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Relationship between fusobacterium nucleatum,inflammatory mediators and microRNAs in colorectal carcinogenesis

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World Journal of Gastroenterology 2018年第47期24卷 5351-5365页

作者： 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 Department of biology UNESPUniv. Estadual PaulistaCampus of Sao Jose do Rio PretoSao Jose do Rio PretoSao Paulo 15054-000Brazil Department of Surgery and Orthopedics Faculty of MedicineUNESPUniv. Estadual PaulistaCampus of BotucatuBotucatuSao Paulo 18618-687Brazil Endoscopy Center of Rio Preto Sao Jose do Rio PretoSao Paulo 15015-700Brazil Molecular Oncology Research Center Barretos Cancer HospitalBarretosSao Paulo 14784-400Brazil Life and Health Sciences Research Institute University of MinhoCampus GualtarBraga 4710-057Portugal ICVS/3B’s-PT Government Associate Laboratory Campus GualtarBraga 4710-057Portugal Cancer biology and Therapeutics Group UCD Conway InstituteUniversity College DublinDublin D04 V1W8Ireland

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 *** 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 *** 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.

关键词： Colorectal cancer Colorectal adenoma fusobacterium nucleatum Inflammation Cytokines MicroRNAs

Up-regulation of tumor necrosis factor-a pathway survival genes and of the receptor TNfR2 in gastric cancer

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World Journal of Gastrointestinal Oncology 2019年第4期11卷 281-294页

作者： Ana flavia Teixeira Rossi Julia Cocenzo Contiero fernanda da Silva Manoel-Caetano fabio eduardo severino Ana Elizabete Silva Department of biology Sao Paulo State University–UNESP Department of Surgery and Orthopedics Faculty of Medicine Sao Paulo State University–UNESP

BACKGROUND Gastric carcinogenesis can be induced by chronic inflammation triggered by Helicobacter pylori(H. pylori) infection. Tumor necrosis factor(TNf)-α and its receptors(TNfR1 and TNfR2) regulate important cellular processes, such as apoptosis and cell survival, and the disruption of which can lead to cancer. This signaling pathway is also modulated by microRNAs(miRNAs), altering gene *** To evaluate the mRNA and miRNAs expression involved in the TNf-α signaling pathway in gastric cancer(GC) tissues and its *** Quantitative polymerase chain reaction(qPCR) by TaqMan? assay was used to quantify the RNA transcript levels of TNf-α signaling pathway(TNf, TNfR1,TNfR2, TRADD, TRAf2, CfLIP, NfKB1, NfKB2, CASP8, CASP3) and miRNAs that targets genes from this pathway(miR-19 a, miR-34 a, miR-103 a, miR-130 a,miR-181 c) in 30 GC fresh tissue samples. Molecular diagnosis of H. pylori was performed by nested PCR for gene HSP60. A miRNA:mRNA interaction network was construct using Cytoscape v3.1.1 from the in silico analysis performed using public *** Up-regulation of cellular survival genes as TNf, TNfR2, TRADD, TRAf2, CfLIP,and NfKB2, besides CASP8 and miR-34 a was observed in GC tissues, whereas mediators of apoptosis such as TNfR1 and CASP3 were down-regulated. When the samples were stratified by histological type, the expression of miR-103 a and miR-130 a was significantly increased in the diffuse-type of GC compared to the intestinal-type. However, no influence of H. pylori infection was observed on the expression levels of mRNA and miRNAs analyzed. Moreover, the miRNA:mRNA interaction network showed several interrelations between the miRNAs and their target genes, highlighting miR-19 a and miR-103 a, which has as predicted or validated target a large number of genes in the TNf-α pathway,including TNf, TNfR1, TNfR2, CfLIP, TRADD, CASP3 and *** Our findings show that cell survival genes mediated by TNf/TNfR2 binding

关键词： Gastric cancer Tumor necrosis factor-a signaling TNfR1 TNfR2 Cellular survival MicroRNAs

Sandy seepage faces as bioactive nitrate reactors:biogeochemistry,microbial ecology and metagenomics

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Geoscience frontiers 2023年第3期14卷 74-89页

作者： Shan Jiang Jie Jin Yongjun Wei Ying Wu Yixue Zhang Carlos Rocha Juan severino Pino Ibánhez Guosen Zhang Jing Zhang State Key Laboratory of Estuarine and Coastal Research East China Normal UniversityShanghai 200241China School of Pharmaceutical Sciences Key Laboratory of State Ministry of EducationKey Laboratory of Henan Province for Drug Quality Control and EvaluationCollaborative Innovation Center of New Drug Research and Safety EvaluationZhengzhou UniversityZhengzhou 450001HenanChina biogeochemistry Research Group School of Natural SciencesTrinity College DublinDublin 2Ireland Instituto de Investigacións Mariñas Consejo Superior de Investigaciones Científicas(IIM-CSIC)Eduardo Cabello 636208 VigoSpain School of Oceanography Shanghai Jiao Tong UniversityShanghai 200040China

Subterranean estuaries are highly dynamic in processing dissolved inorganic nitrogen(DIN).Here we investigate DIN turnover in surface sediments(0–20 cm depth)at the higher,medium and lower intertidal of a seepage face,i.e.,the outer “mouth”of the subterranean estuary,during four consecutive seasons in Sanggou Bay,*** the studied period,ammonium(NH_(4)^(+))and nitrite(NO_(2)^(-))concentrations in the sampled porewaters did not vary significantly with depth or *** contrast,peaks in porewater nitrate(NO_(3)^(-))concentration and decreases in δ^(15)N-NO_(3)^(-) and δ^(18)O-NO_(3)^(-) were observed in the 15–20 cm depth(bottom)sediment,particularly during summer and *** with NO_(3)^(-) production,the sediment total nitrogen was also markedly peaking in the bottom layer of the studied seepage *** with abundant heterotrophic microbes in the sediment,this NO_(3)^(-) accumulation was linked to a reaction chain including organic matter decomposition,ammonification and *** winter,porewater enrichment in total nitrogen occurred closer to the surface of the seepage face but triggered also active NO_(3)^(-) *** pattern reinforced the importance of pelagic organic matter supply on NO_(3)^(-) *** the shallower depths of the seepage face(fractionation(δ^(15)N-NO_(3)^(-) and δ^(18)O-NO_(3)^(-) and metagenomic results revealed denitrification as the main pathway for NO_(3)^(-) *** assimilation from benthic primary producers may also consume a fraction of NO_(3)^(-) at the sediment water *** NO_(3)^(-) production and removal significantly varied in magnitude with season(13.6 to 6.2 nmol cm^(-3)h^(-1)).Substrate supply was the key driver for nitrate cycling,as evidenced by the high NO3production rate in spring by comparison to *** highest NO_(3)^(-) turnover rates were found in summer,suggesting the comb

关键词： Benthic microbiota Nitrate Stable isotopes Subterranean estuary Denitrification

Burden of Cardiometabolic Risk factors on Cerebrovascular Events in a Southern Italian Population

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World Journal of Cardiovascular Diseases 2021年第2期11卷 145-152页

作者： Vincenzo Capuano federica Marchese Rocco Capuano Anna Grazia Iannone Norman Lamaida Ernesto Capuano Raffaella Sica Marzia Manilia eduardo Capuano Operating Unit of Cardiology and UTIC Mercato S. Severino Hospital Azienda Ospedaliera Universitaria di Salerno Salerno Italy

Background: Stroke is the second leading cause of death in the world and the third due to disability. However, there are few data available that identify the risk factors associated with it and their weight in different populations (population risk). Aim: Contribute to the knowledge of burden risk factors in stroke in a large cohort of Southern Italy. Methods: The data refer to a randomized Campania cohort of 1200 subjects (35 - 74 years) enrolled in 2008-09. Ten years later (2018-19) they were re-evaluated. We analyzed data from 32 patients who reported a cerebrovascular event (stroke or TIA) with the event-free group of subjects (804 subjects: 378 men and 426 women). We evaluated: absolute risk, Odds Ratio (OR), Additional Risk (AR), Risk Attributable to the Population (PAR) and, finally, the Population Attributable risk Fraction (FAP). Results:font-family:Verdana;"> In the comparison between the two groups (patients with events and patients without events) the risk factors with statistically significant differences were: age, Systolic Blood Pressure (SBP), BMI, cholesterol, triglycerides, glycemia and hyperinsulinemia. The ORs with the greatest impact were: blood glucose (5.1), BMI (3.3) and BPS (2.9). Linear regression analysis identified Glycemia and BMI as the only independent variables. The fAPs with the

关键词： Cerebrovascular Risk factors Southern Italy Risk Attributable to the Popula-tion

Trend in prevalence of uncontrolled total serum cholesterol for cardio-cerebro-vascular disease in a mediterranean area, 1988/89-2008/09

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World Journal of Cardiology 2013年第11期5卷 420-425页

作者： Vincenzo Capuano Norman Lamaida Ernesto Capuano Maria Immacolata Borrelli Rocco Capuano Elisabetta Notari Anna Grazia Iannone federica Marchese Matteo Sonderegger eduardo Capuano Department of Cardiovascular Diseases University Hospital of Salerno-Mercato S.Severino Hospital Local Health Authority

AIM: To examine trends of uncontrolled total serum cholesterol, treatment and control in a Mediterranean region(Campania). METHODS: We considered and compared the data collected as part of "Montecorvino Rovella Project" 1988-1989 and cross-sectional data from the two phases of the "VIP Project-Valle dell'Irno Prevenzione": 1998-1999(1stphase) and 2008-2009(2ndphase), in the 35-74-year-old-population. RESULTS: Data show a reduction of mean cholesterolemia in the last twenty years of 7.3 mg/dL for men and unchanged values for women. In the three surveys the mean values for serum cholesterol are in men: 205.2 ±47.1 mg/dL(1988/89), 200 ± 38.9 mg/dL(1998/99) and 197.9 ± 40.2 mg/dL(2008/09); in the women: 203.1 ± 42.5 mg/dL(1988/89), 198.9 ± 37.9 mg/dL(1998/99) and 203.3 ± 39.3 mg/dL(2008/09). Prevalence of uncontrolled high cholesterol ≥ 240 mg/dL for men decreased from 20.8%(1988/89) to 14.3%(1998/99) and 13.9%(2008/9), P = 0.002; for women the values decreased from 19.9%(1988/89), to 18.2%(1998/99) and 18.1%(2008/09), P = 0.007. Is statistically increased the number of patients treated and those treated to target. CONCLUSION: Encouraging increases in awareness, treatment, and control of hypercholesterolemia occurred from 1988 through 2008. Nevertheless, control of hypercholesterolemia remains poor.

关键词： Mediterranean diet Hypercholesterolemia Drug Heart disease Southern Italy