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Upregulation of the ApE1 and H2AX genes and miRNAs involved in DNA damage response and repair in gastric cancer

Genes & Diseases 2019年第2期6卷 176-184页

作者： Fernanda S.Manoel-Caetano ana Flávia T.Rossi gabriela Calvet de Morais Fábio Eduardo Severino ana Elizabete Silva Department of Biology UNESPSāo Paulo State UniversityCampus of Sāo Josédo Rio PretoRua Cristòvāo Colombo226515.054-000Sāo Josédo Rio PretoSāo PauloBrazil Department of Surgery and Orthopedics Faculty of MedicineUNESPSāo Paulo State UniversityCampus of BotucatuAv.Prof.Mário Rubens Guimarāes Montenegros/n18.618-687BotucatuSāo PauloBrazil

Gastric cancer remains one of the leading causes of cancer-related death worldwide,and most of the cases are associated with Helicobacter pylori *** bacterium promotes the production of reactive oxygen species(ROS),which cause DNA damage in gastric epithelial *** 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 *** v3.1.1 was used to construct the postulated miRNA:mRNA interaction *** performed by real-time quantitative pCR exhibited significantly increased levels of the ApE1(RQ=2.55,pp=0.0002)genes beyond the miR-421 and miR-605 in the gastric cancer *** addition,significantly elevated levels of miR-21,miR-24 and miR-421 were observed in diffuse-type gastric *** analysis reinforced some of the gene:gene(ATM/ATR/H2AX)and miRNA:mRNA relationships obtained also with the interaction ***,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.

关键词： DNA damage response DNA repair Gastric cancer Gene expression microRNA

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Electrocardiographic measures of repolarization dispersion and their relationships with echocardiographic indices of ventricular remodeling and premature ventricular beats in hypertension

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Journal of Geriatric Cardiology 2017年第12期14卷 717-724页

作者： ana Ciobanu Gary Tse Tong Liu Maria V Deaconu gabriela S Gheorghe Adriana M Iliesiu Ioan T Nanea Department of Internal Medicine and Cardiology Theodor Burghele Clinical Hospital Carol Davila University of Medicine and Pharmacy Bucharest Romania Department of Medicine and Therapeutics Faculty of Medicine Chinese University of Hong Kong Hong Kong China Li Ka Shing Institute of Health Sci- ences Faculty of Medicine Chinese University of Hong Kong Hong Kong China Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular disease Department of Cardiology Tianjin Institute of Cardiology Second Hospital of Tianjin Medical University Tianjin China

Objective To examine the relationship between Tpeak- Tend interval （Tpe） and Tpe/QT ratio with occurrence of ventricular premature beats （VpBs） and left ventricular remodeling in hypertension. Methods A total of 52 patients with mild to moderate essential hypertension were included, undergoing echocardiography and 24-hours Holter monitoring. Ventricular remodeling was assessed by left ventricular mass index （LVMI） using the Devereux formula and diastolic fimction by transmitral E and A wave velocities and E/A ratio. Tpe was measured in the precordial leads. The end of the T wave was set by the method of the tangent to the steepest descending slope of the T wave. Results Tpe and Tpe/QT in leads V2 （r = 0.33, p = 0.01; r = 0.27, p = 0.04 respectively） and V3 （r = 0.40, p = 0.002; r = 0.40, p = 0.003, respectively） correlated significantly with LVMI. A significant inverse relationship was observed between E/A ratio and QT （r = -0.33, p = 0.01）, Tpe in V3 （r = -0.39, p = 0.003） and Tpe/QT in V3 （r = -0.31, p = 0.02）. Tpe in V3, V5, mean Tpe and maximum Tpe with cut-offvalues of 60 ms, 59 ms, 62 ms and 71 ms, respectively, associated with the occurrence of ventricular premature beats. Conclusions The repolarization parameters Tpe interval and Tpe/QT ratio correlate with LVMI and indices of left ventricular diastolic function and show better predictive values than traditional parameters such as QT interval and QT dispersion. Lead V3 is the best lead for measuring Tpe and Tpe/QT. These ECG indices can therefore be used in clinical practice to monitor LV remodeling and predict occurrence of VpBs.

关键词： Hypertension Repolarization Tpeak-Tend Ventricular remodeling

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Characterization and strong risk association of TLR2 del-196 to-174 polymorphism and Helicobacter pylori and their influence on mRNA expression in gastric cancer

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World Journal of Gastrointestinal Oncology 2020年第5期12卷 535-548页

作者： Caroline de Matos Lourenco Manoela Dias Susi Mariah Cristina Antunes do Nascimento Vilson Serafim Junior ana paula Simedan Vila gabriela Helena Rodrigues-Flemming Eny Maria Goloni-Bertollo ana Elizabete Silva Juliana Garcia de Oliveira-Cucolo Department of Graduate-Level Research Sacred Heart UniversityBauruSao Paulo 17011-970Brazil Department of Molecular Biology Sao Josédo Rio Preto School of MedicineSao Josédo Rio PretoSao Paulo 15090-000Brazil Department of Biology Sao Paulo State UniversitySao Josédo Rio PretoSao Paulo 15054-000Brazil

BACKGROUND Toll-like receptor-2(TLR2) is responsible for recognizing Helicobacter pylori(***) and activating the immune response. polymorphisms in TLR2 may modulate gastric *** To evaluate whether the TLR2 19216 T/C(rs3804099) and TLR2-196 to-174 ins/del(rs111200466) polymorphisms contribute to gastric carcinogenesis in the Brazilian population, and to determine the influence of both polymorphisms and H. pylori infection on TLR2 mRNA *** DNA was extracted from 854 peripheral blood leukocyte or gastric tissue samples[202 gastric cancer(GC), 269 chronic gastritis(CG), and 383 control/healthy(C)]and genotyped by allele-specific pCR or restriction fragment length polymorphism(RFLp)-pCR. Quantitative polymerase chain reaction by Taq Man■ assay was used to quantify TLR2 mRNA levels in fresh gastric tissues(48 GC, 36 CG, and 14 C).RESULTS Regarding the TLR2-196 to -174 polymorphism, the ins/del and del/del genotypes were associated with a higher risk of GC by comparison with the C in all of the analyzed inheritance models(codominant, dominant, recessive, overdominant and log-additive;p paring the GC and CG groups [codominant(p p p = 0.0260), overdominant(p p protective effect in the GC group compared to the C group [dominant(p = 0.0420) and log-additive(p =0.0300)]. Regarding the association of polymorphisms with H. pylori infection,individuals infected with H. pylori and harboring the TLR2-196 to-174 ins/del polymorphism had an increased risk of gastric carcinogenesis [codominant(p =0.0120), dominant(p = 0.0051), overdominant(p = 0.0240) and log-additive(p =0.0030)], while TLR2 19216 T/C was associated with a protective effect[codominant(p = 0.0039), dominant(p p = 0.0097) and log-additive(p = 0.0021)]. TLR2 mRNA levels were sig

关键词： Toll-like receptor 2 Helicobacter pylori Gastric cancer Chronic gastritis polymorphisms Gene expression

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A fundamental(often neglected)lecture skill:presenting with credibility

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Annals of Eye Science 2017年第1期2卷 181-185页

作者： ana gabriela palis Department of ophthalmology Hospital Italiano de Buenos AiresBuenos AiresArgentina

Being credible as medical speakers is a fundamental quality to achieve. Although there are many factors that determine the credibility of a medical presenter, the way presentations are delivered (the lecture’s structure, visual aids, and the lecturer’s communication skills and engagement with the audience) will influence the effect speakers have on their audience and how credible people consider the lecturer, which will ultimately affect students’ learning. This perspective provides recommendations to increase speakers’ credibility through applying common presentation and communication principles in four domains: expertise and competence (e.g., know your audience, organize your presentation, introduce yourself, hold your arguments with evidence, avoid information overload, be prepared to answer questions), authenticity (be an accessible and honest speaker), personal presence (rehearse your presentation, get organized early, enjoy the moment), and dynamism (engage your audience, do not read your slides, explain the data, use images rather than text, avoid distracting your audience, ask and encourage questions).

关键词： Lectures health communication teaching

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Trends and topics on the science of ophthalmic education

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Annals of Eye Science 2019年第1期 150-151页

作者： ana gabriela palis Jorge E.Valdez-García Department of Ophthalmology Hospital Italiano de Buenos AiresBuenos AiresArgentina Ophthalmology and Visual Science Institute School of Medicine and Health ScienceTecnologico de MonterreyMonterreyMexico

This new focused issue of Annals of Eye Science is dedicated to the science through which the knowledge,skills and values of medicine are conveyed through generations:the science of Medical *** selected a variety of topics of interest for teachers and trainees in different stages of training;topics related to knowledge,clinical and surgical teaching,and the acquisition of professional values.

关键词： teaching education knowledge

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Faculty development for teaching and assessing residents’professionalism

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Annals of Eye Science 2019年第1期4卷 131-136页

作者： ana gabriela palis Moira Raquela Altszul Department of Ophthalmology Hospital Italiano de Buenos AiresBuenos AiresArgentina

The teaching of professionalism,a key aspect of medical competence that regulates physician’s behavior towards patients,colleagues,society,and self,should be included in the curriculum of every training *** suggest a variety of formats to teach and evaluate professionalism in residents,being role modeling,reflection,case discussions,and 360-degree assessments the most commonly ***,little is published about the need to train faculty for teaching and evaluating professionalism,or how to improve institutional culture,so that principles that are indicated to teach in theory are also fulfilled in practice.

关键词： Faculty development competencies residents education professionalism

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CYp1A1,CYp2E1 and EpHX1 polymorphisms in sporadic colorectal neoplasms

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World Journal of Gastroenterology 2016年第45期22卷 9974-9983页

作者： Glaucia Maria M Fernandes Anelise Russo Marcela Alcantara proenca Nathalia Fernanda Gazola gabriela Helena Rodrigues patrícia Matos Biselli-Chicote ana Elizabete Silva Joao Gomes Netinho érika Cristina pavarino Eny Maria Goloni-Bertollo Genetics and Molecular Biology Research Unit-UpGEM Department of Molecular Biology Sao José do Rio Preto Medical School FAMERP Departament of Biology UNESP-Sao Paulo State University Departament of Surgery and Coloproctology Service Sao José do Rio Preto Medical School FAMERP

AIM To investigate the contribution of polymorphisms in the CYp1A1, CYp2E1 and EpHX1 genes on sporadic colorectal cancer(SCRC) risk. METHODS Six hundred forty-one individuals(227 patients with SCRC and 400 controls) were enrolled in the study. The variables analyzed were age, gender, tobacco and alcohol consumption, and clinical and histopathological tumor parameters. The CYp1A1 *2A, CYp1A1 *2C CYp2E1 *5B and CYp2E1 *6 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism(pCR-RFLp). The EpHX1 Tyr113 His, EpHX1 His139 Arg and CYp1A1 *2C polymorphisms were detected by real-time pCR. Chisquared test and binary logistic regression were used in the statistical analysis. Haplotype analysis was conducted using the Haploview program, version *** Age over 6 2 years was a risk factor for SCRC development(OR = 7.54, 95%CI: 4.94-11.50, p ptible to SCRC(OR = 0.55, 95%CI: 0.35-0.85, p p2E1*5B polymorphism was associated with SCRC in the codominant(heterozygous genotype: OR = 2.66, 95%CI: 1.64-4.32, p p p p p2E1*6 polymorphism was associated with an increased SCRC risk in codominant(heterozygous genotype: OR = 2.81, 95%CI: 1.84-4.28, p polymorphic : OR = 7. 3 2, 9 5 % C I : 1.85-28.96, p p p = 0.016), overdominant(OR = 2.64, 95%CI: 1.74-4.01, p p plotype formed by the minor alleles of the CYp2E1*5B(C) and CYp2E1*6(A) polymorphisms was associated with SCRC(p = 0.002). However, the CYp1A1 *2A, CYp1A1 *2C, EpHX1 Tyr113 His and EpHX1 His139 Arg polymorphisms were not associated with *** In conclusion, the

关键词： Single-nucleotide polymorphisms Colorectal neoplasms Cytochrome p-450 CYp2E1 Cytochrome p-450 CYp1A1 Epoxide hydrolases 1

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Helicobacter pylori and corpus gastric pathology are associated with lower serum ghrelin

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World Journal of Gastroenterology 2018年第3期24卷 397-407页

作者： paula Mantero Gonzalo Sebastián Matus Rodolfo Ernesto Corti ana María Cabanne Gerardo Gabriel Zerbetto de palma Liliana Marchesi Olid María Marta piskorz Marcela Beatriz Zubillaga Mariana Andrea Janjetic Cinthia gabriela Goldman Universidad de Buenos Aires Facultad de Farmacia y BioquímicaCátedra de FísicaBuenos Aires C1113AADArgentina Hospital de Gastroenterología“Dr.Carlos Bonorino Udaondo” Sección Esófago-EstómagoBuenos Aires C1264AAAArgentina Hospital de Gastroenterología"Dr.Carlos Bonorino Udaondo” Unidad PatologíaBuenos Aires C1264AAAArgentina Universidad de Buenos Aires-CONICET Facultad de MedicinaInstituto de Microbiología y Parasitología Médica(IMPAM)Buenos Aires C1121ABGArgentina Universidad de Buenos Aires Facultad de MedicinaEscuela de NutriciónBuenos Aires C1121ABGArgentina Hospital de Clínicas“Joséde San Martín” División GastroenterologíaBuenos Aires C1120AARArgentina National Scientific and Technical Research Council(CONICET) Buenos Aires C1425FQBArgentina

AIM To evaluate the association of Helicobacter pylori(H. pylori), cag A genotype, and type of gastric pathology with ghrelin, leptin and nutritional *** Fasted dyspeptic adults(18-70 years) referred for an upper digestive endoscopy were enrolled in this crosssectional study. Height and weight were assessed for body mass index(BMI) calculation. A sociodemographic survey was administered and nutrient intake was evaluated with 24 h dietary recalls. Serum total ghrelin and leptin levels were analyzed by enzymelinked immunosorbent assay. 13 C-Urea Breath Test was performed and four gastric biopsies were obtained during endoscopy for histopathology and H. pylori DNA amplification and genotyping. Data analysis was performed using χ2, Mann-Whitney U, Kruskal-Wallis tests, Spearman's correlation and linear *** One hundred and sixty-three patients(40.8 ± 14.0 years), 98/65 females/males, were included. Overall, persistent H. pylori prevalence was 53.4%(95%CI: 45.7%-65.8%). Neither nutrient intake nor BMI differed significantly between H. pylori positive and negative groups. Serum ghrelin was significantly lower in infected patients [median 311.0 pg/m L(IQR 230.0-385.5)] than in uninfected ones [median 355.0 pg/m L(IQR 253.8-547.8)](p = 0.025), even after adjusting for BMI and gender(p = 0.03). Ghrelin levels tended to be lower in patients carrying cag A positive strains both in the antrum and the corpus; however, differences with those carrying cag A negative strains did not reach statistical significance(p = 0.50 and p = 0.49, respectively). In addition, the type and severity of gastric pathology in the corpus was associated with lower serum ghrelin(p = 0.04), independently of *** status. Conversely, leptin levels did not differ significantly between infected and uninfected patients [median 1.84 ng/m L(0.80-4.85) vs 1.84 ng/m L(0.50-5.09),(p = 0.51)]. CONCLUSION H. pylori infection and severity of gastric corpus pathology are associated with l

关键词： Helicobacter pylori cagA Ghrelin Leptin pathology

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Arylated analogues of cypronazole: fungicidal effect and activity on human fibroblasts. Docking analysis and molecular dynamics simulations

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Natural products and Bioprospecting 2022年第1期12卷 107-120页

作者： Natividad Herrera Cano Sebastian A.Andujar Cristina Theoduloz Daniel A.Wunderlin ana N.Santiago Guillermo Schmeda-Hirschmann Ricardo D.Enriz gabriela E.Feresin Instituto de Biotecnología Facultad de IngenieríaUniversidad Nacional de San JuanCONICET-CCT San JuanAv.Libertador General San Martín1109(O)5400 San JuanArgentina Facultad de Química Bioquímica y Farmacia-IMIBIO-SL(CONICET)Universidad Nacional de San LuisChacabuco 9155700 San LuisArgentina Laboratorio de Cultivo Celular Facultad de Ciencias de la SaludUniversidad de TalcaCasilla 7473460000 TalcaChile ICYTAC CONICET and Universidad Nacional de CórdobaFacultad de Ciencias QuímicasDepartamentoQuímica OrgánicaCiudad UniversitariaBv.Juan Filloy s/n5000 CórdobaArgentina INFIQC CONICET and Universidad Nacional de CórdobaFacultad de Ciencias QuímicasDepartamento Química OrgánicaCiudad UniversitariaHaya de La Torre S/N5000 CórdobaArgentina Laboratorio de Química de productos Naturales Instituto de Química de Recursos NaturalesUniversidad de TalcaCasilla 7473460000 TalcaChile

Triadimefon(TDM)and cyproconazole(CpZ)are two triazoles widely used as *** azoles were synthe-sised starting from commercial TDM and *** compounds were evaluated against phytopathogenic filamentous fungi,including Aspergillus fumigatus(AF),***(AN),***(AU),***(AJ),***(AT),Fusarium oxyspo-rum and Botrytis cinerea isolated from grapevine in the province of San Juan,*** of the synthesised compounds(1-(Biphenyl-4-yloxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one,1;2-(Biphenyl-4-yl)-3-cyclopropyl-1-(1H-1,2,4-triazol-1-yl)butan-2-ol,3;3-Cyclopropyl-2-(4’-fluorobiphenyl-4-yl)-1-(1H-1,2,4-triazol1-yl)butan-2-ol,4)presented remarkable in vitro fungicidal properties,with better effects than TDM and CpZ on some of the target *** was assessed using human lung fibroblasts *** 1,with IC50 values of 389.4μM,was less toxic towards MRC-5 human lung fibroblasts than commercial TDM(248.5μM)and CpZ(267.4μM).Docking analysis and molecular dynamics simulations suggest that the compounds present the same interaction in the binding pocket of the CYp51B enzyme and with the same amino acids as *** derivatives investigated could be considered broad-spectrum but with some selectivity towards imperfect fungi.

关键词： Azoles Antifungal cytotoxicity Conformational and electronic analysis

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patient Frailty Can Increase the Risk of Acute Kidney Injury after Cardiac Surgery: pilot Study

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World Journal of Cardiovascular Surgery 2022年第10期12卷 245-255页

作者： Sergio Soto-Hopkins José Antonio Sanchez-Lopez Erick Trujillo-Magallón Ron Leder ana gabriela Gallardo-Hernandez Unidad Médica de Alta Especialidad en Cardiología Centro Médico Nacional Siglo XXI Mexico City M&#233xico IEEE Engineering in Medicine and Biology Mexico City M&#233xico Unidad de Investigación Médica en Enfermedades Metabólicas Centro M&#233dico Nacional Siglo XXI Mexico City M&#233xico

Background: Acute kidney injury (AKI) is a severe common postoperative complication of cardiac surgery (CS). It increases the risk of mortality by up to 80%. Therefore, it is essential to have preoperative risk evaluation tools. Frailty is a marker of deterioration of physiologic systems and may be associated with AKI. purpose: The study aimed to determine the utility of frailty as a predictor of AKI after CS. Method: We enrolled 91 patients undergoing CS with cardiopulmonary bypass to determine if they had frailty before surgery and were associated with postoperative AKI. The diagnosis of postoperative AKI was based on the serum creatinine criteria of the Acute Kidney Injury Network classification up to 7 days following CS. Results: The incidence of postoperative AKI was 62% in the frail group and 21% in the non-frail group. Frailty was associated with a higher risk of AKI (relative risk [RR] = 3.00, 95% CI 1.56 - 5.77, p = 0.00). In regression models, there were associations between frailty and postoperative AKI. Conclusion: This study demonstrated that frailty could be a predictor for post-CS AKI. Therefore, frailty assessment should become an essential part of the preoperative evaluation to help the anesthesiologist to estimate the surgical risk and develop preoperative and transoperative strategies to preserve the renal function and improve the cardiac surgery outcome.

关键词： Cardiac Surgery Heart-Lung Machine Acute Kidney Injury Frailty Cardiopulmonary Bypass

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