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

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 ago.Recent studies have shown that innate immunity is closely related to the HCC carcinogenesis.An 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 response.Our aim was to study the role of TLRs in the liver oncogenesis and as a consequence their value as potential therapeutic targets.We performed a systematic review of PubMed searching for original articles studying the relationship between HCC and TLRs until March 2015.TLR2 appears to be a fundamental stress-sensor as its absence reveals an augmented tendency to accumulate DNAdamages and to cell survival.However,pathways are still not fully understood as TLR2 up-regulation was also associated to enhanced tumorigenesis.TLR3 has a wellknown protective role influencing crucial processes like angiogenesis,cell growth or proliferation.TLR4 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 observed.TLR9's influence on carcinogenesis is also controversial and despite a potential anticancer capacity,a pro-tumorigenic role is more likely.Genetic polymorphisms in some TLRs have been found and its influence on the risk of HCC has been reported.As therapeutic targets,TLRs are already in use and have a great potential.In conclusion,TLRs have been shown to be an interesting influence on the HCCs microenvironment,with TLR3 clearly determining an antitumour influence.TLR4 and TLR9 are considered to have a positive relationship with tumour development even though,in each of them anti-tumorigenic signals have been described.TLR2 presents a more ambiguous role,possibly depending on the stage of the inflammationHCC axis.

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

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Needle knife fstulotomy in flat and diverticular papillae:Is it time for redemption?

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Hepatobiliary & Pancreatic Diseases International 2022年第2期21卷 175-181页

作者： João Fernandes jorge Canena Marta Moreira Gonçalo Alexandrino Luísa Figueiredo Tarcísio Araújo Luís Lourenço David Horta Luís lopes Department of Gastroenterology Santa Luzia Hospital-Unidade Local de Saúde Alto MinhoViana do CasteloPortugal Department of Gastroenterology Professor Doutor Fernando Fonseca HospitalAmadoraPortugal Department of Gastroenterology Nova Medical School/Faculty of Medical SciencesLisbonPortugal University Center of Gastrenterology-Hospital Cuf Tejo LisbonPortugal Life and Health Sciences Research Institute(ICVS) School of MedicineUniversity of MinhoBragaPortugal ICVS/3B’s-PT Government Associate Laboratory Braga/GuimarãesPortugal

Background: European Society of Gastrointestinal Endoscopy( ESGE) recommends needle-knife fstulotomy(NKF) as the preferred precut technique in cases when standard cannulation techniques fail. Despite scarce scientifc evidence, flat and diverticular papillae are thought not to be ideal for NKF, as they are associated with poor outcomes. The present study aimed to determine the outcomes of the use of NKF in relation to flat and intradiverticular papillae. Methods: This prospective multicenter study enrolled consecutive patients, evidencing na?ve flat(group A, n = 49) or diverticular papilla(group B, n = 28), who underwent NKF after failure of standard cannulation techniques. Diverticular morphology was subdivided into intradiverticular(group B1, n = 14) and diverticular border papillae(group B2, n = 14), using a previously validated endoscopic classifcation of the major papilla. The success of biliary cannulation at initial endoscopic retrograde cholangiopancreatography(ERCP), overall biliary cannulation, overall cannulation time, and the rate of adverse events were assessed in the study. Results: The initial cannulation rates were 93.9%, 64.3% and 71.4% for group A, B1, and B2, respectively( P = 0.005);overall cannulation rates after a second ERCP were 98.0%, 92.9% and 85.7%, respectively( P = 0.134). Adverse events occurred in 11.7% of patients, with post-ERCP pancreatitis(PEP) being the most common adverse event(10.4%). Although there was a trend towards a higher incidence of PEP in flat papillae, univariate and multivariate analyses did not show any signifcant relationship between pancreatitis and trainee involvement, papillary morphology, nor overall cannulation time. Conclusions: Although flat papillae are associated with high success rates of biliary cannulation using NKF, the rate of PEP is not negligible. NKF is feasible in diverticular papillae, but it is associated with a modest success rate in the initial ERCP.

关键词： Endoscopic retrograde cholangiopancreatography Needle-knife fstulotomy Small papilla Diverticular papilla Complications

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Ca^(2+)-亚氨二醋酸金属离子亲和色谱法吸附内毒素(英文)

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色谱 2012年第11期30卷 1194-1202页

作者： andré Moreni lopes jorge Sánchez ROMEU Rolando Páez MEIRELES Gabriel Marquez PERERA Rolando Perdomo MORALES Adalberto PESSOA Lourdes Zumalacárregui CáRDENAS Department of Biochemical and Pharmaceutical Technology School of Pharmaceutical SciencesUniversity of So Paulo(FCF/USP) Purification Development Department Center for Genetic Engineering and Biotechnology(CIGB) Center for Pharmaceuticals Research and Development(CIDEM) Higher Polytechnic Institute José Antonio Echeverría(CUJAE)

Endotoxins(also known as lipopolysaccharides(LPS)) are undesirable by-products of recombinant proteins,purified from Escherichia coli.LPS can be considered stable under a wide range of temperature and pH,making their removal one of the most difficult tasks in downstream processes during protein purification.The inherent toxicity of LPS makes their removal an important step for the application of these proteins in several biological assays and for a safe parenteral administration.Immobilized metal affinity chromatography(IMAC) enables the affinity interactions between the metal ions(immobilized on the support through the chelating compound) and the target molecules,thus enabling high-efficiency separation of the target molecules from other components present in a mixture.Affinity chromatography is applied with Ca2+-iminodiacetic acid(IDA) to remove most of the LPS contaminants from the end product(more than90%).In this study,the adsorption of LPS on an IDA-Ca2+ was investigated.The adsorption Freundlich isotherm of LPS-IDA-Ca2+ provides a theoretical basis for LPS removal.It was found that LPS is bound mainly by interactions between the phosphate group in LPS and Ca2+ ligands on the beads.The factors such as pH(4.0 or 5.5) and ionic strength(1.0 mol/L) are essential to obtain effective removal of LPS for contaminant levels between endotoxin' concentration values less than100 EU/mL and 100 000 EU/mL.This new protocol represents a substantial advantage in time,effort,and production costs.

关键词： immobilized metal affinity chromatography(IMAC) lipopolysaccharides(LPS) endotoxin removal recombinant proteins isotherms protein purification

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SACI Protocol: Preliminary Guidelines for the Development of Digital Health Technologies for Clinical Trials in Brazil

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E-Health Telecommunication Systems and Networks 2022年第3期11卷 85-100页

作者： Lídia Maria Lourençön Rodrigues Agia jorge Luiz Dias Agia Rui Pedro Charters lopes Rijo Valdes Roberto Bollela Domingos Alves Department of Social Medicine Ribeir&#227 o Preto Medical School University of S&#227 o Paulo Ribeir&#227 o Preto Brazil Postgraduate Program in Production Engineering UNIP S&#227 o Paulo Brazil Polytechnic Institute of Leiria Leiria Portugal Department of Internal Medicine Ribeir&#227 o Preto Medical School University of S&#227 o Paulo Ribeir&#227 o Preto Brazil

In the last decade, evidence-based medical practice has been supported on a large scale by computerized decision support tools, aiming to reduce diagnostic and therapeutic uncertainty, complementing the actions of the health professional. With technological developments, it is now possible to consider these systems as part of clinical intervention, both for the diagnosis and treatment of diseases. The literature has described the implementation of e-health tools, that is, technological innovations in the health area such as software, applications, serious games, among others, as a strategy to improve the process and adherence to treatment. However, there is still no standardized instrument in Brazil that can be used to guide the development, from the research phase, and the implementation of these tools as a health intervention, also impacting patient outcomes. With the objective of investigating a new therapeutic and preventive form, based on intervention with a computerized system, this work proposes the creation of guidelines for the registration and implementation of e-health tools as a clinical intervention. The proposal aims to be able to assist in the reporting standardization from the development stage to the application of the e-health tool helping in the treatment of diseases, registering all the experience lived in the research and applying it in different contexts of health.

关键词： Reporting Guidelines Clinical Trials Digital Health E-Health

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Eretmochelys imbricata:Lessons to Learn from a Monitoring Program in the North of Mozambique

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Natural Resources 2017年第5期8卷 382-396页

作者： Rita Anastácio Cardoso lopes jorge Ferrao Mário jorge Pereira Departamento de Biologia e CESAM Universidade de AveiroAveiroPortugal Maluane—Cabo Delgado Conservation and Tourism PembaMozambique Universidade Pedagogica MaputoMozambique AFPR—A For Plankton Research AveiroPortugal

Monitoring programs for nesting turtles around the world have been important to build up a matrix of information for better comprehension of their behaviour and dispersion. The Western Indian Ocean has several monitoring programs that are being used to reveal migration routes, phylogenetic interconnections and nesting behaviour patterns. We determined the nesting parameters for 69 records of hawksbill turtles collected during the Vamizi Island monitoring program. We also determined carapace measurements parameters of the turtles caught by fishermen in the area and give some considerations to improve the conservation of this species. Results show that the island receives hawksbill females all year long. Vamizi is a small nesting ground for this species, with an incubation period of 60.9 ± 10.6 days and a high reproductive rate. The turtles’ carapace measurements (SCL 42.0 ± SD 9.0 cm) revealed the existence of young individuals, foraging near the island, and their vulnerability to the fishing practices. This study strongly defends the need to identify more developmental and nesting spots, to be protected near Vamizi, to establish a solid network of marine reserves and corridors in the north of the Mozambique Channel.

关键词： Eretmochelys imbricata Nesting Parameters Mozambique Channel(MZC) Network of Marine Reserves

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Improvement of the Mass Spectrometry Process on an Ion Implantation

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Open Journal of Optimization 2016年第1期5卷 31-34页

作者： José lopes jorge Rocha Luís Redondo Francisco Alegria Instituto Superior de Engenharia de Lisboa Rua Conselheiro Emídio Navarro Lisbon Portugal Instituto de Plasmas e Fusão Nuclear Instituto Superior Técnico Universidade de Lisboa Lisbon Portugal Instituto Superior Técnico and Instituto de Telecomunicações Lisbon Portugal

Mass spectrometry is an essential part of ion implantation. Therefore, in order to guarantee beam purity avoiding contamination of the implanted samples, a system was developed for the high current implanter at the Laboratory of Accelerators and Radiation Technologies (LATR) at the Instituto Superior Técnico. The system presented and discussed in this paper was developed using a LabVIEW code and uses a PC to control and display the mass spectrum. It also permits to save all data acquired for posterior analysis. In order to show some capabilities of this system, some experimental results are presented.

关键词： Ion Implanter LabVIEW Mass Spectrum

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Sex Differences in Antinociceptive Effects Induced by Gravity Stress in Rats

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Journal of Behavioral and Brain Science 2013年第2期3卷 179-187页

作者： Mari Kimoto jorge lopes Zeredo Zenro Nihei Hiromi Yamashita Kei Kaida Kazuo Toda Integrative Sensory Physiology Nagasaki University Nagasaki Japan Physiological Laboratories Japan Women’s University Tokyo Japan University of Brasilia Campus Ceilandia Brasilia Brazil

A number of studies have demonstrated that sex differentially affects responses to stress and pain. In this study, sex-related differences in pain responding were investigated in a gravity-induced analgesia model, where the effects of stressful high-gravity loading (1.5G or 2.0G for 10 min) on nociceptive behavior in male and female rats were investigated. In each rat, eight sites (nose, both forepaws, upper and lower back, both hind paws and tail) were selected to apply noxious stimuli using a von Frey-type needle stimulator. The threshold values of the withdrawal responses were measured. In order to confirm the involvement of endogenous opioids in gravity-induced antinociceptive effects, naloxone-HCl (an opioid antagonist) was used. Effective analgesic effects could be induced by strong (2.0G) gravity loading, and clear sex differences were observed. Gravity-induced analgesic effects were more effective in males than in females, indicating that males are more sensitive to stress than females judging from nociceptive modulation. Naloxone-HCl produced a more pronounced suppression of nociceptive behavior in male rats, suggesting that gravity loading may activate endogenous opioids more readily in males than in females.

关键词： Gravity Stress Sex Nociception Opioid Rat

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Patient-Reported Outcomes in Prostate Cancer: Prospective Changes Analysis for Prognosis Prediction

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Journal of Cancer Therapy 2015年第15期6卷 1238-1248页

作者： Teresa Sequeira Pedro lopes Ferreira Joana Teixeira Isabel Peres jorge Oliveira Augusta Silveira Fernando Pessoa University (UFP) Porto Portugal Centro de Estudos e Investigacao em Saúde da Universidade de Coimbra (CEISUC) Coimbra Portugal Coimbra University Coimbra Portugal Fernando Pessoa University Hospital School Porto Portugal Instituto Portugues de Oncologia do Porto (IPOP) Porto Portugal

Prostate cancer is affecting a higher proportion of male population. Health Related Quality of Life assessment can guide the development of an interdisciplinary and patient-centered care intervention. This study is aimed to assess Health Related Quality of Life in prostate cancer patients. Relationships between socio-demographic, clinical characteristics and patient-reported outcomes have been considered. Consecutive outpatients with prostate cancer, admitted at the Urology Clinic of the Instituto Português de Oncologia do Porto, were studied (n = 300). Health Related Quality of Life was assessed as part of the routine practice. The European Organisation for Research and Treatment of Cancer general questionnaire, QLQ-C30, and its specific module for prostate cancer patients, QLQ-PR25, were used. Evolution along time (elapsed since diagnosis, and up to 5 years) was considered in order to search for a prognosis prediction in prostate cancer patients. This study confirms the feasibility of a systematic Health Related Quality of Life assessment. Global Health Related Quality of Life was found to be higher 6 months after diagnosis, decreasing then until the second year after diagnosis and improving thereafter. A peak with better scores was identified at the fifth year after diagnosis. Social and physical dimensions revealed a similar pattern. Clinical significance was found 6 months and 5 years after diagnosis. The prospective analysis of Health Related Quality of Life changes is able to explore the patients’ outcomes in order to find patterns and relationships for prognosis prediction along the disease course. Such approach might promote patient confidence and thus a better cancer experience.

关键词： Oncology Prostate Cancer Health Related Quality of Life Patient-Reported Outcomes Prognosis Prediction

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A Bayesian Approach for Stable Distributions:Some Computational Aspects

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Open Journal of Statistics 2013年第4期3卷 268-277页

作者： jorge A.Achcar Silvia R.C.lopes Josmar Mazucheli Raquel R.Linhares Medical School USPRibeirao PretoBrazil Mathematical Institute UFRGSPorto AlegreBrazil Departament of Statistics UEMMaringaBrazil

In this work, we study some computational aspects for the Bayesian analysis involving stable distributions. It is well known that, in general, there is no closed form for the probability density function of stable distributions. However, the use of a latent or auxiliary random variable facilitates to obtain any posterior distribution when being related to stable distributions. To show the usefulness of the computational aspects, the methodology is applied to two examples: one is related to daily price returns of Abbey National shares, considered in [1], and the other is the length distribution analysis of coding and non-coding regions in a Homo sapiens chromosome DNA sequence, considered in [2]. Posterior summaries of interest are obtained using the OpenBUGS software.

关键词： Stable Laws Bayesian Analysis DNA Sequences MCMC Methods OpenBUGS Software

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Primary Liver Large B-Cell Lymphoma: A Rare Diagnosis

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Open Journal of Blood Diseases 2015年第1期5卷 9-12页

作者： Joana de Castro Rocha Raquel lopes Ana Rita Cruz Cristina Goncalves Joao Araujo Correia jorge Coutinho Internal Medicine Department Centro Hospitalar do PortoPortoPortugal Hematology Department Centro Hospitalar do PortoPortoPortugal

Primary liver lymphoma is extremely rare, in most of cases it is a B cell lymphoma. Usually the diagnosis is made in middle-aged individuals and most of them have a relatively short life expectancy. In this article, the authors present a case report of a 75-year-old woman with symptoms of three weeks of evolution of diffuse abdominal pain, asthenia and anorexia. The analysis showed cyto cholestasis and the radiological image with lush hepatomegaly because of a large hepatic mass. The patient started chemotherapy and actually is well twenty months after the end of the chemotherapy.

关键词： Large B Cell Lymphoma Liver Rarity

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