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| 1 | Relationship between Fusobacterium nucleatum,inflammatory mediators and microRNAs in colorectal carcinogenesis显示文摘AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cytokine gene mRNA(TLR2, TLR4, NFKB1, TNF, IL1 B, IL6 and IL8), and potentially interacting miRNAs(miR-21-3p, miR-22-3p, mi R-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction(qPCR) TaqMan? assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma(CRA) and 43 colorectal cancer(CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability(MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.RESULTS Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA(51.8%) and more markedly in CRC(72.1%). We observed significantly greater expression of TLR4, IL1 B, IL8, and miR-135 b in CRA lesions and TLR2, IL1 B, IL6, IL8, mi R-34 a and miR-135 b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1 B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135 b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34 a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high CRC.CONCLUSION Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible mi RNA-mediated activation of TLR2/TLR4. | Marcela Alcantara Proenca Joice Matos Biselli Maysa Succi Fábio Eduardo Severino Gustavo Noriz Berardinelli Alaor Caetano Rui Manuel Reis David J Hughes Ana Elizabete Silva | 2018 | World Journal of Gastroenterology2018，24，47： | 15 |
| 2 | Upregulation of the APE1 and H2AX genes and miRNAs involved in DNA damage response and repair in gastric cancer显示文摘Gastric cancer remains one of the leading causes of cancer-related death worldwide,and most of the cases are associated with Helicobacter pylori infection.This bacterium promotes the production of reactive oxygen species(ROS),which cause DNA damage in gastric epithelial cells.In this study,we evaluated the expression of important genes involved in the recognition of DNA damage(ATM,ATR,and H2AX)and ROS-induced damage repair(APE1)and the expression of some miRNAs(miR-15a,miR-21,miR-24,miR-421 and miR-605)that target genes involved in the DNA damage response(DDR)in 31 fresh tissues of gastric cancer.Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.Analysis performed by real-time quantitative PCR exhibited significantly increased levels of the APE1(RQ=2.55,p<0.0001)and H2AX(RQ=2.88,p=0.0002)genes beyond the miR-421 and miR-605 in the gastric cancer samples.In addition,significantly elevated levels of miR-21,miR-24 and miR-421 were observed in diffuse-type gastric cancer.Correlation analysis reinforced some of the gene:gene(ATM/ATR/H2AX)and miRNA:mRNA relationships obtained also with the interaction network.Thus,our findings show that tumor cells from gastric cancer presents deregulation of genes and miRNAs that participate in the recognition and repair of DNA damage,which could confer an advantage to cell survival and proliferation in the tumor microenvironment. | Fernanda S.Manoel-Caetano Ana Flávia T.Rossi Gabriela Calvet de Morais Fábio Eduardo Severino Ana Elizabete Silva | 2019 | Genes & Diseases2019，6，2： | 5 |
| 3 | Engraftment in nonobese diabetic severe combined immunodeficient mice of human CD34^+ cord blood cells after ex vivo expansion: evidence for the amplification and self-renewal of repopulating stem cells 显示文摘 | Piacibello W Sanavio F Severino A | 1999 | Blood1999，93，11： | 1 |
| 4 | Engraftment in nonobese diabetic severe combined immunodeficient mice of human CD34^* cord blood cells after ex vivo expansion: evidence for the amplification and self-renewal of repopulating stem cells 显示文摘 | Piaeibello W Sanavio F Severino A | 1999 | Blood1999，93，： | 1 |
| 5 | Effectiveness of diode laseras adjunctive therapy to scaling root planning in the treatmentof chronic periodontitis: a meta-analysis显示文摘 | Sgolastra F Severino M Gatto R | 2013 | Lasers Med Sci2013，28，5： | 1 |
| 6 | Effectiveness of peri- odontal treatment to improve metabolic control in patients with chronic periodontitis and type 2 diabetes : a meta-analysis of random- ized clinical trials 显示文摘 | Sgolastra F Severino M Pietropaoli D | 2013 | J Periodontol2013，84，7： | 1 |
| 7 | Identification of suitable internal control genes for expression studies in Coffea arabica under different experimental conditions显示文摘 | Barsalobres-Cavallari C F Severino F E Maluf M P | | 0，，： | 1 |
| 8 | Vanadium haloperoxidases from brown algae of the Laminariaceae family显示文摘 | Almeida M Filipe S Humanes M Maia M F Melo R Severino N Da Silva J A L Da Silva J J R F Wever R | 2001 | Phytochemistry2001，57，： | 1 |
| 9 | Nd:YAG laser as an ad- junctive treatment to nonsurgical periodontal therapy: a meta- analysis显示文摘 | Sgolastra F Severino M Petrucci A | 2014 | Lasers Med Sci2014，29，3： | 1 |
| 10 | HDS Activity of Carbon-Supported Ni-Mo Catalysts Derived from Thiomo- lybdate Complexes显示文摘 | Brito J J Severino F Ninoska Delgado N | 1998 | Applied Catalysis A: General1998，173，： | 1 |
| 11 | Engraftment in nonobese severe combined immunodeficient mice of human CD34 cord blood cells after ex vivo expansion:evldence for the amplification and self-renewal of repopulating stem cells显示文摘 | Piacibello M Sanavio F Severino A | 1999 | Blood1999，93，11： | 1 |
| 12 | The selective cata- lytic reduction of no over copper-containing hematite 显示文摘 | Severino F Brito J L Agudo A L | 1998 | Catal1998，177，1： | 1 |
| 13 | Nature of copper active sites in the carbon monoxide oxidation on CuA1204 and CuCr204 spinel type catalysts显示文摘 | SEVERINO F BRITO J L LAINE J FIERRO J L G LOPEZ AGUDO A | 1998 | J Catal1998，177，1： | 1 |
| 14 | The intestinal permeation of didanosine from granules containing microspheres using the everted gut sac model显示文摘 | C F da Silva P Severino F Martins | | 0，，： | 1 |
| 15 | Microtwin reduction in 3c-sic heteroepitaxy显示文摘 | Severino A Via F L | 2010 | Appl Phys Lett2010，97，18： | 1 |
| 16 | Didanosine-loaded chitosan microspheres:optimization of fabrication process显示文摘 | C F da Silva P Severino F Martins | | 0，，： | 1 |
| 17 | Engraftment in nonobese diabetic/severe combined immonodeficient mice of human CD34 + cord blood cells after ex vivo expansion: evidence for the amplifilation and self-renewal of repopulating stem cells 显示文摘 | PiacibeUo W Sanavio F Severino A | 1999 | Blood1999，93，： | 1 |
| 18 | Chemisorption of Cu^II and CO^II chlorides and Ⅱ-diketonates on silica gel functionalized with 3-aminopropyltrimethoxysilane 显示文摘 | JOSE G P SEVERINO F O WOLFANGO E S | 2000 | Colloids and Surfaces A2000，166，13： | 1 |
| 19 | Lasers for the treat- ment of dentin hypersensitivity: a meta-analysis显示文摘 | Sgolastra F Petrucci A Severino | 2013 | J Dent Res2013，92，6： | 1 |
| 20 | Identi fication of suitable internal control genes for expression studies in Coffea arabica under different experimental conditions显示文摘 | Barsalobres-Cavallari C F Severino F E Maluf M P | 2009 | BMC Mol Biol2009，6，10： | 1 |
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