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Helicobacter pylori and microRNAs:Relation with innate immunity and progression of preneoplastic conditions

World Journal of Clinical Oncology 2015年第5期6卷 111-132页

作者： Diogo Libanio Mário Dinis-Ribeiro pedro pimentel-nunes Gastroenterology Department Portuguese Oncology Institute Center for Health Technology and Services Resarch Faculty of Medicine University of Porto Department of Health Information and Decision Sciences Faculty of Medicine University of Porto Department of Physiology and Cardio- thoracic Surgery Cardiovascular Research and Development UnitFaculty of Medicine University of Porto

The accepted paradigm for intestinal-type gastric cancer pathogenesis is a multistep progression from chronic gastritis induced by Helicobacter pylori(H. pylori) to gastric atrophy, intestinal metaplasia, dysplasia and ultimately gastric cancer. The genetic and molecular mechanisms underlying disease progression are still not completely understood as only a fraction of colonized individuals ever develop neoplasia suggesting that bacterial, host and environmental factors are involved. Micro RNAs are noncoding RNAs that may influence H. pylori-related pathology through the regulation of the transcription and expression of various genes, playing an important role in inflammation, cell proliferation, apoptosis and differentiation. Indeed, H. pylori have been shown to modify micro RNA expression in the gastric mucosa and micro RNAs are involved in the immune host response to the bacteria and in the regulation of the inflammatory response. Micro RNAs have a key role in the regulation of inflammatory pathways and H. pylori may influence inflammation-mediated gastric carcinogenesis possibly through DNA methylation and epigenetic silencing of tumor suppressor micro RNAs. Furthermore, micro RNAs influenced by H. pylori also have been found to be involved in cell cycle regulation, apoptosis and epithelial-mesenchymal transition. Altogether, micro RNAs seem to have an important role in the progression from gastritis to preneoplastic conditions and neoplastic lesions and since each micro RNA can control the expression of hundreds to thousands of genes, knowledge of micro RNAs target genes and their functions are of paramount importance. In this article we present a comprehensive review about the role of micro RNAs in H. pylori gastric carcinogenesis, identifying the micro RNAs downregulated and upregulated in the infection and clarifying their biological role in the link between immune host response, inflammation, DNA methylation and gastric carcinogenesis.

关键词： Helicobacter pylori MicroRNA Gastric cancer Inflammation DNA methylation Preneoplastic conditions Stomach neoplasms Immune response

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Innate immunity and hepatocarcinoma:Can toll-likereceptors open the door to oncogenesis?

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World Journal of Hepatology 2016年第3期8卷 162-182页

作者： Jorge AndréGomes Lopes Marta Borges-Canha pedro pimentel-nunes Department of Physiology and Cardiothoracic Surgery Cardiovascular Research and Development UnitFaculty of MedicineUniversity of Porto4200-319 PortoPortugal Gastroenterology Department Portuguese Oncology Institute4200-072 PortoPortugal CINTESIS/Department of Biostatistics and Medical Informatics Faculty of MedicineUniversity of Porto4200-319 PortoPortugal

Hepatocarcinoma(HCC) is a highly prevalent cancer worldwide and its inflammatory background was established long *** studies have shown that innate immunity is closely related to the HCC *** effective innate immunity response relies on the tolllike receptors(TLR) found in several different liver cells which,through different ligands and many signaling pathways can elicit,not only a pro-inflammatory but also an oncogenic or anti-oncogenic *** aim was to study the role of TLRs in the liver oncogenesis and as a consequence their value as potential therapeutic *** performed a systematic review of PubMed searching for original articles studying the relationship between HCC and TLRs until March ***2 appears to be a fundamental stress-sensor as its absence reveals an augmented tendency to accumulate DNAdamages and to cell ***,pathways are still not fully understood as TLR2 up-regulation was also associated to enhanced ***3 has a wellknown protective role influencing crucial processes like angiogenesis,cell growth or ***4 works as an interesting epithelial-mesenchymal transition's inducer and a promoter of cell survival probably inducing HCC carcinogenesis even though an anti-cancer role has already been ***9's influence on carcinogenesis is also controversial and despite a potential anticancer capacity,a pro-tumorigenic role is more *** polymorphisms in some TLRs have been found and its influence on the risk of HCC has been *** therapeutic targets,TLRs are already in use and have a great *** conclusion,TLRs have been shown to be an interesting influence on the HCCs microenvironment,with TLR3 clearly determining an antitumour ***4 and TLR9 are considered to have a positive relationship with tumour development even though,in each of them anti-tumorigenic signals have been ***2 presents a more ambiguous role,possibly depending on the stag

关键词： Hepatocarcinoma Carcinogenesis Toll-likereceptor Innate immunity Chronic inflammation

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Clinical and pathological characterization of epstein-barr virus-associated gastric carcinomas in portugal

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World Journal of Gastroenterology 2017年第40期23卷 7292-7302页

作者： Joana Ribeiro Andreia Oliveira Mariana Malta Claudia Oliveira Fernanda Silva Ana Galaghar Luís pedro Afonso Maria Cassiano Neves Rui Medeiros pedro pimentel-nunes Hugo Sousa Molecular Oncology and Viral Pathology Group Portuguese Oncology Institute of Porto Faculty of Medicine of Porto University Department of Pathology Portuguese Oncology Institute of Porto Medical Oncology Department Portuguese Oncology Institute of Porto Instituto CUF de Oncologia Virology Service Portuguese Oncology Institute of Porto Research Department-Portuguese League Against Cancer(Liga Portuguesa Contra o Cancro-Núcleo Regional do Norte) Gastroenterology Service Portuguese Oncology Institute of Porto CINTESIS-Center for Health Technology and Services Research(Centro de Investigacao Médica Faculdade de Medicina da Universidade do Porto)

AIM To determine the prevalence of epstein-barr virus(eb V)-associated gastric carcinomas in the North Region of Portugal and to study its clinicopathological characteristics. METHODS We have performed a retrospective study including a total of 179 consecutive patients with gastric cancer(GC) submitted to gastrectomy during 2011 at the Portuguese Oncology Institute of Porto. Clinical and pathological data was collected from individual clinical records and inserted on a database with unique codification. Tumour tissues were collected from the institutional tumour bank. eb V was detected by in situ hybridization for the detection of eb V-encoded small RNAs(ebe Rs) and eb V latent proteins(LMP1 and LMP2 A) were detected by *** The analysis showed that eb V-associated gastric carcinomas(eb Va GC) represents 8.4%(15/179) of all GC cases, with a significant differential distribution among histological types(P < 0.001): 100%(3/3) of medullary carcinomas, 100%(1/1) of adenosquamous carcinoma, 8.7%(8/92) of tubular adenocarcinomas, 8.0%(2/25) of mixed carcinomas and 2%(1/51) in poorly cohesive carcinomas. The analysis revealed a higher predominance of eb Va GC in the upper third and middle(cardia, fundus and body) of the stomach(P = 0.041), a significant lower number of regional lymph nodes invasion(P = 0.025) and a tendency for better prognosis(P = 0.222). eb V latent protein expression revealed that all eb Va GC cases were LMP1-negative, nevertheless 6 cases(40%) expressed LPM2 A, which reveals that these cases show a distinct eb V-Latency profile(latency II-like).CONCLUSION eb Va GC represents 8.4% of all GC in the North Region of Portugal. The eb V-infected patients have specific clinic-pathological features that should be further explored to develop new strategies of management and treatment.

关键词： Gastric cancer Epstein-barr virus Prevalencel Epstein-barr virus-associated gastric carcinomas

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Brain scarring in infants:immunological insights from a neonatal hypoxic-ischemic encephalopathy model

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Neural Regeneration Research 2025年第10期20卷 2909-2910页

作者： pedro Moreno pimentel-Coelho Carlos Chagas Filho Biophysics Institute Federal University of Rio de JaneiroRio de JaneiroBrazil

Neonatal hypoxic-ischemic encephalopathy(HIE)is a significant cause of disability in *** brain function and accelerating neurological recovery may require a combination of neuroprotective and pro-regenerative treatments at different stages of *** the first hours after the neonatal insult are the most critical period for neuroprotection,the existence of secondary and tertiary mechanisms of brain injury offers the possibility of preventing delayed neurodegeneration in the subsequent days,weeks,or months(Levison et al.,2022).

关键词： neonatal protective hypoxic

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Helicobacter pylori-induced inflammation masks the underlying presence of low-grade dysplasia on gastric lesions

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World Journal of Gastroenterology 2020年第26期26卷 3834-3850页

作者： Alba Panarese Giovanni Galatola Raffaele Armentano pedro pimentel-nunes Enzo Ierardi Maria Lucia Caruso Francesco Pesce Marco Vincenzo Lenti Valeria Palmitessa Sergio Coletta Endrit Shahini Department of Gastroenterology and Digestive Endoscopy National Institute of Gastroenterology"S De Bellis"Research HospitalCastellana Grotte 70013Italy Department of Clinical Pathology National Institute of Gastroenterology"S De Bellis"Research HospitalCastellana Grotte 70013Italy Center for Research in Health Technologies and Information Systems Faculty of MedicinePorto 4200072Portugal Surgery and Physiology Department Faculty of Medicine of the University of PortoPorto 4200072Portugal Department of Emergency and Organ Transplantation University of BariBari 70124Italy Nephrology Section Department of Emergency and Organ TransplantationUniversity of BariBari 70124Italy First Department of Internal Medicine San Matteo Hospital FoundationUniversity of PaviaPavia 27100Italy Laboratory of Microbiology and Virology National Institute of Gastroenterology"S De Bellis"Research HospitalCastellana Grotte 70013Italy Gastroenterology Unit Institute for Cancer Research and TreatmentTurin 10121Italy

BACKGROUND Helicobacter pylori(***)infection has been associated with a long-term risk of precancerous gastric conditions(PGC)even after *** *** To investigate the efficacy of High-Resolution White-Light Endoscopy with Narrow-Band Imaging in detecting PGC,before/after *** *** We studied 85 consecutive patients with ***-related gastritis with/without PGC before and 6 mo after proven *** ***-Takemoto modified and endoscopic grading of gastric intestinal metaplasia classifications,were applied to assess the endoscopic extension of atrophy and intestinal *** histological result was considered to be the gold *** Sydney System,the Operative-Link on Gastritis-Assessment,and the Operative-Link on Gastric-Intestinal Metaplasia were used for defining histological gastritis,atrophy and intestinal metaplasia,whereas dysplasia was graded according to World Health Organization *** anti-parietal cell antibody and anti-intrinsic factor were measured when autoimmune atrophic gastritis was *** After *** eradication histological signs of mononuclear/polymorphonuclear cell infiltration and Mucosal Associated Lymphoid Tissue-hyperplasia,disappeared or decreased in 100%and 96.5%of patients respectively,whereas the Operative-Link on Gastritis-Assessment and Operative-Link on Gastric-Intestinal Metaplasia stages did not ***-Grade Dysplasia prevalence was similar on random biopsies before and after *** eradication(17.6%vs 10.6%,P=0.19),but increased in patients with visible lesions(0%vs 22.4%,P<0.0001).At a multivariate analysis,the probability for detecting dysplasia after resolution of ***-related active inflammation was higher in patients with regression or reduction of Mucosal Associated Lymphoid Tissue hyperplasia,greater alcohol consumption,and anti-parietal cell antibody and/or anti-intrinsic factor positivity[odds ratio(OR)=3.88,95%confidence i

关键词： Autoimmune gastritis Dysplasia Diagnosis Malignancy Gastric cancer Symptoms Signs

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Toll-Like Receptors as Biomarkers of Gastric Carcinogenesis:Implications for Diagnosis,Prognosis and Treatment

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Journal of Cancer Therapy 2013年第5期4卷 1037-1047页

作者： pedro pimentel-nunes Joao Bruno Soares Mário Dinis-Ribeiro Department of Physiology Cardiovascular Research&Development UnitFaculty of MedicineUniversity of PortoPortoPortugal Gastroenterology Department Portuguese Oncology InstitutePortoPortugal Gastroenterology Department Hospital de BragaBragaPortugal CIDES/CINTESIS Faculty of MedicineUniversity of PortoPortoPortugal

Toll-like receptors (TLR) are essential for Helicobacter pylori (Hp) recognition and subsequent innate and adaptive immunity responses. TLR2 appears to be the receptor responsible for most of the immunologic reaction against Hp infection. However, TLR4, TLR9 and eventually TLR5 may also have a synergic effect with TLR2 against Hp. It has been shown that gastric Hp infection increases TLR expression in the gastric mucosa. Moreover, recent studies have shown that human gastric carcinogenesis is associated not only with increased expression of TLR but also with decreased expression of their inhibitors such as Toll-Interacting Protein (TOLLIP) and peroxisome proliferator-activated receptor (PPAR)-g. Indeed, gastric dysplasia and adenocarcinoma are associated with high expression levels of TLR and low levels of TOLLIP and PPAR-g, suggesting increased activation of these receptors throughout human gastric carcinogenesis. In this article we discuss how these novels findings could be used not only for the diagnosis and prognosis of gastric lesions associated with Hp infection but also for their treatment. Specifically, we discuss the potential use of TLR agonists in addition to antibiotics to improve eradication rates of Hp and of TLR antagonists to slow the progression of gastric preneoplastic lesions. We also discuss the potential value of TLR signalling blockers and quantification of tumoral TLR expression, respectively, in the treatment and prognosis of gastric cancer. In conclusion, TLRs can be an important link between Hp and the sequence of gastric carcinogenesis and they can be used as biomarkers of gastric carcinogenesis. In this article, future lines of investigation related with these novel scientific findings are proposed and discussed.

关键词： Toll-Like Receptors Gastric Cancer TOLLIP Carcinogenesis Helicobacter pylori

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Tracheobronchial Polyflex stents for the management of benign refractory hypopharyngeal strictures

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World Journal of Gastroenterology 2012年第6期18卷 551-556页

作者： Rui Almeida Silva Nuno Mesquita pedro pimentel nunes Elisabete Cardoso Ricardo Marcos Pinto Luís Moreira Dias Department of Gastroenterology Instituto Português de Oncologia do Porto Francisco GentilR.Doutor António Bernardino de Almeida 4200-072PortoPortugal Department of Gastroenterology Centro Hospitalar do PortoLargo Prof.Abel Salazar 4099-001PortoPortugal

AIM:To describe a modified technique for placement of a tracheobronchial self-expanding plastic stent(SEPS) in patients with benign refractory hypopharyngeal strictures in order to improve dysphagia and allow stricture ***:A case series of four consecutive patients with complex hypopharyngeal strictures after combinedtherapy for laryngeal cancer,previously submitted to multiple sessions of dilation without lasting improvement,is *** patients underwent placement of a small diameter and unflared tracheobronchial *** outcome measurements were improvement of dysphagia and avoiding of repeated ***:The modified introducer system allowed an easy and technically successful deployment of the tracheobronchial Polyflex stent through the *** four patients developed complications related to stent *** patients had stent migration(one proximal and one distal),two patients developed phanryngocutaneous fistulas and all patients with stents in situ for more than 8 wk had hyperplastic tissue growth at the upper end of the *** recurrence was observed at 4 wk follow-up after stent removal in all patients CONCLUSION:Although technically feasible,placement of a tracheobronchial SEPS is associated with a high risk of *** diameter stents must be kept in place for longer than 3 mo to allow adequate time for stricture remodeling.

关键词： Larynx neoplasms Hypopharynx Strictures Dilation Stents

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Functions of nuclear factor Y in nervous system development,function and health

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Neural Regeneration Research 2025年第10期20卷 2887-2894页

作者： pedro Moreira Roger Pocock Development and Stem Cells Program Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental BiologyMonash UniversityMelbourneVICAustralia

Nuclear factor Y is a ubiquitous heterotrimeric transcription factor complex conserved across eukaryotes that binds to CCAAT boxes,one of the most common motifs found in gene promoters and *** the last 30 years,research has revealed that the nuclear factor Y complex controls many aspects of brain development,including differentiation,axon guidance,homeostasis,disease,and most recently ***,a complete understanding of transcriptional regulatory networks,including how the nuclear factor Y complex binds to specific CCAAT boxes to perform its function remains *** this review,we explore the nuclear factor Y complex’s role and mode of action during brain development,as well as how genomic technologies may expand understanding of this key regulator of gene expression.

关键词： axon guidance CCAAT boxes neuronal degeneration neuronal differentiation neuronal regeneration nuclear factor Y complex transcription factor transcriptional regulation

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Touristic urbanization and greening of coastal dune fields:A long-term assessment of a temperate sandy barrier of Argentina

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Journal of Geographical Sciences 2025年第1期35卷 206-230页

作者： GARZO pedro Andrés DADON JoséRoberto ISLA Federico Ignacio Instituto de Investigaciones Marinas y Costeras(IIMyC-CONICET/UNMDP) Av.Juan B.Justo 2550Mar del Plata7600Buenos AiresArgentina Instituto de Geología de Costas y del Cuaternario Dr.Enrique J.Schnack(IGCC-CIC/UNMDP) Funes 3350Mar del Plata7600Buenos AiresArgentina Facultad de Arquitectura Diseño y UrbanismoCentro de Investigaciones Gestión de Espacios Costeros(GEC-FADU/UBA)Universidad de Buenos AiresIntendente Güiraldes 2160Pabellón ⅢPiso 4Ciudad Autónoma de Buenos Aires1428Argentina Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET) Buenos AiresArgentina

Dune barrier systems represent highly sought-after coastal landscapes for tourism and urban development around the ***,a century ago,they were considered hazardous environments due to their great dynamic *** a result,stabilization practices were considered *** systematic introduction of fast-growing exotic trees helped stabilize the sand,making it easier for tourism urbanization to take place,but also leading to erosion *** paper aims to assess long-term changes in vegetation cover over a large temperate barrier in *** complex region includes urban resorts,afforestation zones,and protected areas.A GIS-based geospatial analysis was conducted using a large satellite database(>350 images),and the future evolution of the vegetation was *** results revealed two primary spatiotemporal patterns associated with a gradual expansion of vegetation cover,accompanied by a concurrent reduction in sandy *** 1986,the dune area comprised 75%more surface than vegetation,whereas in 2021,it represented 60%less than ***,the 2050 scenario suggests a potential 40%reduction of dunes in certain *** is necessary to enhance management actions aimed at maintaining dune mobility and ensuring local and regional sediment ***-term management strategies must focus on restoring native plant communities and controlling invasive species,and avoiding new dune fixation initiatives based on the introduction of exotic species.

关键词： nature reserves afforestation sediment balance dune management NDVI

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Kinetics of the reaction of OH radical with ethylfluoroacetate,ethyl 4,4,4-trifluorobutyrate,and butylfluoroacetate

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Journal of Environmental Sciences 2025年第5期151卷 273-283页

作者： pedro L.Lugo Vianni Straccia Mariano A.Teruel María B.Blanco Laboratorio Universitario de Química y Contaminación del Aire(L.U.Q.C.A) Institute for Research in Physical Chemistry of Córdoba(I.N.F.I.Q.C.)Department of Physical ChemistryFaculty of Chemical SciencesNational University of CórdobaUniversity CityCórdoba 5000Argentina Institute for Atmospheric and Environmental Research University of WuppertalWuppertal DE-42097Germany

Kinetics of the gas-phase reactions of•OH radicals with a series of fluoroesters were studied for the first time at 298±3 K and atmospheric *** rate coefficients were determined by in situ FTIR spectroscopy in nitrogen and GC-FID in air to monitor the decay of reactants and *** following coefficient values(in 10^(−12)cm^(3)/(molecule•sec))were obtained for ethyl fluoroacetate(EFA),ethyl 4,4,4-trifluorobutyrate(ETB),and butyl fluoroacetate(BFA),respectively:k_(1)(EFA+OH)=1.15±0.25 by FTIR and 1.34±0.23 by GC-FID;k_(2)(ETB+OH)=1.61±0.36 by FTIR and 2.02±0.30 by GC-FID;k_(3)(BFA+OH)=2.24±0.37 by *** trends were developed and correlated with the number of CH_(3)and F substituents in the fluoroester,and structure-activity relationships(SARs)calculations were *** addition,the tropospheric lifetimes of EFA,ETB,and BFA upon degradation by OH radicals were calculated to be 9,6,and 5 days,respectively,indicating that these fluorinated compounds could have a possible regional effect from the emission *** small photochemical ozone creation potentials of 9,7,and 19 were estimated for EFA,ETB,and BFA,*** GlobalWarming Potentials(GWPs)for EFA,ETB,and BFA were calculated for different time *** a 20-year time horizon,the GWPs were 1.393,0.063,and 0.062,*** the case of a 100-year time horizon,the GWPs were 0.379,0.017,and 0.017,and for a 500-year time horizon,the GWPs were 0.108,0.005,and 0.005 for EFA,ETB,and BFA.

关键词： CFC replacements sinks in situ FTIR SAR Acidification potentials Greenhouse gases

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