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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 | 胸苷酸合成酶和拓扑异构酶-1及Ki-67对伊立替康联合5-氟脲嘧啶治疗晚期大肠癌的预测价值显示文摘目的探讨胸苷酸合成酶(TS)、拓扑异构酶1(Topo1)和肿瘤增殖指标Ki67对伊立替康(CPT11)联合5氟脲嘧啶(5Fu)治疗晚期大肠癌患者的临床疗效和预后的预测价值。方法采用免疫组化方法检测了CPT11+5Fu一线治疗78例大肠癌患者的TS、Topo1和Ki67的表达,并与化疗疗效和患者的临床预后进行了分析。结果各检测指标的表达水平与临床疗效之间无关,但是临床预后不同。其中,TS低表达患者表现明显长的肿瘤进展时间(TTP,P<0.05)和存活期(OS,P<0.05);Ki67低表达也预示长的OS(P<0.05)。与单个指标相比较,两个指标的联合也不能预测临床疗效,但是对预后的判断作用明显提高。TS低表达、Ki67低表达以及TS和Ki67均低表达患者的中位TTP分别为9,8和17个月(P=0.02);TS低表达、Topo1低表达以及TS和Topo1均低表达患者的中位TTP分别为9,9和13个月(P=0.03);而Topo1低表达、Ki67低表达、Ki67和Topo1均低表达患者的中位TTP分别为8,9和11个月(P=0.05)。其中任何两个指标均低表达肿瘤的TTP和OS均明显长于高表达者(P<0.05)。结论TS、Topo1和Ki67不能预测大肠癌患者CPT11+5Fu的疗效,但对其临床预后有一定的预测作用。其中任何两个指标的联合,比单一指标对患者预后的预测价值明显提高。 | 徐建明 朱步东 Mangia Anita Simone Gianni Montemurro Severino Giuliani Francesco Maiello Evaristo Colucci Giuseppe Paradiso Angelo | 2005 | 中华肿瘤杂志2005，27，5： | 9 |
| 3 | 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 |
| 4 | H pylori status and angiogenesis factors in human gastric carcinoma显示文摘AIM: To investigate H pylori expression in gastric cancer patients in relation to primary tumor angiogenic markers, such as microvessel density (MVD), thymidine phospho- rylase (TP), vascular endothelial growth factor receptor-1 (VEGF-R1), p53 and circulating VEGF levels. METHODS: Angiogenic markers were analyzed immu- nohistochemically in 56 primary gastric cancers. H pylori cytotoxin (vacA) and the cytotoxin-associated gene (cagA) amplification were evaluated using PCR assay. Serum H pylori IgG antibodies and serum/plasma circulating VEGF levels were detected in 39 and 38 patients by ELI- SA, respectively. RESULTS: A total of 69% of patients were positive for circulating IgG antibodies against H pylori. cagA-positive H pylori strains were found in 41% of gastric patients. vacA was found in 50% of patients; s1 strains were more highly expressed among vacA-positive patients. The presence of the s1 strain was signifi cantly associ- ated with cagA (P = 0.0001). MVD was signifi cantly cor- related with both tumor VEGF expression (r = 0.361, P = 0.009) and serum VEGF levels (r = -0.347, P = 0.041).Conversely, neither VEGF-R1 expression nor MVD was related to p53 expression. However, H pylori was not related to any angiogenic markers except for the plasma VEGF level (P = 0.026). CONCLUSION: H pylori antigen is related to higher plasma VEGF levels, but not to angiogenic character- istics. It can be hypothesized that the toxic effects of H pylori on angiogenesis occurs in early preclinical dis- ease phase or in long-lasting aggressive infections, but only when high H pylori IgG levels are persistent. | Anita Mangia Annalisa Chiriatti Girolamo Ranieri Ines Abbate Maria Coviello Giovanni Simone Francesco Alfredo Zito Severino Montemurro Antonello Rucci Alfredo Di Leo Stefania Tommasi Pasquale Berloco Jian Ming Xu Angelo Paradiso | 2006 | World Journal of Gastroenterology2006，12，34： | 5 |
| 5 | Up-regulation of tumor necrosis factor-a pathway survival genes and of the receptor TNFR2 in gastric cancer显示文摘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 expression.AIM To evaluate the mRNA and miRNAs expression involved in the TNF-α signaling pathway in gastric cancer(GC) tissues and its relationship.METHODS 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 databases.RESULTS 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 CASP8.CONCLUSION Our findings show that cell survival genes mediated by TNF/TNFR2 binding is up-regulated in GC favoring its pro-tumoral effect, while pro-apoptotic genes as CASP3 and TNFR1 are down-regulated, indicating disbalance between apoptosis and cell proliferation processes in this neoplasm. This process can also be influenced by an intricate regulatory network of miRNA:mRNA. | Ana Flavia Teixeira Rossi Julia Cocenzo Contiero Fernanda da Silva Manoel-Caetano Fabio Eduardo Severino Ana Elizabete Silva | 2019 | World Journal of Gastrointestinal Oncology2019，11，4： | 5 |
| 6 | Synthesis of highly fluorescent carbon dots from lemon and onion juices for determination of riboflavin in multivitamin/mineral supplements显示文摘In this work, lemon and onion biomasses commonly found in street markets are for the first time used to develop a facile, fast and low-cost one-step microwave-assisted carbonization method for synthesis of highly fluorescent carbon dots (CDs). The structure and optical properties of CDs were investigated by TEM, XRD, XRF, UV-Vis, FTIR, and fluorescence spectroscopy. CDs displayed satisfactory optical pro-prieties, a high quantum yield of 23.6%, and excellent water solubility, and the particle size was 4.23-8.22 nm with an average diameter of 6.15 nm. An efficient fluorescent resonance energy transfer (FRET) between the CDs and riboflavin was achieved with CDs acting as donor and riboflavin as acceptor. A linear relationship between FRET and the riboflavin concentration from 0.10 to 3.0 μg/mL was observed, allowing the development of an accurate and fast analytical method to determine this vitamin in multivitamin/mineral supplements. Despite the potential interferences in these supplements, CDs were selective for riboflavin under optimized conditions. A paired t-test at a 95% confidence level indicated no statistically significant difference between the proposed and the reference methods. Recovery test presented values ranged from 96.0% to 101.4%. The limit of detection and relative standard deviation were estimated at 1.0 ng/mL and <2.6% (n = 3), respectively. CDs were successfully synthesized in a domestic microwave oven (1450 W, 6 min), presenting satisfactory parameters when compared with results of other studies reported in the literature, suggesting that the proposed method is a potentially useful method for the synthesis of CDs and determination of riboflavin. | Severino S. Monte-Filho Stefani I.E. Andrade Marcelo B. Lima Mario C.U. Araujo | 2019 | Journal of Pharmaceutical Analysis2019，9，3： | 4 |
| 7 | Resveratrol corrects aberrant splicing of RYR1 pre-mRNA and Ca2+ signal in myotonic dystrophy type 1 myotubes显示文摘Myotonic dystrophy type 1(DM1) is a spliceopathy related to the mis-splicing of several genes caused by sequestration of nuclear transcriptional RNA-binding factors from non-coding CUG repeats of DMPK pre-mRNAs. Dysregulation of ryanodine receptor 1(RYR1), sarcoplasmatic/endoplasmatic Ca^2+-ATPase(SERCA) and α1 S subunit of voltage-gated Ca^2+ channels(Cav1.1) is related to Ca^2+ homeostasis and excitation-contraction coupling impairment. Though no pharmacological treatment for DM1 exists, aberrant splicing correction represents one major therapeutic target for this disease. Resveratrol(RES, 3,5,4′-trihydroxy-trans-stilbene) is a promising pharmacological tools for DM1 treatment for its ability to directly bind the DNA and RNA influencing gene expression and alternative splicing. Herein, we analyzed the therapeutic effects of RES in DM1 myotubes in a pilot study including cultured myotubes from two DM1 patients and two healthy controls. Our results indicated that RES treatment corrected the aberrant splicing of RYR1, and this event appeared associated with restoring of depolarization-induced Ca^2+ release from RYR1 dependent on the electro-mechanical coupling between RYR1 and Cav1.1. Interestingly, immunoblotting studies showed that RES treatment was associated with a reduction in the levels of CUGBP Elav-like family member 1, while RYR1, Cav1.1 and SERCA1 protein levels were unchanged. Finally, RES treatment did not induce any major changes either in the amount of ribonuclear foci or sequestration of muscleblind-like splicing regulator 1. Overall, the results of this pilot study would support RES as an attractive compound for future clinical trials in DM1. Ethical approval was obtained from the Ethical Committee of IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy(rs9879/14) on May 20, 2014. | Massimo Santoro Roberto Piacentini Alessia Perna Eugenia Pisano Anna Severino Anna Modoni Claudio Grassi Gabriella Silvestri | 2020 | Neural Regeneration Research2020，15，9： | 3 |
| 8 | Incremental value of thoracic ultrasound in intensive care units:Indications,uses,and applications显示文摘Emergency physicians are required to care for unstable patients with life-threatening conditions, and thus must make decisions that are both quick and precise about unclear clinical situations. There is increasing consensus in favor of using ultrasound as a real-time bedside clinical tool for clinicians in emergency settings alongside the irreplaceable use of historical and physical examinations. B-mode sonography is an old technology that was first proposed for medical applications more than 50 years ago. Its application in the diagnosis of thoracic diseases has always been considered limited, due to the presence of air in the lung and the presence of the bones of the thoracic cage, which prevent the progression of the ultrasound beam. However, the close relationship between air and water in the lungs causes a variety of artifacts on ultrasounds. At the bedside, thoracic ultrasound is based primarily on the analysis of these artifacts, with the aim of improving accuracy and safety in the diagnosis and therapy of the various varieties of pulmonary pathologic diseases which are predominantly 'water-rich' or 'air-rich'. The indications, contraindications, advantages, disadvantages, and techniques of thoracic ultrasound and its related procedures are analyzed in the present review. | Biagio Liccardo Francesca Martone Paolo Trambaiolo Sergio Severino Gian Alfonso Cibinel Antonello D'Andrea | 2016 | World Journal of Radiology2016，8，5： | 2 |
| 9 | A convenient synthesis by microwave irradiation of an active metabolite (EXP-3174) of losartan显示文摘 | Vincenzo Santagada Ferdinando Fiorino Elisa Perissutti Beatrice Severino Sara Terracciano Cleber Evandro Teixeira Giuseppe Caliendo | 2003 | Tetrahedron Letters2003，，6： | 1 |
| 10 | Multiple interference of the human papillomavirus - 16 E7 oncoprotein with the functional role of the metastasis suppressor Nm23 - H1 protein 显示文摘 | Mileo AM Piombino E Severino A | 2006 | J Bioenerg Biomembr2006，38，34： | 1 |
| 11 | Low-dose dexamethasone in the rat:a model to study insulin rasistance显示文摘 | Brizzi P Solinss A | 2002 | Am J Physiol Endocrinol Metab2002，283，2： | 1 |
| 12 | Expression of type HI re-ceptor tyrosine kinase FLT3 and KIT and response to their ligandsby acute myeloid leukemia blasts 显示文摘 | Stacchini A Fubini L Severino A | 1996 | Leukemia1996，10，10： | 1 |
| 13 | C-type natriuretic peptide expression in patients with chronic heart failure: effects of aerobic training 显示文摘 | Passino C Del Ry S Severino S | 2008 | Eur J Cardiovasc Prev Rehabil2008，15，2： | 1 |
| 14 | The usefulness of pulsed tissue Doppler for the clinical assessment of right ventricular function显示文摘 | Galderisi M Severino S Cicala S | 2002 | Ital Heart J2002，3，： | 1 |
| 15 | The promoter of a gene encoding an isoflavone reductase-like protein in coffee ( Coffea arabica ) drives a stress-responsive expression in leaves显示文摘 | Marcos Brandalise Fabio E. Severino Mirian P. Maluf Ivan G. Maia | 2009 | Plant Cell Reports2009，，11： | 1 |
| 16 | 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 |
| 17 | Neuroradiologic findings and follow-up with magnetic resonance imaging of the genetic forms of haemophagocytic lymphohistiocytosis with CNS involvement显示文摘 | Rego I Severino M Micalizzi C | 2012 | Ped- iatr Blood Cancer2012，58，5： | 1 |
| 18 | Chemical composition and antifungal potential of Brazilian propolis against Candida spp.显示文摘 | Irlan Almeida Freires Vanessa Cristina Pin Piazentin Queiroz Vivian Fernandes Furletti Masaharu Ikegaki Severino Matias de Alencar Marta Cristina Teixeira Duarte Pedro Luiz Rosalen | 2016 | Journal de Mycologie Médicale2016，，： | 1 |
| 19 | Effects of furadan in the brown mussel Perna pernaand in mangrove oyster Crassostrea rhizophorae显示文摘 | Alves S R C Severino P C Ibboston D P | 2002 | Marine Environmental Research2002，54，35： | 1 |
| 20 | A new fixation material for open-wedge tibial osteotomy for genu varum显示文摘 | Ribeiro CH Severino NR Cury Rde P | | 0，，05： | 1 |
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