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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 | TLR2 and TLR4 polymorphisms influence m RNA and protein expression in colorectal cancer显示文摘AIM: To evaluate the effect of promoter region polymorphisms of toll-like receptor(TLR)2-196 to-174 del and TLR4-1607T/C(rs10759932) on m RNA and protein expression in tumor tissue and of TLR4+896A/G(rs4986790) on colorectal cancer(CRC) risk.METHODS: The TLR2-196 to-174 del polymorphism was investigated using allele-specific polymerase chain reaction(PCR) and the TLR4-1607T/C and TLR4+896A/G by PCR-restriction fragment length p o l y m o r p h i s m( R F L P). W e g e n o t y p e d 4 3 4 D N A samples from 194 CRC patients and 240 healthy individuals. The m RNA relative quantification(RQ) was performed in 40 tumor tissue samples by quantitative PCR Taq Man assay, using specific probes for TLR2 and TLR4 genes, and ACTB and GAPDH reference geneswere used as endogenous controls. Protein expression was analyzed by immunohistochemistry with specific primary antibodies.RESULTS: No association was found for TLR4-1607T/C and TLR4+896A/G by three statistical models(logadditive, dominant and recessive). However, based on dominant and log-additive models, the polymorphic variant TLR2-196 to-174 del was associated with increased CRC risk [dominant: odds ratio(OR) = 1.72, 95%CI: 1.03-2.89; P = 0.038 and log-additive: OR =1.59, 95%CI: 1.02-2.48; P = 0.039]. TLR2 m RNA expression was increased in tumor tissue(RQ = 2.36) when compared to adjacent normal tissue(RQ = 1; P < 0.0001), whereas the TLR4 m RNA showed a basal expression(RQ = 0.74 vs RQ = 1, P = 0.452). Immunohistochemistry analysis of TLR2 and TLR4 protein expression was concordant with the findings of m RNA expression. In addition, the TLR2-196 to-174 del variant carriers showed m RNA relative expression 2.19 times higher than wild-genotype carriers. The TLR2 protein expression was also higher for the TLR2-196 to-174 del variant carriers [117 ± 10 arbitrary unit(a.u.) vs 95 ± 4 a.u., P = 0.03]. However, for the TLR4-1607T/C polymorphism no significant difference was found for both m RNA(P = 0.56) and protein expression(P = 0.26).CONCLUSION: Our findings suggest that TLR2-196 to-174 del polymorphism increases TLR2 m RNA expression and is associated with higher CRC risk, indicating an important role in CRC genetic susceptibility. | Marcela Alcantara Proenca Juliana Garcia de Oliveira Aline Cristina Targa Cadamuro Maysa Succi Joao Gomes Netinho Eny Maria Goloni-Bertolo érika Cristina Pavarino Ana Elizabete Silva | 2015 | World Journal of Gastroenterology2015,21,25: | 9 |
| 3 | Aquatic exercise program-modulated oxidative stress markers in patients with Parkinson's disease显示文摘Parkinson's disease is a neurodegenerative disease.Oxidative stress,i.e.,the imbalance between the generation of reactive oxygen species and the antioxidant defense capacity of the body,plays an important role in the pathogenesis of this disease.Physical exercise can regulate oxidative stress.The purpose of this study was to analyze the short-and long-term effects of an aquatic exercise program on oxidative stress levels in patients with Parkinson's disease.The aquatic exercise program was carried out during 1 month with two sessions per week(1 hour/session).Blood samples were collected at four different time points:pre-intervention,immediately,48 hours,and 30 days after the first session of aquatic exercise program.Our results revealed that water-based programs modulated antioxidant enzyme activity,increased superoxide dismutase activity,reduced catalase activity,and increased the ratio of superoxide dismutase activity to catalase activity in patients with Parkinson's disease.Compared with pre-intervention and 48 hours after the first session of aquatic exercise program,superoxide dismutase activity was higher and catalase activity was lower immediately and 30 days after the first session.Our results demonstrated that aquatic exercise program could modulate oxidative stress,mainly by the effect of antioxidant enzyme activity.These results could better help understand the target of oxidative stress in Parkinson's disease.This study was approved by the Ethics Committee of Centro Universitário Metodista IPA(approval No.1.373.911)on August 9,2019 and registered with REBEC(registration number:RBR-6 NJ4 MK). | Caroline Dani Isabel Teixeira Proenca Jessica Marinho Pamela Peccin Ivy Reichert Vital da Silva Simone Nique Vera Striebel Daniela Pochmann Viviane Rostirola Elsner | 2020 | Neural Regeneration Research2020,15,11: | 4 |
| 4 | Positional cloning of the mouse obese gene and its human homologue显示文摘 | Zhang Y Proenca R Maffei M | | 0,,: | 3 |
| 5 | Positional cloning of the mouse obsese gene and its human homologue显示文摘 | Zhang Y Proenca R Maffei M | 1994 | Nature1994,372,: | 1 |
| 6 | Positional cloning of the mouse obese gene and its human homologue 显示文摘 | Proenca R Maffei M | 1994 | Nature1994,372,: | 1 |
| 7 | Positional cloning of the mouse obese gene and its human homologue显示文摘 | Proenca R Maffei M | 1994 | Nature1994,,372: | 1 |
| 8 | Positional cloning of the mouse obese gene and its human homoiogue显示文摘 | Proenca R | 1994 | Nature1994,372,6: | 1 |
| 9 | Positional cloning of the mouse obses gene and its human homologue显示文摘 | Zhang Y Proenca R Maffei M | 1994 | Nature1994,372,: | 1 |
| 10 | Positional cloning of the mouse obese gene and its human homologue显示文摘 | Yiying Zhang Richardo Proenca Margherita Maffel | 1994 | Nature1994,372,: | 1 |
| 11 | Positional cloning of the mouse obese gene and its human homologue 显示文摘 | Proenca R Maffei M | 1994 | Nature1994,372,: | 1 |
| 12 | Grape and wine polyphenolic composition of red Vitis vinifera varieties concerning vineyard altitude 显示文摘 | Mateus N Proenca S Ribeiro P | 2001 | Cienc Teenol Aliment2001,3,2: | 1 |
| 13 | Positional cloning of the mouse obese gene and its human homologue 显示文摘 | Zhang Y Proenca R Maffei M | 1994 | Nature1994,372,6505: | 1 |
| 14 | Positional cloning of the mouse obese gene and its human homologue显示文摘 | Zhang Y Proenca R Maffei M | 1994 | Nature1994,372,6505: | 1 |
| 15 | Positional cloning of the mouse obese gene and its human homologue显示文摘 | Zhang Y Proenca R Maffei M | | Nature0,372,6505: | 1 |
| 16 | Genetic algorithms in optimal multistage distribution network planning显示文摘 | Vladimiro Miranda Ranito J V Proenca L M | 2000 | IEEE Transaction on Power Systems2000,9,4: | 1 |
| 17 | Positional cloning of the mouse obese gene and its human homologue显示文摘 | Zhang Y Proenca R Maffei M | 1994 | Nature1994,372,6505: | 1 |
| 18 | Positional cloning of the mouse obese gene and its human homologue 显示文摘 | Zhang Y Proenca R Maffei M | 1994 | Nature1994,372,: | 1 |
| 19 | Positional cloning of the mouse obese gene and its human homologue显示文摘 | Zhang Y Proenca P Mallei M | 1994 | Nature1994,372,: | 1 |
| 20 | Positional cloning of the mouse obese gene and its human homologue显示文摘 | Zhang Y Proenca R Maffei M | 1994 | Nature(Lond)1994,372,: | 1 |