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New avenues for the treatment of immunotherapy-resistant pancreatic cancer

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1134-1153页

作者： Luis Guilherme de oliveira Silva Fabian Fellipe Bueno Lemos Marcel Silva Luz Samuel Luca Rocha Pinheiro Mariana dos Santos Calmon gabriel Lima Correa Santos gabriel Reis Rocha Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

Pancreatic cancer(PC)is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide.However,due to its complexity,it ranks 7th in the list of the most lethal cancers worldwide.The pathogenesis of PC involves several complex processes,including familial genetic factors associated with risk factors such as obesity,diabetes mellitus,chronic pancreatitis,and smoking.Mutations in genes such as KRAS,TP53,and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and,consequently,cancer.In this context,some therapies are used for PC,one of which is immunotherapy,which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy efficiency.It is therefore clear that the tumor microenvironment(TME)has a huge impact on the resistance process,since cellular and non-cellular elements create an immunosuppressive environment,characterized by a dense desmoplastic stroma with cancerassociated fibroblasts,pancreatic stellate cells,extracellular matrix,and immunosuppressive cells.Linked to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells,resulting in a shortage of CD8+T cells and limited expression of activation markers such as interferon-gamma.In this way,finding new strategies that make it possible to manipulate resistance mechanisms is necessary.Thus,techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance,the use of genetic manipulation in specific regions,such as microRNAs,the modulation of extrinsic and intrinsic factors associated with T cells,and,above all,therapeutic models that combine these modulation techniques constitute the promising future of PC therapy.Thus,this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating this process,resulting in a more efficient therapy

关键词： Pancreatic cancer Immunotherapy Resistance Tumor microenvironment manipulation Combined immunotherapy

Urea breath test for Helicobacter pylori infection in adult dyspeptic patients: A meta-analysis of diagnostic test accuracy

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World Journal of Gastroenterology 2024年第6期30卷 579-598页

作者： Fabian Fellipe Bueno Lemos Caroline Tianeze de Castro Marcel Silva Luz gabriel Reis Rocha gabriel Lima Correa Santos Luís Guilherme de oliveira Silva Mariana Santos Calmon Cláudio Lima Souza Ana Carla Zarpelon-Schutz Kádima Nayara Teixeira Dulciene Maria de Magalhães Queiroz Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil Instituto de Saúde Coletiva Universidade Federal da BahiaSalvador 40110040BahiaBrazil Campus Toledo Universidade Federal do ParanáToledo 85919-899ParanáBrazil Laboratory of Research in Bacteriology UFMGBelo Horizonte 30130-100Minas GeraisBrazil

BACKGROUND Helicobacter pylori(H.pylori)infection has been well-established as a significant risk factor for several gastrointestinal disorders.The urea breath test(UBT)has emerged as a leading non-invasive method for detecting H.pylori.despite numerous studies confirming its substantial accuracy,the reliability of UBT results is often compromised by inherent limitations.These findings underscore the need for a rigorous statistical synthesis to clarify and reconcile the diagnostic accuracy of the UBT for the diagnosis of H.pylori infection.AIM To determine and compare the diagnostic accuracy of 13C-UBT and 14C-UBT for H.pylori infection in adult patients with dyspepsia.METHODS We conducted an independent search of the PubMed/MEDLINE,EMBASE,and Cochrane Central databases until April 2022.Our search included diagnostic accuracy studies that evaluated at least one of the index tests(^(13)C-UBT or ^(14)C-UBT)against a reference standard.We used the QUADAS-2 tool to assess the methodo-logical quality of the studies.We utilized the bivariate random-effects model to calculate sensitivity,specificity,positive and negative test likelihood ratios(LR+and LR-),as well as the diagnostic odds ratio(DOR),and their 95%confidence intervals.We conducted subgroup analyses based on urea dosing,time after urea administration,and assessment technique.To investigate a possible threshold effect,we conducted Spearman correlation analysis,and we generated summary receiver operating characteristic(SROC)curves to assess heterogeneity.Finally,we visually inspected a funnel plot and used Egger’s test to evaluate publication bias.endorsing both as reliable diagnostic tools in clinical practice.CONCLUSION In summary,our study has demonstrated that ^(13)C-UBT has been found to outperform the ^(14)C-UBT,making it the preferred diagnostic approach.Additionally,our results emphasize the significance of carefully considering urea dosage,assessment timing,and measurement techniques for both tests to enhance diagnostic precision.Nevertheless,it is cru

关键词： Helicobacter pylori Urea breath test Diagnosis Diagnostic test accuracy Meta-analysis

Immune pathway through endometriosis to ovarian cancer

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World Journal of Clinical Oncology 2024年第4期15卷 496-522页

作者： Mariana Santos Calmon Fabian Fellipe Bueno Lemos Marcel Silva Luz Samuel Luca Rocha Pinheiro Luis Guilherme de oliveira Silva gabriel Lima Correa Santos gabriel Reis Rocha Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

Endometriosis is an estrogen-dependent inflammatory disease,defined by the presence of functional endometrial tissue outside of the uterine cavity.This disease is one of the main gynecological diseases,affecting around 10%-15%women and girls of reproductive age,being a common gynecologic disorder.Although endometriosis is a benign disease,it shares several characteristics with invasive cancer.Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer,representing an earlier stage of neoplastic processes.This is particularly true for women with clear cell carcinoma,low-grade serous carcinoma and endometrioid.However,the carcinogenic pathways between both pathologies remain poorly understood.Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers(EAOCs)via pathways associated with oxidative stress,inflammation,and hyperestrogenism.This article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis,specifically focusing on the complex relationship between the immune response to endometriosis and cancer,including the molecular mechanisms and their ramifications.Examining recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.

关键词： Ovarian neoplasms Endometriosis Endometriosis-associated ovarian cancers Immune response Immunotherapy

Rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease

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World Journal of Hepatology 2024年第1期16卷 75-90页

作者： Matheus Truccolo Michalczuk Larisse Longo Melina Belén Keingeski Bruno de Souza Basso gabriel Tayguara Silveira Guerreiro Jessica T Ferrari JoséEduardo Vargas Cláudia P oliveira Carolina Uribe-Cruz Carlos Thadeu Schmidt Cerski Eduardo Filippi-Chiela Mário ReisÁlvares-da-Silva Division of Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Graduate Program in Gastroenterology and Hepatology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Experimental Laboratory of Hepatology and Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Laboratory of Inflammatory and Neoplastic Cells Universidade Federal do ParanáParaná81530900Brazil department of Gastroenterology(LIM07) Faculdade de Medicina da Universidade de São PauloSão Paulo 01246903Brazil Facultad de Ciencias de la Salud Universidad Católica de las MisionesPosadasMisiones 3300Argentina Unit of Surgical Pathology Hospital de Clinicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Center of Biotechnology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil department of Morphological Sciences Universidade Federal do Rio Grande do SulPorto Alegre 90.050-170Rio Grande do SulBrazil Conselho Nacional de desenvolvimento Científico e Tecnológico(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)ResearcherBrasília 71.605-001Brazil

BACKGROUND Prevalence of hepatocellular carcinoma(HCC)is increasing,especially in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD).AIM To investigate rifaximin(RIF)effects on epigenetic/autophagy markers in animals.METHODS Adult Sprague-Dawley rats were randomly assigned(n=8,each)and treated from 5-16 wk:Control[standard diet,water plus gavage with vehicle(Veh)],HCC[high-fat choline deficient diet(HFCD),diethylnitrosamine(deN)in drinking water and Veh gavage],and RIF[HFCD,deN and RIF(50 mg/kg/d)gavage].Gene expression of epigenetic/autophagy markers and circulating miRNAs were obtained.RESULTS All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis,and cirrhosis,but three RIF-group did not develop HCC.Comparing animals who developed HCC with those who did not,miR-122,miR-34a,tubulin alpha-1c(Tuba-1c),metalloproteinases-2(Mmp2),and metalloproteinases-9(Mmp9)were significantly higher in the HCC-group.The opposite occurred with Becn1,coactivator associated arginine methyltransferase-1(Carm1),enhancer of zeste homolog-2(Ezh2),autophagy-related factor LC3A/B(Map1 Lc3b),and p62/sequestosome-1(p62/SQSTM1)-protein.Comparing with controls,Map1 Lc3b,Becn1 and Ezh2 were lower in HCC and RIF-groups(P0.05).miR-122 was higher in HCC,and miR-34a in RIF compared to controls(P0.05).CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis through epigenetic modulation in a rat model of MASLD

关键词： Animal model Autophagy Epigenetic Hepatocellular carcinoma Metabolic dysfunction-associated steatotic liver disease Rifaximin

Enhancement of the Antigenotoxic and Antioxidant Actions of Eugenol from Spice Clove and the Stabilizer Gum Arabic on Colorectal Carcinogenesis

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Food and Nutrition Sciences 2024年第1期15卷 71-100页

作者： Nayanna de oliveira Ramos Melo Lucas gabriel da Costa Marques Humberto Maia Costa Neto Matheus de Sousa Silva Francisco Vagnaldo Fechine Jamacaru Bruno Coêlho Cavalcanti Antônio Adailson de Sousa Silva Conceição Aparecida Dornelas Postgraduate Program in Medical-Surgical Sciences School of Medicine Federal University of Ceará Fortaleza Brazil School of Medicine Federal University of Ceará Fortaleza Brazil Nucleus of Research and development of Medicines (NPDM) Laboratory of Pharmacology and Preclinical Research School of Medicine Federal University of Ceará Fortaleza Brazil Nucleus for Research and development of Medicines (NPDM) National Laboratory of Experimental Oncology Federal University of Ceará Fortaleza Brazil Postgraduate Program in Pathology and Medical-Surgical Sciences School of Medicine Federal University of Ceará Fortaleza Brazil

Spices are defined as any aromatic condiment of plant origin used to alter the flavor and aroma of foods. Besides flavor and aroma, many spices have antioxidant activity, mainly related to the presence in cloves of phenolic compounds, such as flavonoids, terpenoids and eugenol. In turn, the most common uses of gum arabic are in the form of powder for addition to soft drink syrups, cuisine and baked goods, specifically to stabilize the texture of products, increase the viscosity of liquids and promote the leavening of baked products (e.g., cakes). Both eugenol, extracted from cloves, and gum arabic, extracted from the hardened sap of two species of the Acacia tree, are dietary constituents routinely consumed virtually throughout the world. Both of them are also widely used medicinally to inhibit oxidative stress and genotoxicity. The prevention arm of the study included groups: Ia, IIa, IIIa, Iva, V, VI, VII, VIII. Once a week for 20 weeks, the controls received saline s.c. while the experimental groups received DMH at 20 mg/kg s.c. During the same period and for an additional 9 weeks, the animals received either water, 10% GA, EUG, or 10% GA + EUG by gavage. The treatment arm of the study included groups Ib, IIb, IIIb e IVb, IX, X, XI, XII). Once a week for 20 weeks, the controls received saline s.c. while the experimental groups received DMH at 20 mg/kg s.c. During the subsequent 9 weeks, the animals received either water, 10% GA, EUG or 10% GA + EUG by gavage. The novelty of this study is the investigation of their use alone and together for the prevention and treatment of experimental colorectal carcinogenesis induced by dimethylhydrazine. Our results show that the combined use of 10% gum arabic and eugenol was effective, with antioxidant action in the colon, as well as reducing oxidative stress in all colon segments and preventing and treating genotoxicity in all colon segments. Furthermore, their joint administration reduced the number of aberrant crypts and the number of aberrant crypt foci (ACF) in the dis

关键词： Eugenol Gum Arabic Carcinogenesis Oxidative Stress Genotoxicity

Measuring the density of the fissula antefenestram and the section of the basal turn of the cochlea:Are they useful in the radiological diagnosis of otosclerosis?

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Journal of Otology 2022年第2期17卷 84-89页

作者： Lucas Resende Lucinda Mangia gabriel Lucca de oliveira Salvador Bettina Carvalho Rogerio Hamerschmidt department of Otolaryngology Head and Neck SurgeryHospital de Clínicas da Universidade Federal do ParanaGeneral Carneiro st181CuritibaBrazil department of Imaging and Radiology Head and Neck SurgeryHospital de Clínicas da Universidade Federal do ParanaGeneral Carneiro st181CuritibaBrazil

Introduction:The role of objective parameters in terms of improvement of the accuracy of highresolution computed tomography(HRCT)of the temporal bone in the diagnosis of otosclerosis remains unclear.Objectives:To investigate the relationship between the density of the fissula antefenestram(FAF)and of the width of the transversal section of the basal turn of the cochlea(BTC),and the diagnosis of otosclerosis.Methods:This is a retrospective study in which preoperative HRCT data from ears of patients submitted to stapedotomy due to otosclerosis(case group)were evaluated.For the control group,normal hearing ears having undergone HRCT for other purposes were included.Case and control HRCT images were objectively assessed by an experienced blinded radiologist.During this evaluation,measurements of the relative radiological density of the FAF and of the transversal section of the BTC were obtained.The results were compared between the groups.Also,a receiver operating characteristic curve was created and the area under the curve(AUC)was calculated for each variable.Significance level was set at.05.Results:40 ears were included in each group.Case ears presented reduced values for the relative radiological density on the FAF(p-valuedensity on the FAF and narrower BTC.The relative density of the FAF also shows a great diagnostic power in the context of this disease.

关键词： Otosclerosis Computed tomography Imaging diagnosis

Night and day at the beach: Relating social life to location and infrastructure in a Brazilian city

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Frontiers of Architectural Research 2022年第6期11卷 1177-1192页

作者： Lucy Donegan gabriel de oliveira Madruga Natália Vale Carneiro departamento de Arquitetura e Urbanismo Federal University of ParaíbaJoão PessoaParaíbaBrazil

Brazilian city beaches are public spaces favoring citizens well-being.Urban studies relate built form and infrastructure with urban vitality and coastal studies underline uses as important for beach management,yet few researches relate form and infrastructure with beach uses.Understanding daily life as essential for public spaces and that spatial form relates with uses,this paper assesses time-based relationships between built and natural physical attributes and social life on the beaches of João Pessoa,a coastal city in North-east Brazil.Physical attributes are investigated at city scale-beach type,street network centrality and topography-and seafront scale-land uses,public/private interfaces,public infrastructure,beach sections and water quality.Beach social life was surveyed online,enquiring peoples’beach choice,visiting time and place,activities and evaluation.Infrastructure and street network follow topography and help configure shore and promenade for different landscapes.More central beaches have diverse land uses,well-equipped promenades and lighting and were popular night and day,while less central beaches had less infrastructure and were visited only by day.Findings highlight how physical attributes facilitate uses and,together with peoples’evaluation,can inform urban beach design and planning.

关键词： Public space Social life Built environment Beaches Public infrastructure

Behavior of wood basic density according to environmental variables

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Journal of Forestry Research 2022年第2期33卷 497-505页

作者： gabriel Marcos Vieira oliveira JoséMárcio de Mello Carlos Rogério de Mello JoséRoberto Soares Scolforo Eder Pereira Miguel Thiago Campos Monteiro Brazil Institute of Agricultural and Forestry defense of Espírito Santo(IDAF) Av.Lourival Lugon Moulinnº300CentroJerônimo MonteiroES CEP:29.550-000Brazil department of Forestry Sciences Universidade Federal de Lavras-UFLACaixa Postal 3037LavrasMG CEP:37.200-000Brazil Engineering department Universidade Federal de Lavras-UFLACaixa Postal 3037LavrasMG CEP:37.200-000Brazil Forestry Engineering department Faculdade de TecnologiaUniversity of Brasilia-UnBCampus Universitário Darcy RibeiroCaixa Postal 4357Asa Norte-BrasíliaDF CEP:70910-900Brazil department of Forestry Engineering and Technology Universidade Federal do Paraná-UFPRAv.Pref.Lothário Meissner632Jardim BotânicoCuritibaPR CEP:80.210-170Brazil

The relationships between climate conditions and wood density in tropical forests are still poorly understood.To quantify spatial dependence of wood density in the state of Minas Gerais(MG,Brazil),map spatial distribution of density,and correlate density with climate variables,we extracted data from the Forest Inventory of Minas Gerais for 1988 trees scaled throughout the territory and measured wood density of discs removed from the trees.Environmental variables were extracted from the database of the Ecological-Economic Zoning of Minas Gerais.For spatial analysis,tree densities were measured at 44 georeferenced sampling points.The data were subjected to exploratory analysis,variography,cross-validation,model selection,and ordinary kriging.The relationships between wood density and environmental variables were calculated using dispersion matrices,linear correlation,and regression.Wood density proved to be highly spatially dependent,reaching a correlation of 96%,and was highly continuous over a distance of 228 km.The distribution of wood density followed a continuous gradient of 514-659 kg m^(−3),enabling corre-lation with environment variables.density was correlated with mean annual precipitation(−0.57),temperature(0.63),and evapotranspiration(0.83).Geostatistical methods proved useful in predicting wood density in native tropical forests with different climate conditions.Our results confirmed the sensitivity of wood density to climate change,which could affect future carbon stock in forests.

关键词： Biomass Climate variables Geostatistics Hardwood Forest inventory Minas Gerais

The role of environmental temperature on movement patterns of giant anteaters

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Integrative Zoology 2022年第2期17卷 285-296页

作者： Aline GIROUX Zaida ORTEGA Alessandra BERTASSONI Arnaud Léonard Jean deSBIEZ Danilo KLUYBER gabriel Favero MASSOCATO Guilherme de MIRANDA Guilherme MOURÃO Luciana SURITA Nina ATTIAS Rita de Cassia BIANCHI Vinícius Peron de oliveira GASPAROTTO Luiz Gustavo Rodrigues oliveira-SANTOS Ecology department Federal University of Mato Grosso do Sul(UFMS)Campo GrandeMato Grosso do SulBrazil Post Graduate Program of Ecology and Evolution Federal University of Goiás(UFG)GoiâniaGoiásBrazil Institute of Research and Conservation of Anteaters in Brazil(PROJETO TAMANDUÁ) ParnaíbaPiauíBrazil Institute for the Conservation of Wild Animals(ICAS) Campo GrandeMato Grosso do SulBrazil Royal Zoological Society of Scotland(RZSS) MurrayfieldEdinburghUK Institute for Ecological Research(IPÊ) NazaréPaulistaSão PauloBrazil Naples Zoo at Caribbean Gardens NaplesFloridaUSA The Houston Zoo HoustonTexasUSA National Institute of Criminalistics-Federal Police BrasíliaBrazil Embrapa Pantanal CorumbáMato Grosso do SulBrazil Natural Resources Graduate Program(PRONAT)-Federal University of Roraima(UFRR) Boa VistaRoraimaBrazil Animal Biology Graduate Program Federal University of Mato Grosso do Sul(UFMS)Campo GrandeMato Grosso do SulBrazil Animal Biology department São Paulo State University(UNESP)São Josédo Rio PretoSão PauloBrazil department of Preventive Veterinary Medicine and Animal Health School of Veterinary MedicineUniversity of São Paulo(USP)São PauloSPBrazil Brazilian Institute for Conservation Medicine(TRÍAde) RecifePernambucoBrazil

Mammals can show conspicuous behavioral responses to thermal variation,including changes in movement patterns.We used an integrative approach to understand how environmental temperature can drive the movement behavior of a mammal with low capacity for physiological thermoregulation,the giant anteater(Myrmecophaga tridactyla).We tracked 52 giant anteaters in 7 areas throughout the Brazilian savannah.We estimated the distance moved,area used,use of forest areas,and mean environmental temperature for each monitoring day of each individual.We modeled these data with Mixed Structural Equations—considering the possible interactions between our variables and controlling for sex and body mass.Giant anteaters reduced displacement and increased forest use with decreasing environmental temperature,probably because of their low body heat production.It is possible that they reduce distance moved and area used by reducing the duration of activity.With decreasing temperature,forest habitats become warmer than open ones,besides buffer rain and chilly winds.Reducing displacement and using forests are important strategies to reduce body heat loss and the energetic costs of thermoregulation.However,decreasing movement can limit food access and,consequently,fitness.Therefore,we highlight the importance of forests as thermal shelters.With increasing frequency and intensity of extreme weather events,we showed the need to preserve forest patches to offer suitable conditions for tropical mammals’behavioral thermoregulation.In this context,policies favoring deforestation on Brazilian territory are especially worrisome.Finally,we emphasize the need of integrative approaches to understand the complex interactions between organisms and the environment.

关键词： behavioral thermoregulation biologging habitat use mixed structural equations movement ecology