Helicobacter pylori cag pathogenicity island-positive strains induce syndecan-4 expression in gastric epithelial cells

Helicobacter pylori is recognized as the main cause of gastritis and is associated with gastric carcinogenesis. Syndecan-4 represents the major source of heparan sulfate (HS) in the gastric cells. HS proteoglycans expressed on the cell surface constitute targets for H. pylori at the early stage of infection. The aim of this study was to determine whether H. pylori induction of syndecan-4 expression is affected by the virulence characteristics of the infecting strain, namely the cytotoxic-associated gene (cag) pathogenicity island (PAI). We observed that individuals infected with highly pathogenic H. pylori strains express syndecan-4 in the foveolar epithelium of the gastric mucosa. The association between the cagPAI status of the infecting strain and syndecan-4 expression was further demonstrated by infection of gastric epithelial cell lines with a panel of cagPAI+ and cagPAI- H. pylori strains, showing that expression of syndecan-4 was significantly increased in response to infection with the highly pathogenic strains. Moreover, infection of gastric cells with cagA and cagE mutant strains further confirmed that syndecan-4 induction is dependent on an intact cagPAI. The present study shows that highly pathogenic H. pylori strains induce syndecan-4 expression, both in human gastric mucosa and in gastric cell lines, in a cagPAI-dependent manner. © 2009 Federation of European Microbiological Societies

Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy

High risk of recurrence/progression bladder tumours is treated with Bacillus Calmette-Guérin (BCG) immunotherapy after complete resection of the tumour. Approximately 75% of these tumours express the uncommon carbohydrate antigen sialyl-Tn (Tn), a surrogate biomarker of tumour aggressiveness. Such changes in the glycosylation of cell-surface proteins influence tumour microenvironment and immune responses that may modulate treatment outcome and the course of disease. The aim of this work is to determine the efficiency of BCG immunotherapy against tumours expressing sTn and sTn-related antigen sialyl-6-T (s6T). METHODS: In a retrospective design, 94 tumours from patients treated with BCG were screened for sTn and s6T expression. In vitro studies were conducted to determine the interaction of BCG with high-grade bladder cancer cell line overexpressing sTn. RESULTS: From the 94 cases evaluated, 36 had recurrence after BCG treatment (38.3%). Treatment outcome was influenced by age over 65 years (HR=2.668; (1.344-5.254); P=0.005), maintenance schedule (HR=0.480; (0.246-0.936); P=0.031) and multifocality (HR=2.065; (1.033-4.126); P=0.040). sTn or s6T expression was associated with BCG response (P=0.024; P<0.0001) and with increased recurrence-free survival (P=0.001). Multivariate analyses showed that sTn and/or s6T were independent predictive markers of recurrence after BCG immunotherapy (HR=0.296; (0.148-0.594); P=0.001). In vitro studies demonstrated higher adhesion and internalisation of the bacillus to cells expressing sTn, promoting cell death. CONCLUSION: s6T is described for the first time in bladder tumours. Our data strongly suggest that BCG immunotherapy is efficient against sTn- and s6T-positive tumours. Furthermore, sTn and s6T expression are independent predictive markers of BCG treatment response and may be useful in the identification of patients who could benefit more from this immunotherapy

Anti-cancer drug validation: the contribution of tissue engineered models

Abstract Drug toxicity frequently goes concealed until clinical trials stage, which is the most challenging, dangerous and expensive stage of drug development. Both the cultures of cancer cells in traditional 2D assays and animal studies have limitations that cannot ever be unraveled by improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. Considering the NCI60, a panel of 60 cancer cell lines representative of 9 different cancer types: leukemia, lung, colorectal, central nervous system (CNS), melanoma, ovarian, renal, prostate and breast, we propose to review current Bstate of art^ on the 9 cancer types specifically addressing the 3D tissue models that have been developed and used in drug discovery processes as an alternative to complement their studyThis article is a result of the project FROnTHERA (NORTE-01-0145-FEDER-000023), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This article was also supported by the EU Framework Programme for Research and Innovation HORIZON 2020 (H2020) under grant agreement n° 668983 — FoReCaST. FCT distinction attributed to Joaquim M. Oliveira (IF/00423/2012) and Vitor M. Correlo (IF/01214/2014) under the Investigator FCT program is also greatly acknowledged.info:eu-repo/semantics/publishedVersio

Wound dressings for a proteolytic-rich environment

Wound dressings have experienced continuous and significant changes over the years based on the knowledge of the biochemical events associated with chronic wounds. The development goes from natural materials used to just cover and conceal the wound to interactive materials that can facilitate the healing process, addressing specific issues in non-healing wounds. These new types of dressings often relate with the proteolytic wound environment and the bacteria load to enhance the healing. Recently, the wound dressing research is focusing on the replacement of synthetic polymers by natural protein materials to delivery bioactive agents to the wounds. This article provides an overview on the novel protein-based wound dressings such as silk fibroin keratin and elastin. The improved properties of these dressings, like the release of antibiotics and growth factors, are discussed. The different types of wounds and the effective parameters of healing process will be reviewed

Glycophenotypic Alterations Induced by Pteridium aquilinum in Mice Gastric Mucosa: Synergistic Effect with Helicobacter pylori Infection

The bracken fern Pteridium aquilinum is a plant known to be carcinogenic to animals. Epidemiological studies have shown an association between bracken fern exposure and gastric cancer development in humans. The biological effects of exposure to this plant within the gastric carcinogenesis process are not fully understood. In the present work, effects in the gastric mucosa of mice treated with Pteridium aquilinum were evaluated, as well as molecular mechanisms underlying the synergistic role with Helicobacter pylori infection. Our results showed that exposure to Pteridium aquilinum induces histomorphological modifications including increased expression of acidic glycoconjugates in the gastric mucosa. The transcriptome analysis of gastric mucosa showed that upon exposure to Pteridium aquilinum several glycosyltransferase genes were differently expressed, including Galntl4, C1galt1 and St3gal2, that are mainly involved in the biosynthesis of simple mucin-type carbohydrate antigens. Concomitant treatment with Pteridium aquilinum and infection with Helicobacter pylori also resulted in differently expressed glycosyltransferase genes underlying the biosynthesis of terminal sialylated Lewis antigens, including Sialyl-Lewisx. These results disclose the molecular basis for the altered pattern of glycan structures observed in the mice gastric mucosa. The gene transcription alterations and the induced glycophenotypic changes observed in the gastric mucosa contribute for the understanding of the molecular mechanisms underlying the role of Pteridium aquilinum in the gastric carcinogenesis process

Perfil epidemiológico de acidentes com material biológico entre estudantes de medicina em um pronto-socorro cirúrgico

OBJECTIVE: To evaluate the accidents with biological material among medical students interning in a trauma emergency room and identify key related situations, attributed causes and prevention. METHODS: we conducted a study with a quantitative approach. Data were collected through a questionnaire applied via internet, with closed, multiple-choice questions regarding accidents with biological material. The sample comprised 100 students. RESULTS: thirty-two had accidents with biological material. Higher-risk activities were local anesthesia (39.47%), suture (18.42%) and needle recapping (15.79%). The main routes of exposure to biological material were the eyes or mucosa, with 34%, and syringe needle puncture, with 45%. After contamination, only 52% reported the accident to the responsible department. CONCLUSION: The main causes of accidents and routes of exposure found may be attributed to several factors, such as lack of training and failure to use personal protective equipment. Educational and preventive actions are extremely important to reduce the incidence of accidents with biological materials and improve the conduct of post-exposure. It is important to understand the main causes attributed and situations related, so as general and effective measures can be applied.OBJETIVO: avaliar os acidentes com material biológico entre estudantes de medicina estagiando em um pronto-socorro de trauma e identificar as principais situações relacionadas, causas atribuídas e prevenção. MÉTODOS: estudo com abordagem quantitativa. Os dados foram coletados através de um questionário, aplicado via internet, contendo perguntas fechadas de escolha múltipla, referentes a acidentes com material biológico. A amostra obtida foi 100 estudantes. RESULTADOS: trinta e dois se acidentaram com materiais biológicos. As atividades de maior risco foram anestesia local (39,47%), sutura (18,42%) e recapeamento de agulha (15,79%). As principais vias de exposição ao material biológico foram contato com olho ou mucosa, com 34%, através de seringa com agulha com 45%. Após a contaminação, apenas 52% notificaram o acidente ao setor responsável. CONCLUSÃO: as principais causas de acidente encontradas e vias de exposição podem ser atribuídas a diversos fatores, como falta de treinamento e ao não uso de equipamentos de proteção individual. Ações preventivas e educativas são de extrema importância para diminuir a incidência dos acidentes com materiais biológicos e melhorar a conduta pós-exposição. É preciso entender as principais causas atribuídas e situações relacionadas a fim de implantar medidas gerais e eficazes.Universidade Estadual Paulista Júlio de Mesquita FilhoUniversidade PositivoUniversidade Federal do ParanáUniversidade Estadual Paulista Júlio de Mesquita Filh

Being a nursing teacher, woman and mother: showing the experience in the light of social phenomenology

The trajectory of this study was focused on understanding the experience of being a nursing teacher, woman and mother and reconciling work, motherhood and other daily activities. Participants were 11 women, mothers, teachers at higher education Institutions. Social Phenomenology was adopted for the analysis. The context of meanings was evidenced by categories: Difficulty in performing multiple activities; care of oneself and conciliation of social roles. Women give priority to being a mother, so that they have less time to take care of themselves. In spite of desiring to invest in teaching, they expect to have more time available to be in touch with their children and partner. This study showed that the professional and personal worlds need an interface, which allows for co-existence between the different roles women play in society.La trayectoria de este estudio se dirigió para la comprensión del ser docente de enfermería, mujer y madre, que debe conciliar la vida profesional, la maternidad y demás actividades de lo cotidiano. Participaron 11 mujeres, madres, y docentes de instituciones de enseñanza superior. Fue adoptada la Fenomenología Social para el análisis. El contexto de significados fue evidenciado a partir de las categorías: Dificultad en el desempeño de multiplicidad de actividades, Cuidado de sí misma, y Conciliación de los papeles sociales. Las mujeres le dan prioridad al ser madre, disponiendo de poco tiempo para el cuidado de sí misma; a pesar de que tengan el deseo de hacer inversiones en la carrera docente, tienen la expectativa de tener mayor disponibilidad de tiempo para la convivencia con los hijos y con el compañero. El estudio mostró que los universos, profesional y personal, necesitan de un medio de comunicación que posibilite una convivencia entre los diversos papeles ejercidos por la mujer en la sociedad.A trajetória deste estudo voltou-se para a compreensão do ser docente de enfermagem, mulher e mãe ao conciliar a vida profissional, a maternidade e demais atividades do cotidiano. Participaram 11 mulheres, mães, docentes de instituições de ensino superior. Foi adotada a fenomenologia social para análise. O contexto de significados foi evidenciado a partir das categorias: dificuldade no desempenho de multiplicidade de atividades; cuidado de si mesma e conciliação dos papéis sociais. As mulheres priorizam o ser mãe, dispondo de pouco tempo para o cuidado de si mesma; e, embora tenham o desejo de investir na carreira docente, têm a expectativa de ter maior disponibilidade de tempo para o convívio com os filhos e com o companheiro. O estudo mostrou que os universos, profissional e pessoal, necessitam de interface que possibilite a convivência entre os diversos papéis exercidos pela mulher na sociedade