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| 1 | Aging related methylation influences the gene expression of key control genes in colorectal cancer and adenoma显示文摘AIM To analyze colorectal carcinogenesis and age-related DNA methylation alterations of gene sequences associated with epigenetic clock CpG sites. METHODS In silico DNA methylation analysis of 353 epigenetic clock Cp G sites published by Steve Horvath was performed using methylation array data for a set of 123 colonic tissue samples [64 colorectal cancer(CRC), 42 adenoma, 17 normal; GEO accession number: GSE48684]. Among the differentially methylated agerelated genes, secreted frizzled related protein 1(SFRP1) promoter methylation was further investigated in colonic tissue from 8 healthy adults, 19 normal children, 20 adenoma and 8 CRC patients using bisulfite-specific PCR followed by methylation-specific high resolution melting(MS-HRM) analysis. m RNA expression of age-related 'epigenetic clock' genes was studied using Affymetrix HGU133 Plus2.0 whole transcriptome data of 153 colonic biopsy samples(49 healthy adult, 49 adenoma, 49 CRC, 6 healthy children)(GEO accession numbers: GSE37364, GSE10714, GSE4183, GSE37267). Whole promoter methylation analysis of genes showing inverse DNA methylationgene expression data was performed on 30 colonic samples using methyl capture sequencing.RESULTS Fifty-seven age-related Cp G sites including hypermethylated PPP1R16 B, SFRP1, SYNE1 and hypomethylated MGP, PIPOX were differentially methylated between CRC and normal tissues(P < 0.05, ?β≥ 10%). In the adenoma vs normal comparison, 70 CpG sites differed significantly, including hypermethylated DKK3, SDC2, SFRP1, SYNE1 and hypomethylated CEMIP, SPATA18(P < 0.05, ?β≥ 10%). In MS-HRM analysis, the SFRP1 promoter region was significantly hypermethylated in CRC(55.0% ± 8.4 %) and adenoma tissue samples(49.9% ± 18.1%) compared to normal adult(5.2% ± 2.7%) and young(2.2% ± 0.7%) colonic tissue(P < 0.0001). DNA methylation of SFRP1 promoter was slightly, but significantly increased in healthy adults compared to normal young samples(P < 0.02). This correlated with significantly increased SFRP1 m RNA levels in children compared to normal adult samples(P < 0.05). In CRC tissue the mR NA expression of 117 agerelated genes were changed, while in adenoma samples 102 genes showed differential expression compared with normal colonic tissue(P < 0.05, logF C > 0.5). The change of expression for several genes including SYNE1, CLEC3 B, LTBP3 and SFRP1, followed the same pattern in aging and carcinogenesis, though not for all genes(e.g., MGP). CONCLUSION Several age-related DNA methylation alterations can be observed during CRC development and progression affecting the m RNA expression of certain CRC- and adenoma-related key control genes. | Orsolya Galamb Alexandra Kalmár Barbara Kinga Barták árpád V Patai Katalin Leiszter Bálint Péterfia Barnabás Wichmann Gábor Valcz Gábor Veres Zsolt Tulassay Béla Molnár | 2016 | World Journal of Gastroenterology2016，22，47： | 7 |
| 2 | Thiopurine-methyltransferase variants in inflammatory bowel disease:Prevalence and toxicity in Brazilian patients显示文摘AIM:To analyze the prevalence of thiopurine-methyltransferase(TPMT)genotypes and their associationwith drug toxicity in inflammatory bowel disease(IBD)patients from southeastern Brazil.METHODS:A total of 219 consecutive patients with IBD,of which 146 had Crohn’s disease and 73 had ulcerative colitis,regularly seen at the outpatient unit of the Division of Gastroenterology at the University Hospital Pedro Ernesto of the State University of Rio de Janeiro,a tertiary referral center,were enrolled in this study from February 2009 to January 2011.We analyzed the presence of major TPMT genetic variants(TPMT*2,*3A,*3C)in IBD patients by means of a specific allele and RFLP-PCR.Genomic DNA was isolated from peripheral blood leukocytes by proteinase-K/Sodium Dodecyl Sulfate digestion and phenol-chloroform extraction.TPMT*2(C238G),TPMT*3A(G460A/A719G),and TPMT*3C(A719G)genotypes were detected by real-time polymerase chain reaction followed by direct sequencing with specific primers.Clinical data were systematically recorded,and correlated with the genotype results.RESULTS:The distribution of the selected TPMT gene polymorphism TPMT*2(C238G),TPMT*3A(G460A/A719G),and TPMT*3C(A719G)genotypes was 3.6%,5.4%,and 7.7%of the patients,respectively.Among the side effects recorded from patients taking azathioprine,14 patients presented with pancreatitis and/or an elevation of pancreatic enzymes,while 6 patients had liver toxicity,and 2 patients exhibited myelosuppression/neutropenia.TPMT polymorphisms were detected in 37/219 patients(8 heterozygous for*2,11 heterozygous for*3A,and 18 heterozygous for*3C).No homozygotic polymorphisms were found.Despite the prevalence of the TPMT*3C genotype,no differences among the genotype frequencies were significant.Although no association was detected regarding myelotoxicity or hepatotoxicity,a trend towards the elevation of pancreatic enzymes was observed for TPMT*2 and TPMT*3C genotypes.CONCLUSION:The prevalence of TPMT genotypes was high among Brazilian patients.Variants genes*2and*3C may be associated with azathioprine pancreatic toxicity in a IBD southeastern Brazilian population. | Ana Teresa P Carvalho Barbara C Esberard Renata S B Fróes Davy C M Rapozo Ana B Grinman Tatiana A Simo Juliana C V C Santos Antonio José V Carneiro Luis Felipe Ribeiro-Pinto Heitor S P de Souza | 2014 | World Journal of Gastroenterology2014，20，12： | 3 |
| 3 | Health Promotion in Adolescents: A Review of Pender's Health Promotion Model显示文摘 | Brenda J S Barbara V F | 2006 | Nurs Sci Q2006，19，4： | 1 |
| 4 | Inhibin resistance is associated with aggressive tumorigenicity of ovarian cancer cells显示文摘 | MICHAEL D S TANYA J S BARBARA C V | 2005 | Molecular Cancer Research2005，3，1： | 1 |
| 5 | Serologic response and reactogenicity to booster immunization of healthy seropositive adults with live or inactivated varicella vaccine 显示文摘 | Steven J S Barbara V S Frederick G H | 1992 | Anti Res1992，17，： | 1 |
| 6 | Totally implantable middle ear device for rehabilitation of sensorineural heating loss:Preliminary experience with the Esteem,Envoy显示文摘 | Barbara M Manni V Monini S | 2009 | Acta OtolaryngoL2009，129，： | 1 |
| 7 | Crystal structure of the outer membrane actire transporter FepA from Escherichia coif显示文摘 | Susan B Barbara S Lalitha V | 1999 | Nature structural biology1999，6，： | 1 |
| 8 | Adenosine kinase of Arabidopsis.Kinetic properties and gene expression显示文摘 | Barbara A M Li W Mike S A Yvonne Y S,Wensheng Q,Jamie S,Klaus V S | | 0，，： | 1 |
| 9 | Calcium Plus Vitamin D Supplementation and the Risk of Incident Diabetes in the Women’s Health Initiative显示文摘 | Connelly Stephanie Curb J David Howard Barbara V Kestenbaum Bryan Larson Joseph C Manson JoAnn E Margolis Karen L Siscovick David S Weiss Noel S | 2008 | Diabetes Care2008，，4： | 1 |
| 10 | Plasma adiponeclin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentr- ation precedes a decrease in whole body insulin sensitivity inhumans显示文摘 | Norberl S Barbara V Tohru F el al | 2002 | Diabetes2002，51，： | 1 |
| 11 | Synthesis of biological active tetrahydrofurofuranliganan-(syringin, pinoresinol)-mono-and bis- glucosides 显示文摘 | Barbara V Otto S Hildebert W | 1991 | Phytochemistry1991，30，9： | 1 |
| 12 | Trimetazidine improves left ventricular function and quality of life in elderly patients with coronary artery disease显示文摘 | Cristina V Mauricio W Barbara S | 2004 | Eur Heart J2004，25，： | 1 |
| 13 | Critical thinking and clinical competence:a study of their relationship in BSN seniors显示文摘 | Barbara M Edell V Butell S | 1999 | J Nuts Edu1999，38，3： | 1 |
| 14 | Brain plasticity in developmental dyslexia after phonological treatment: A beta EEG band study显示文摘 | Barbara P Chiara S Claudio V | 2010 | BehavBrainRes2010，，209： | 1 |
| 15 | Anti-solvent and co-solvent effect of CO2 on the solubility of griseofulvin in acetone and ethanol solutions显示文摘 | Barbara D G Arlette V G Pascale S | 2004 | J Supercrit Fluids2004，29，3： | 1 |
| 16 | Estimates of con- traceptive failure from 2002 national survey of family growth 显示文摘 | Kathryn K Susheela S Barbara V | 2008 | Contraception2008，77，1： | 1 |
| 17 | BMP8B Increases Brown Adipose Tissue Thermogenesis through Both Central and Peripheral Actions显示文摘 | Andrew J. Whittle Stefania Carobbio Luís Martins Marc Slawik Elayne Hondares María Jesús Vázquez Donald Morgan Robert I. Csikasz Rosalía Gallego Sergio Rodriguez-Cuenca Martin Dale Samuel Virtue Francesc Villarroya Barbara Cannon Kamal Rahmouni Miguel Lóp | 2012 | Cell2012，，4： | 1 |
| 18 | CODE-EHR:临床研究中运用结构化电子医疗记录的最佳实践框架显示文摘改善患者生存质量是全球临床医学的发展目标,大数据是实现其发展的关键所在。技术进步使结构化电子医疗记录得以常规化,也可能会改善缺失重要临床证据的问题。虽然大数据及其相关分析在新冠大流行期间发挥了重要作用,但也存在严重的缺陷。证实、核验、数据隐私以及对科学研究社会责任的践行是一项重要挑战。欧洲心脏病协会和BigData@Heart联盟已经收集了包括患者代表、临床医生、科研人员、监管机构、期刊编辑和企业代表在内的多元化国际参与者,提出了CODE-EHR的最低标准框架。为改进研究设计、提高信息透明度提供方法手段,同时为实现医疗保健数据的稳健并能够有效运用制定了技术路线图。 | Dipak Kotecha Folkert W Asselbergs Stephan Achenbach Stefan DAnker Dan Atars Colin Baigent Amitava Banerjee Birgit Beger Cunnar Brobert Barbara Casadei Cinzia Ceccarelli Martin R Cowie Filippo Crea Maureen Cronin Spiros Denaxas Andrea Derix Donna Fitzsimons Martin Fredriksson Chris PGale Georgios V Ckoutos Wim Goettsch Harry Hemingway Martin Ingvaris Adrian Jonas's Robert Kazmierski Susanne Logstrup R Thomas Lumbers Thomas F Lischer Paul McGreavy leana L Pina Lothar Roesiga Carl Steinbeisser Mats Sundgren Benoit Tyl Chislaine van Thiel Kees van Bochove Panos EVardas Tiago Villanueva Marilena Vrana Wim Weber Franz Weidinger Stephan Windecker Angela Wood Diederick E Grobbee 创新药物计划BigData@Heart联盟 欧洲心脏病协会 CODE-EHR国际共识小组 宋奇繁(译) 汪奕名(译) | 2022 | 英国医学杂志中文版2022，25，12： | 0 |
| 19 | A dual role of lysophosphatidic acid type 2 receptor(LPAR2)in nonsteroidal anti-inflammatory drug-induced mouse enteropathy显示文摘Lysophosphatidic acid(LPA)is a bioactive phospholipid mediator that has been found to ameliorate nonsteroidal anti-inflammatory drug(NSAID)-induced gastric injury by acting on lysophosphatidic acid type 2 receptor(LPAR2).In this study,we investigated whether LPAR2 signaling was implicated in the development of NSAID-induced small intestinal injury(enteropathy),another major complication of NSAID use.Wild-type(WT)and Lpar2 deficient(Lpar2^(^(^(−/−))))mice were treated with a single,large dose(20 or 30 mg/kg,i.g.)of indomethacin(IND).The mice were euthanized at 6 or 24 h after IND treatment.We showed that IND-induced mucosal enteropathy and neutrophil recruitment occurred much earlier(at 6 h after IND treatment)in Lpar2^(^(^(−/−)))mice compared to WT mice,but the tissue levels of inflammatory mediators(IL-1β,TNF-α,inducible COX-2,CAMP)remained at much lower levels.Administration of a selective LPAR2 agonist DBIBB(1,10 mg/kg,i.g.,twice at 24 h and 30 min before IND treatment)dose-dependently reduced mucosal injury and neutrophil activation in enteropathy,but it also enhanced IND-induced elevation of several proinflammatory chemokines and cytokines.By assessing caspase-3 activation,we found significantly increased intestinal apoptosis in IND-treated Lpar2^(^(^(−/−)))mice,but it was attenuated after DBIBB administration,especially in non-obese diabetic/severe combined immunodeficiency(NOD/SCID)mice.Finally,we showed that IND treatment reduced the plasma activity and expression of autotaxin(ATX),the main LPA-producing enzyme,and also reduced the intestinal expression of Lpar2 mRNA,which preceded the development of mucosal damage.We conclude that LPAR2 has a dual role in NSAID enteropathy,as it contributes to the maintenance of mucosal integrity after NSAID exposure,but also orchestrates the inflammatory responses associated with ulceration.Our study suggests that IND-induced inhibition of the ATX-LPAR2 axis is an early event in the pathogenesis of enteropathy. | Barbara Hutka Anett Várallyay Szilvia B.László András S.Tóth Bálint Scheich Sándor Paku Imre Vörös Zoltán Pós Zoltán V.Varga Derek D.Norman Andrea Balogh Zoltán Benyó Gábor Tigyi Klára Gyires Zoltán S.Zádori | 2024 | Acta Pharmacologica Sinica2024，45，2： | 0 |
| 20 | Real-world performance analysis of a novel computational method in the precision oncology of pediatric tumors显示文摘Background The utility of routine extensive molecular profiling of pediatric tumors is a matter of debate due to the high number of genetic alterations of unknown significance or low evidence and the lack of standardized and personalized decision support methods.Digital drug assignment(DDA)is a novel computational method to prioritize treatment options by aggregating numerous evidence-based associations between multiple drivers,targets,and targeted agents.DDA has been validated to improve personalized treatment decisions based on the outcome data of adult patients treated in the SHIVA01 clinical trial.The aim of this study was to evaluate the utility of DDA in pediatric oncology.Methods Between 2017 and 2020,103 high-risk pediatric cancer patients(<21 years)were involved in our precision oncology program,and samples from 100 patients were eligible for further analysis.Tissue or blood samples were analyzed by whole-exome(WES)or targeted panel sequencing and other molecular diagnostic modalities and processed by a software system using the DDA algorithm for therapeutic decision support.Finally,a molecular tumor board(MTB)evaluated the results to provide therapy recommendations.Results Of the 100 cases with comprehensive molecular diagnostic data,88 yielded WES and 12 panel sequencing results.DDA identified matching off-label targeted treatment options(actionability)in 72/100 cases(72%),while 57/100(57%)showed potential drug resistance.Actionability reached 88%(29/33)by 2020 due to the continuous updates of the evidence database.MTB approved the clinical use of a DDA-top-listed treatment in 56 of 72 actionable cases(78%).The approved therapies had significantly higher aggregated evidence levels(AELs)than dismissed therapies.Filtering of WES results for targeted panels missed important mutations affecting therapy selection.Conclusions DDA is a promising approach to overcome challenges associated with the interpretation of extensive molecular profiling in the routine care of high-risk pediatric cancers.Knowledgebase updates enable automatic interpretation of a continuously expanding gene set,a“virtual”panel,filtered out from genome-wide analysis to always maximize the performance of precision treatment planning. | Barbara Vodicska Júlia Déri Dóra Tihanyi Edit Várkondi EnikőKispéter Róbert Dóczi Dóra Lakatos Anna Dirner Mátyás Vidermann Péter Filotás Réka Szalkai-Dénes István Szegedi Katalin Bartyik Krisztina Míta Gábor Réka Simon Péter Hauser György Péter Csongor Kiss Miklós Garami István Peták | 2023 | World Journal of Pediatrics2023，19，10： | 0 |
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