<0.01). Conclusion: A set of up-regulated hub genes that are negatively correlated with prognosis will provide potential guiding value for the clinical research on the diagnosis and treatment of HCC.

Differential expression profiles of mRNA in radioresistant non-small cell lung cancer cell line A549 model using gene expression microarray / 解剖学报

Objective To investigate the radioresistance factors in non-small cell lung cancer (NSCLC)cell line A549, and provide new targets for radiotherapy sensitization drugs development. Methods Establish the stable model of radioresistant NSCLC cell line A549 under irradiation; investigate the whole-transcriptome alteration of radioresistance cell line and radiosensitive cell line using gene expression microarray; perform bioinformatic approaches gene ontology (GO) analysis and Pathway analysis. Results The expression profile microarray showed that 1410 differentially expressed genes (733 up-regulated and 677 down-regulated) were detected in resistant and sensitive strains; GO analysis showed that it was mainly related to cell cycle and DNA replication; Pathway significant enrichment analysis showed that mitogen-activated protein kiase(MAPK) signaling pathway, phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway, were mainly associated with radioresistance. Conclusion Multiple genes and signaling pathways are involved in radioresistance, further studies are needed to investigate the radioresistance factors, which could provide new targets for radiotherapy sensitization drugs development.

Biological function of intercellular adhesion molecule-1 gene in coronary heart disease and its mediated primary regulatory network: a literature based secondary analysis / 中华危重病急救医学

Objective To explore the biological function of intercellular adhesion molecule-1 (ICAM-1) gene in coronary heart disease (CHD) and to establish a primary regulatory network mediated by ICAM-1 gene. Methods The databases were searched from January 1st 2006 to December 31st 2018, including Wanfang, CNKI, VIP, Google scholar and PubMed databases for published researches on clinical study of CHD gene ICAM-1. The experimental group was CHD patients, and the control group was healthy people. Meta-analysis was employed to analyze the relationship between ICAM-1 gene and CHD. Gene Ontology (GO) and KEGG Pathway database were employed to conduct function annotation and pathway analysis. Results A total of 8 papers were enrolled into this analysis, Meta-analysis showed that the level of ICAM-1 in the experimental group was significantly higher than that in the control group [mean difference (MD) = 15.29, 95% confidence interval (95%CI) = 10.95-19.62, P < 0.000 01], surface ICAM-1 was significantly related with CHD. The GO analysis results showed that ICAM-1 molecular function mainly involved virus receptor activity, receptor activity, transmembrane signal receptor activity, protein binding, etc.; cell components mainly involve plasma membrane integral components, immune synapses, plasma membrane, etc.; biological processes mainly involve the positive regulation of cell adhesion, leukocyte adhesion, leukocyte migration and leukocyte adhesion, etc. A primary CHD regulatory network mediated by ICAM-1 gene was established based on KEGG Pathway database, and ICAM-1 was mainly expressed in endothelial cells, and further regulated the occurrence and development of CHD by promoting the proliferation of leukocytes. Conclusions ICAM-1 may regulate the occurrence and development of CHD by regulating the related biological processes of leukocytes. The successful establishment of the ICAM-1 mediated CHD regulatory network can lay a theoretical foundation for further exploring the specific regulatory role of ICAM-1 and other related genes in CHD occurrence.

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.

Proteomic Analysis on Exosomes Derived from Patients’ Sera Infected with Echinococcus granulosus

Cystic echinococcosis (CE), a zoonotic disease caused by Echinococcus granulosus at the larval stage, predominantly develops in the liver and lungs of intermediate hosts and eventually results in organ malfunction or even death. The interaction between E. granulosus and human body is incompletely understood. Exosomes are nanosized particles ubiquitously present in human body fluids. Exosomes carry biomolecules that facilitate communication between cells. To the best of our knowledge, the role of exosomes in patients with CE is not reported. Here, we isolated exosomes from the sera of patients with CE (CE-exo) and healthy donors and subjected them to liquid chromatography-tandem mass spectrometry analysis. Proteomic analysis identified 49 proteins specifically expressed in CE-exo, including 4 proteins of parasitic origin. The most valuable parasitic proteins included tubulin alpha-1C chain and histone H4. And 8 proteins were differentially regulated in CE-exo (fold change>1.5), as analyzed with bioinformatic methods such as annotation and functional enrichment analyses. These findings may improve our understanding about the interaction between E. granulosus and human body, and may contribute to the diagnosis and prevention of CE.

Analysis on Mechanism of Shema Zhichuan Liquid in Treating Asthma Based on Network Pharmacology / 中国实验方剂学杂志

Objective: To explore the potential mechanism of Shema Zhichuan liquid in treatment of asthma by network pharmacology. Method: Bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine (TCM), systematic pharmacological database and analysis platform of TCM were employed to find the components in Shema Zhichuan liquid and their targets, and asthma-related genes were obtained from the comparative toxicogenomics database (CTD). The data set of Shema Zhichuan liquid-gene and asthma-gene were imported into the Draw Venn Diagram for intersection analysis. The obtained data set of Shema Zhichuan liquid-asthma-gene was imported into String 11.0 for protein-protein interaction (PPI) analysis, and was visualized by Cytoscape 3.6.1, and further important modules were analyzed with MCODE. DAVID 6.8 was used to analyze pathway enrichment and biological process of Shema Zhichuan liquid-asthma-gene. Result: A total of 399 components and 2 099 potential targets were obtained from Shema Zhichuan liquid, 98 asthma-related targets were retrieved, 45 common genes and 16 hub genes were screened, including transforming growth factor-β1(TGF-β1), heme oxygenase-1 (HMOX1), interleukin-4 (IL-4), etc. Enrichment analysis showed that the common biological processes of Shema Zhichuan liquid and asthma were related to inflammation, contraction and remodeling of airway, cell proliferation and apoptosis, etc. The common biological pathways mainly included tumor necrosis factor (TNF) signaling pathway, receptor with high affinity for immunoglobulin E (Fc epsilon RI) signaling pathway, nuclear transcription factor-kappa B (NF-κB) signaling pathway, nucleotide binding oligomerization domain (NOD)-like receptor signaling pathway and so on. Conclusion: Shema Zhichuan liquid serves as a multi-target, multi-pathway treatment for asthma, which can provide a reference for the further research and clinical application of this preparation.

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.

Gene ontology analysis of the TNF signaling pathway in early orthodontic tooth movement of rats with periodontitis / 口腔疾病防治

Objective@#To investigate the expression and function of the TNF signaling pathway in the early stage of orthodontic tooth movement with periodontitis and to provide evidence to study the early inflammatory response in patients with periodontitis orthodontic treatment. @*Methods@#Sixteen SD rats were randomly divided into four groups: group A--12 h of orthodontic tooth movement of the bilateral maxillary first molars in rats with periodontitis; group B--periodontitis model of the bilateral maxillary first molars without orthodontic tooth movement; group C--12 h of orthodontic tooth movement of the same teeth in rats with healthy periodontium; group D--control group without operations. The bilateral maxillary first molars and surrounding periodontal tissue of each group were collected for gene chip detection. Pathway enrichment analysis, qRT-PCR and GO (gene ontology) analysis were performed to identify differential genes involved in the TNF signaling pathway. @*Results @#Gene chip results showed that the TNF signaling pathway was significantly upregulated in group A, group B and group C (P <0.01). Among the differential genes involved in the pathway, 28 were upregulated and 5 were downregulated in group A, 12 were upregulated and 4 were downregulated in group B, and 12 were upregulated and 1 was downregulated in group C (P <0.05). The most significant GO items included "response to lipopolysaccharide", "inflammatory response", "positive regulation of NF-κB transcription factor activity", "positive regulation of NF-κB import into nucleus" and "response to hypoxia"(P <0.001). qRT-PCR results showed no significant difference in TNF-α mRNA expression in group C compared with that in group D, TNF-α was upregulated in both groups A and B (P <0.01), and mRNA expression decreased in the following order: group A > group B > group C (P <0.05). Compared with group D, the expression levels of prostaglandin-endoperoxide synthase 2 (PTGS2) and interleukin-6 ( IL-6) in groups A, B and C were significantly upregulated (P <0.05), but the expression levels of PTGS2 and IL-6 in group A were lower than those in group B (P < 0.05). @*Conclusion@#The TNF signaling pathway is activated in the early stage of orthodontic tooth movement in rats with periodontitis. The pathway products participate in many biological processes and play an important role in the inflammatory response and bone absorption.

Investigation for molecular network and biological functions of Kuntai Capsule baesd on bioinformatics analysis / 中草药

Objective To investigate the potential molecular functions and the involved signaling network of Heyan®Kuntai Capsules (HYKTc) based on the ingredient-gene targets clustering by means of bioinformatics analysis. Methods The ingredients in HYKTc were obtained by the combination of previous LC-ESI-MS/MS method and searched through Traditional Chinese Medicine System Pharmacology databases. Further the gene ontology (GO) and KEGG enrichment analysis were performed with Database for Annotation, Visualization, and Integrated Discovery (DAVID) tools. Results A total of 29 chemicals were obtained in which 21 chemicals were identified by LC-ESI-MS/MS method. Afterwards, 186 gene targets were acquired in the databases. The HYKTc-gene targets clustering were highly enriched in central nervous system, breast, and ovary. Subsequent GO analysis showed that these gene targets were significantly located in the cytosol, mitochondria and extracellular matrix, mainly functioning as lipase, kinase and oxidoreductase activity. Besides, KEGG results found that these targets were involved in the PI3K-Akt, mTOR, and insulin signaling pathways. Conclusions Using TCM databases searching combined with bioinformatics methods, the potential explanations for the clinical efficiency of HYKTc were proveded for further clinical applications.

Proteomics analysis on hypolipidemic mechanisms of total phenylpropanoid glycosides from Ligustrum robustum(Roxb.)Blume in hamsters fed a high fat diet / 中国药理学与毒理学杂志

OBJECTIVE To explore the hypolipidemic mechanisms of the total phenylpropanoid glycosides from Ligustrum robustum (Roxb.)Blume (LRTPG)in hamsters using proteomics technique. METHODS The hamsters were fed with a high fat diet to induce hyperlipidemia.Then LRTPG of high (1.2 g·kg-1),medium(0.6 g·kg-1)and low(0.3 g·kg-1)doses were administrated daily for 4 weeks.Then the concentrations of plasma and hepatic lipids were determined using enzymic methods.The total protein was extracted from livers of the model group and the group treated with the high dose of LRTPG for label-free quantitative proteomics. RESULTS LRTPG significantly reduced the concentrations of plasma and hepatic lipids in hamsters fed a high fat diet. The proteomics data showed that a total of 2231 proteins were identified,and 549 proteins were found to be differentially expressed between the model group and the group treated with LRTPG.Among the 549 proteins,93 proteins were up-regulated and 59 proteins were down-regulated, and 397 proteins were absent or not. And some of these proteins were much related to the lipid metabolism. Further, gene ontology (GO) analysis indicated metabolic process, transport, oxidation-reduction process, phosphorylation, signal transduction, lipid metabolic process were the main biological processes that those differentially expressed proteins participated. KEGG pathway analysis showed that those proteins were involved in several metabolic pathways including oxidative phosphorylation,non-alcoholic fatty liver disease(NAFLD),PI3K-Akt signaling pathway, cAMP signaling pathway, cGMP-PKG signaling pathway. CONCLUSION The proteomics study could provide valuable clues to help us to understand the hypolipidemic mechanisms of LRTPG much better.