ALCAM/CD166 is involved in the binding and uptake of cancer-derived extracellular vesicles

Colorectal cancer (CRC) and ovarian cancer (OvC) patients frequently develop peritoneal metastasis, a condition associated with a very poor prognosis. In these cancers, tumor-derived extracellular vesicles (EVs) cause immunosuppression, facilitate the direct attachment and invasion of cancer cells through the mesothelium, induce the conversion of peritoneal mesothelial cells (PMCs) into cancer-associated fibroblasts (CAFs) and transfer a more aggressive phenotype amongst cancer cells. Although the promoting role of EVs in CRC and OvC peritoneal metastasis is well established, the specific molecules that mediate the interactions between tumor-derived EVs and immune and non-immune target cells remain elusive. Here, we employed the SKOV-3 (ovarian adenocarcinoma) and Colo-320 (colorectal adenocarcinoma) human cell lines as model systems to study the interactions and uptake of EVs produced by ovarian carcinoma and colorectal carcinoma cells, respectively. We established that the adhesion molecule ALCAM/CD166 is involved in the interaction of cancerderived EVs with recipient cancer cells (a process termed “EV binding” or “EV docking”) and in their subsequent uptake by these cells. The identification of ALCAM/CD166 as a molecule mediating the docking and uptake of CRC and OvC-derived EVs may be potentially exploited to block the peritoneal metastasis cascade promoted by EVs in CRC and OvC patient

ALCAM/CD166 Is Involved in the Binding and Uptake of Cancer-Derived Extracellular Vesicles

Colorectal cancer (CRC) and ovarian cancer (OvC) patients frequently develop peritoneal metastasis, a condition associated with a very poor prognosis. In these cancers, tumor-derived extracellular vesicles (EVs) cause immunosuppression, facilitate the direct attachment and invasion of cancer cells through the mesothelium, induce the conversion of peritoneal mesothelial cells (PMCs) into cancer-associated fibroblasts (CAFs) and transfer a more aggressive phenotype amongst cancer cells. Although the promoting role of EVs in CRC and OvC peritoneal metastasis is well established, the specific molecules that mediate the interactions between tumor-derived EVs and immune and non-immune target cells remain elusive. Here, we employed the SKOV-3 (ovarian adenocarcinoma) and Colo-320 (colorectal adenocarcinoma) human cell lines as model systems to study the interactions and uptake of EVs produced by ovarian carcinoma and colorectal carcinoma cells, respectively. We established that the adhesion molecule ALCAM/CD166 is involved in the interaction of cancer-derived EVs with recipient cancer cells (a process termed “EV binding” or “EV docking”) and in their subsequent uptake by these cells. The identification of ALCAM/CD166 as a molecule mediating the docking and uptake of CRC and OvC-derived EVs may be potentially exploited to block the peritoneal metastasis cascade promoted by EVs in CRC and OvC patients

Endocytosis as a biological response in receptor pharmacology: evaluation by fluorescence microscopy

The activation of G-protein coupled receptors by agonist compounds results in diverse biological responses in cells, such as the endocytosis process consisting in the translocation of receptors from the plasma membrane to the cytoplasm within internalizing vesicles or endosomes. In order to functionally evaluate endocytosis events resulted from pharmacological responses, we have developed an image analysis method -the Q-Endosomes algorithm- that specifically discriminates the fluorescent signal originated at endosomes from that one observed at the plasma membrane in images obtained from living cells by fluorescence microscopy. Mu opioid (MOP) receptor tagged at the carboxy-terminus with yellow fluorescent protein (YFP) and permanently expressed in HEK293 cells was used as experimental model to validate this methodology. Time-course experiments performed with several agonists resulted in different sigmoid curves depending on the drug used to initiate MOP receptor endocytosis. Thus, endocytosis resulting from the simultaneous activation of co-expressed MOP and serotonin 5-HT2C receptors by morphine plus serotonin was significantly different, in kinetics as well as in maximal response parameters, from the one caused by DAMGO, sufentanyl or methadone. Therefore, this analytical tool permits the pharmacological characterization of receptor endocytosis in living cells with functional and temporal resolution

Communicating risk during early phases of COVID-19: Comparing governing structures for emergency risk communication across four contexts

BackgroundEmergency risk communication (ERC) is key to achieving compliance with public health measures during pandemics. Yet, the factors that facilitated ERC during COVID-19 have not been analyzed. We compare ERC in the early stages of the pandemic across four socio-economic settings to identify how risk communication can be improved in public health emergencies (PHE).MethodsTo map and assess the content, process, actors, and context of ERC in Germany, Guinea, Nigeria, and Singapore, we performed a qualitative document review, and thematically analyzed semi-structured key informant interviews with 155 stakeholders involved in ERC at national and sub-national levels. We applied Walt and Gilson's health policy triangle as a framework to structure the results.ResultsWe identified distinct ERC strategies in each of the four countries. Various actors, including governmental leads, experts, and organizations with close contact to the public, collaborated closely to implement ERC strategies. Early integration of ERC into preparedness and response plans, lessons from previous experiences, existing structures and networks, and clear leadership were identified as crucial for ensuring message clarity, consistency, relevance, and an efficient use of resources. Areas of improvement primarily included two-way communication, community engagement, and monitoring and evaluation. Countries with recurrent experiences of pandemics appeared to be more prepared and equipped to implement ERC strategies.ConclusionWe found that considerable potential exists for countries to improve communication during public health emergencies, particularly in the areas of bilateral communication and community engagement as well as monitoring and evaluation. Building adaptive structures and maintaining long-term relationships with at-risk communities reportedly facilitated suitable communication. The findings suggest considerable potential and transferable learning opportunities exist between countries in the global north and countries in the global south with experience of managing outbreaks

Paisagem

Neste número temático da revista Estúdio lançou-se o desafio aos criadores e artistas para debaterem e estudarem a obra de seus companheiros de profissão, outros artistas, dentro do tema da paisagem.Poderemos, a posteriori, agrupar os 39 artigos, aqui aprovados e apresentados, segundo quatro eixos temáticos: a. Testemunho da paisagem; b. Perda da paisagem; c. Paisagens urbanas; d. Sustentabilidade. No primeiro núcleo, testemunho da paisagem, consideramos os artigos que refletem sobre artistas cuja obra integra uma componente contemplativa, onde se sente a busca de um sentido profundo. No segundo núcleo, perda da paisagem, poderemos agrupar os artigos que se debruçam sobre formas de resgate de algo que se sente estar perdido. Reflete-se sobre os vestígios de um mundo antigo, sem quebras, sem separações entre o homem e a natureza, ou sobre a nostalgia da sua recuperação através de uma redenção introspetiva. No terceiro núcleo, paisagens urbanas, encontramos artigos que meditam sobre a textura ambiental urbana e sobre os meios de simulação inerentes aos recursos cenográficos presentes nos espaços públicos e partilhados por um elo social: os espaços codificados. No quarto núcleo acompanhamos a tendência mais ou menos ativista, onde o artista carrega o peso do perigo, a ameaça sobre os sistemas vivos, e receia o fim das paisagens. A sustentabilidade exige agilidade e alterações nos estilos de vida, exige uma economia reinventada. Agruparam-se assim os artigos seguindo uma teia de afinidades, sendo decerto uma organização segundo critérios de oportunidade temática: encontrar texturas globais no tecido do discurso sobre arte, nos textos dos artistasinfo:eu-repo/semantics/publishedVersio

AVASUS’ Contributions to Promoting Lifelong Learning in Health: Toward Achieving the SDGs and Strengthening Global Health Security

The Virtual Learning Environment of the Brazilian Health System (AVASUS) was developed by the Laboratory for Technological Innovation in Health (LAIS) and the Secretariat of Distance Education (SEDIS) at the Federal University of Rio Grande do Norte (UFRN) in partnership with Brazil’s Ministry of Health (MoH). AVASUS provides open educational resources in the health field and has emerged as the third largest platform for massive health education globally, with more than one million students. Among the various learning pathways AVASUS offers, some specifically focus on meeting the educational needs to address public health emergencies and overlooked health contexts. The main argument in this study is that technology-mediated lifelong learning in health is an effective strategy for achieving the Sustainable Development Goals (SDGs) of the 2030 Agenda. This chapter analyzes the pathways related to COVID-19, syphilis, and prison health, focusing on the contributions towards achieving SDGs 3, 4, 5, 10, 11, 16, and 17 and fulfilling the Global Health Security Agenda. Our analysis revealed two key findings. Lifelong learning in health (i) prompts decision-making on public health policies and (ii) contributes towards implementing the SDGs. Ultimately, AVASUS should be recognized as a tool to improve health services and support policy-making

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Umbilical cord blood coagulability, acidosis and intracranial hemorrhage

Peer Reviewe

Generation of an inducible double-stable cell line expressing MOP-YFP and c-myc-5-HT_2C-Cerulean receptors.

<p>Images obtained by confocal microscopy from living Flp-In HEK293 cells expressing permanently MOP-YFP receptors and c-myc-5-HT_2C-Cerulean receptors in an inducible manner. The right column corresponds to the images resulting after exciting the cells with the YFP light settings whereas in the left column are the same microscopy field illuminated for CFP visualization. When indicated, +DOX corresponds to treatment with doxycycline (0.01 μg/ml) for 24 hours prior to microscope observation.</p

Effect of different doses of serotonin (5-HT) on the facilitation of the endocytosis of MOP-YFP receptors by morphine.

<p><b>A.</b> Data graph display representative results from time-course MOP-YFP receptor endocytosis experiments conducted by co-treatment with morphine at 10 μM plus 5-HT at different concentrations (see symbol legends). <b>B.</b> Dose-response curve (continuous line) obtained after non-linear analysis of the maximal effect (number of vesicles per cell) generated by morphine (10 μM) plus different concentrations of 5-HT. Each point represents the mean ± SEM of three independent experiments. Dotted line display the characteristic bell shaped profile observed when connecting these points in an increasing dose-dependent manner.</p