Infective Endocarditis: A Focus on Oral Microbiota

Infective endocarditis (IE) is an inflammatory disease usually caused by bacteria entering the bloodstream and settling in the heart lining valves or blood vessels. Despite modern antimicrobial and surgical treatments, IE continues to cause substantial morbidity and mortality. Thus, primary prevention and enhanced diagnosis remain the most important strategies to fight this disease. In this regard, it is worth noting that for over 50 years, oral microbiota has been considered one of the significant risk factors for IE. Indeed, among the disparate recommendations from the American heart association and the European Society of Cardiology, there are good oral hygiene and prophylaxis for high-risk patients undergoing dental procedures. Thus, significant interest has grown in the role of oral microbiota and it continues to be a subject of research interest, especially if we consider that antimicrobial treatments can generate drug-resistant mutant bacteria, becoming a severe social problem. This review will describe the current knowledge about the relationship between oral microbiota, dental procedures, and IE. Further, it will discuss current methods used to prevent IE cases that originate from oral pathogens and how these should be focused on improving oral hygiene, which remains the significant persuasible way to prevent bacteremia and systemic disorders

Regulation and function of the atypical cadherin FAT1 in hepatocellular carcinoma

Giant cadherin FAT1 is increased in HCC and is a protumorigenic factors in HCC cell

Educomunicação e suas áreas de intervenção: Novos paradigmas para o diálogo intercultural

oai:omp.abpeducom.org.br:publicationFormat/1O material aqui divulgado representa, em essência, a contribuição do VII Encontro Brasileiro de Educomunicação ao V Global MIL Week, da UNESCO, ocorrido na ECA/USP, entre 3 e 5 de novembro de 2016. Estamos diante de um conjunto de 104 papers executivos, com uma média de entre 7 e 10 páginas, cada um. Com este rico e abundante material, chegamos ao sétimo e-book publicado pela ABPEducom, em seus seis primeiros anos de existência. A especificidade desta obra é a de trazer as “Áreas de Intervenção” do campo da Educomunicação, colocando-as a serviço de uma meta essencial ao agir educomunicativo: o diálogo intercultural, trabalhado na linha do tema geral do evento internacional: Media and Information Literacy: New Paradigms for Intercultural Dialogue

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

FAT1 expression and function in chronic liver disease and hepatocellular carcinoma

FAT1 is a member of the atypical cadherin FAT subfamily. The first identified member of this family was Drosophila Fat which has been regarded as a tumor suppressor because of its implication in tissue growth. In vertebrates FAT subfamily consists of 4 members, FAT1, -2, -3 and FAT-J (or FAT4). Only FAT1 has so far been studied more intensively. FAT1 is expressed in a wide range of tissues and a homozygous knockout for FAT1 in mice was perinatal lethal. In vitro studies indicate that it is involved in cell polarity and migration. Cancer research revealed deregulated FAT1 expression. In some tumors as breast cancer FAT1 is over-expressed while FAT1 expression is reduced or deleted in others as astrocytic tumors or cholangiocarcinoma. In the present work, we first analyzed the role of FAT1 in chronic liver disease. We found FAT1 upregulation in a murine model of non-alcoholic steatohepatitis (NASH) and could confirm this result in human tissue from NASH patients. Moreover, we detected induced FAT1 expression in further murine models of chronic liver injury. Thus, bile duct ligation (BDL) as well as hepatotoxic thioacetamide (TAA) administration induced hepatic upregulation of FAT1 expression. Furthermore, FAT1 expression was significantly heightened in cirrhotic human liver tissue. Activated hepatic stellate cells (HSC) were identified as the main cellular source of FAT1 in chronic liver disease. Suppression of FAT1 by siRNA inhibited NFκB activation and thereto proinflammatory gene expression, and reduced apoptosis resistance in activated HSC. Next, we investigated FAT1 expression and function in hepatocellular carcinoma (HCC). FAT1 expression was significantly upregulated in HCC cell lines as well as in HCC tumor tissue compared to primary human hepatocytes (PHH) and non-tumorous liver tissue. In human HCC tissues strong FAT1 expression correlated with tumor stage and proliferation rate. Stable suppression of FAT1 by shRNA transfection reduced proliferation as well as migratory potential of HCC cells. Moreover, cells with suppressed FAT1 expression demonstrated higher susceptibility towards apoptosis, induced by serum starvation. To evaluate the role of FAT1 in HCC in vivo we injected stable FAT1 suppressed cells into nude mice. We observed delayed tumor onset and more apoptotic cells in tumors derived from FAT1 suppressed cell clones. Finally, we searched for mechanisms responsible for FAT1 upregulation in HCC. We found that hepatocyte growth factor (HGF), a factor secreted by activated HSCs, induced FAT1 expression in vitro. FAT1 expression was further increased in HCC cells under hypoxia, and this induction was strongly repressed by inhibition of hypoxia inducible factor 1 alpha (HIF1α). Hypoxia caused significantly reduced levels of the methyl group donor S-adenosylmethionine (SAM), and SAM supplementation inhibited the hypoxia induced FAT1 expression in HCC cells. Conversely, demethylating agents induced FAT1 expression in HCC cells, and expression analysis in 24 human HCC tissues showed a significant correlation between FAT1 and MAT2A, which is known to critically affect SAM levels in HCC. In conclusion, increased FAT1 expression in chronic liver disease and HCC functionally promotes the course of disease and thereto may be a new therapeutic target for the prevention and treatment of hepatic fibrosis in chronic liver disease and hepatocellular carcinoma

Increased expression of zinc finger protein 267 in non-alcoholic fatty liver disease.

Hepatocellular lipid accumulation is a hallmark of non-alcoholicfatty liver disease (NAFLD), which encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and ultimately cirrhosis. Zinc finger protein 267 (ZNF267) belongs to the family of Kruppel-like transcription factors, which regulate diverse biological processes that include development, proliferation, and differentiation. We have previously demonstrated that ZNF267 expression is up-regulated in liver cirrhosis and is further increased in hepatocellular carcinoma (HCC). Here, we analyzed the expression of ZNF267 in tissue specimens of NAFLD patients and found a significant up-regulation compared to normal liver tissue. Noteworthy, ZNF267 mRNA was already significantly increased in steatotic liver tissue without inflammation. In line with this, incubation of primary human hepatocytes with palmitic acid induced a dose-dependent lipid accumulation and corresponding dose-dependent ZNF267 induction in vitro. Furthermore, hepatocellular lipid accumulation induced formation of reactive oxygen species (ROS), and also chemically induced ROS formation increased ZNF267 mRNA expression. In summary with previous findings, which revealed ZNF267 as pro-fibrogenic and pro-cancerogenic factor in chronic liver disease, the present study further suggests ZNF267 as promising therapeutic target particularly for NAFLD patients. In addition, it further indicates that hepatic steatosis per se has pathophysiological relevance and should not be considered as benign

Cisplatin, glutathione and the third wheel: a copper-(1,10-phenanthroline) complex modulates cisplatin–GSH interactions from antagonism to synergism in cancer cells resistant to cisplatin

A new drug cocktail is proposed to overcome the cisplatin-resistance due to the presence of glutathione. A2780 cisplatin-resistant cells, treated with the drug cocktail, showed early apoptosis