Gastric Cancer: The Microbiome Beyond Helicobacter pylori.

Gastric cancer remains an important global health burden. Helicobacter pylori is the major etiological factor in gastric cancer, infecting the stomach of almost half of the population worldwide. Recent progress in microbiome research offered a new perspective on the complexity of the microbial communities of the stomach. Still, the role of the microbiome of the stomach beyond H. pylori in gastric carcinogenesis is not well understood and requires deeper investigation. The gastric bacterial communities of gastric cancer patients are distinct from those of patients without cancer, but the microbial alterations that occur along the process of gastric carcinogenesis, and the mechanisms through which microorganisms influence cancer progression still need to be clarified. Except for Epstein-Barr virus, the potential significance of the virome and of the mycobiome in gastric cancer have received less attention. This chapter updates the current knowledge regarding the gastric microbiome, including bacteria, viruses, and fungi, within the context of H. pylori-mediated carcinogenesis. It also reviews the possible roles of the local gastric microbiota, as well as the microbial communities of the oral and gut ecosystems, as biomarkers for gastric cancer detection. Finally, it discusses future perspectives and acknowledges limitations in the area of microbiome research in the gastric cancer setting, to which further research efforts should be directed. These will be fundamental not only to increase our current understanding of host-microbial interactions but also to facilitate translation of the findings into innovative preventive, diagnostic, and therapeutic strategies to decrease the global burden of gastric cancer.

The Tissue-Associated Microbiota in Colorectal Cancer: A Systematic Review.

The intestinal microbiome is associated with colorectal cancer. Although the mucosal microbiota better represents an individual's local microbiome, studies on the colorectal cancer microbiota mainly reflect knowledge obtained from fecal samples. This systematic review aimed to summarize the current evidence on the relationship between the mucosal-associated bacterial microbiota and colorectal cancer. Searches were conducted in PubMed and Web of Science databases for publications comparing the mucosal microbiome of colorectal cancer patients with that of healthy controls, or with that of non-cancerous mucosal tissues. The primary outcomes were differences in microbial diversity and taxonomy. The Newcastle-Ottawa Scale was used to assess the quality of the included studies. Of the 5080 studies identified, 39 were eligible and included in the systematic review. No consistent results were identified for the α- and ß-diversity, due to high heterogeneity in reporting and to differences in metrics and statistical approaches, limiting study comparability. Qualitative synthesis of microbial taxonomy identified 12 taxa with strong positive and 18 taxa with strong negative associations with colorectal cancer. Fusobacterium, Campylobacter, Parvimonas, Peptostreptococcus, Streptococcus, and Granulicatella were defined as enriched in colorectal cancer. Despite the methodological limitations of the studies, consistent evidence on bacterial taxa associated with colorectal cancer was identified. Prospective studies in large and well-characterized patient populations will be crucial to validate these findings.

Modulation of the resistance to norfloxacin in Staphylococcus aureus by Bauhinia forficata link.

Microdilution assays were performed in order to evaluate the antimicrobial activity of the ethanoic extract from the leaves of Bauhinia forficate (EEBF) against different microorganisms. The extract did not present inner antimicrobial activities against the tested strains. However, EEBF was able to modulate the norfloxacin-resistance against Staphylococcus aureus SA1199-B that overproduce the NorA efflux pump, once sub-inhibitory concentrations of EEBF reduced the minimal inhibitory concentratio of the norfloxacin in 87.5%. This modulatory effect was also found when the antibiotic was replaced by ethidium bromide, suggesting that EEBF acts probably by inhibition of NorA, allowing the antibiotic accumulation intracellularly, and making the line more sensitive. These results point out the EEBF potential as a source of NorA inhibitors that could be used in combination with norfloxacin for treatment of infections caused by multidrug-resistant S. aureus.

Development of an Antisense Oligonucleotide-Mediated Exon Skipping Therapeutic Strategy for Mucolipidosis II: Validation at RNA Level.

Lysosomal storage disorders (LSDs) are a group of rare inherited metabolic diseases caused by the malfunction of the lysosomal system, which results in the accumulation of undergraded substrates inside the lysosomes and leads to severe and progressive pathology. Despite there currently being a broad understanding of the molecular defects behind LSDs, curative therapies have been approved for only few of these diseases, whereas existing treatments are still mostly symptomatic with several limitations. Mucolipidosis type II alpha/beta (ML II) is one of most severe LSDs, which is caused by the total deficiency of the GlcNAc-1-phosphotransferase, a key enzyme for the formation of specific targeting signals on lysosomal hydrolases to lysosomes. GlcNAc-1-phosphotransferase is a multimeric enzyme complex encoded by two genes: GNPTAB and GNPTG. One of the most frequent ML II causal mutation is a dinucleotide deletion on exon 19 of GNPTAB (c.3503_3504del) that leads to the generation of a truncated protein, loss of GlcNAc-1-phosphotransferase activity, and missorting of multiple lysosomal enzymes. Presently, there is no therapy available for ML II. In this study, we explored the possibility of an innovative therapeutic strategy for ML II based on the use of antisense oligonucleotides (AOs) capable to induce the skipping of GNPTAB exon 19 harboring the most common disease-causing mutation, c.3503_3504del. The approach confirmed the ability of specific AOs for RNA splicing modulation, thus paving the way for future studies on the therapeutic potential of this strategy.

Estudo exploratório do relacionamento conjugal em casais com um dos cônjuges brasileiro / Exploratory study of conjugal relationship in couples with one brazilian member

Razões históricas, culturais e socioeconômicas determinaram a importância de certo nível de igualdade entre cônjuges, caracterizando um processo de homogamia. Tal homogamia garantiria compatibilidade de interesses e de características pessoais, familiares, culturais, de classe e raciais. Casais com um cônjuge brasileiro podem informar sobre estabelecimento e consolidação de relações conjugais em condições de grande valor heurístico, que não são, em princípio, de homogamia. Investigamos condições de estabelecimento e consolidação de relacionamento em casais com distintas perspectivas culturais em jogo. Entrevistamos 12 brasileiras e 3 brasileiros casados com parceiros nascidos e criados em 10 países diferentes e que, à época do casamento, tinham idade entre 20 e 57 anos. Os dados foram organizados e analisados a partir de análise de conteúdo. Diferenças culturais não representaram barreiras expressivas ao entendimento conjugal, ao relacionamento com as famílias de origem e à criação dos filhos. A utilização cotidiana do idioma português predominou com o desenvolvimento da vida conjugal. A maior parte dos entrevistados conheceu seus cônjuges no Brasil (11 casos) e todos tinham vida profissional ou de estudo à época. A vida profissional dos homens foi expressivamente menos afetada do que a das mulheres. Os dados revelaram que casamento com cônjuge estrangeiro, dependendo do equilíbrio de características de formação, experiência e maturidade existencial, pode não representar situação de grande heterogamia

Estudo exploratório do relacionamento conjugal em casais com um dos cônjuges brasileiro / Exploratory study of conjugal relationship in couples with one brazilian member

Razões históricas, culturais e socioeconômicas determinaram a importância de certo nível de igualdade entre cônjuges, caracterizando um processo de homogamia. Tal homogamia garantiria compatibilidade de interesses e de características pessoais, familiares, culturais, de classe e raciais. Casais com um cônjuge brasileiro podem informar sobre estabelecimento e consolidação de relações conjugais em condições de grande valor heurístico, que não são, em princípio, de homogamia. Investigamos condições de estabelecimento e consolidação de relacionamento em casais com distintas perspectivas culturais em jogo. Entrevistamos 12 brasileiras e 3 brasileiros casados com parceiros nascidos e criados em 10 países diferentes e que, à época do casamento, tinham idade entre 20 e 57 anos. Os dados foram organizados e analisados a partir de análise de conteúdo. Diferenças culturais não representaram barreiras expressivas ao entendimento conjugal, ao relacionamento com as famílias de origem e à criação dos filhos. A utilização cotidiana do idioma português predominou com o desenvolvimento da vida conjugal. A maior parte dos entrevistados conheceu seus cônjuges no Brasil (11 casos) e todos tinham vida profissional ou de estudo à época. A vida profissional dos homens foi expressivamente menos afetada do que a das mulheres. Os dados revelaram que casamento com cônjuge estrangeiro, dependendo do equilíbrio de características de formação, experiência e maturidade existencial, pode não representar situação de grande heterogamia (AU)