High-Throughput Drug Screening Revealed That Ciclopirox Olamine Can Engender Gastric Cancer Stem-like Cells.

Cancer stem cells (CSCs) are relevant therapeutic targets for cancer treatment. Still, the molecular circuits behind CSC characteristics are not fully understood. The low number of CSCs can sometimes be an obstacle to carrying out assays that explore their properties. Thus, increasing CSC numbers via small molecule-mediated cellular reprogramming appears to be a valid alternative tool. Using the SORE6-GFP reporter system embedded in gastric non-CSCs (SORE6-), we performed a high-throughput image-based drug screen with 1200 small molecules to identify compounds capable of converting SORE6- to SORE6+ (CSCs). Here, we report that the antifungal agent ciclopirox olamine (CPX), a potential candidate for drug repurposing in cancer treatment, is able to reprogram gastric non-CSCs into cancer stem-like cells via activation of SOX2 expression and increased expression of C-MYC, HIF-1α, KLF4, and HMGA1. This reprogramming depends on the CPX concentration and treatment duration. CPX can also induce cellular senescence and the metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis. We also disclose that the mechanism underlying the cellular reprogramming is similar to that of cobalt chloride (CoCl2), a hypoxia-mimetic agent.

Nutshells as Efficient Biosorbents to Remove Cadmium, Lead, and Mercury from Contaminated Solutions.

The release of potentially toxic elements into the environment, and their effects on aquatic ecosystems still present a real threat. To avoid such contamination, the use of biological sorbents as an alternative to conventional and expensive water remediation techniques has been proposed. The present study evaluated the potential of 0.5 g L-1 of peanut, hazelnut, pistachio, walnut, and almond shells to remove the requisite concentrations of cadmium (Cd), lead (Pb), and mercury (Hg) from contaminated water. Hazelnut shells were identified as the sorbent with the highest potential and were evaluated in mono- and multi-contaminated mineral water. The influence of sorbent-intrinsic and solution-intrinsic characteristics were assessed. Differences among sorbents were attributed to varying percentages of their main components: cellulose, hemicellulose, and lignin. Matrix complexity increase caused a decrease in Cd removal, presumably due to the diminution in electrostatic interaction, and complexation with anions such as Cl-. When simultaneously present in the solution, contaminants competed, with Pb showing higher affinity to the sorbent than Hg. High efficiencies (>90%) obtained for hazelnut shells for all elements in ultrapure water and for Pb and Hg in mineral water) reveals the high potential of this low-cost and abundant waste for use in the remediation of contaminated waters (circular economy).

HMGA1 Has Predictive Value in Response to Chemotherapy in Gastric Cancer.

Gastric cancer is a serious health problem worldwide. Although its incidence is decreasing, the five-year survival rate remains low. Thus, it is essential to identify new biomarkers that could promote better diagnosis and treatment of patients with gastric cancer. High-mobility group AT-hook 1 (HMGA1) is a non-histone, chromatin-binding protein that has been found overexpressed in several tumor types. It has been correlated with invasion, metastasis, and drug resistance, leading to worse patient survival. The aim of this work was to evaluate the clinical value of HMGA1 in gastric cancer. HMGA1 expression was analyzed by immunohistochemistry in a single hospital series (n = 323) of gastric adenocarcinoma cases (stages I to IV) with clinicopathological and treatment data. In this series, HMGA1 expression showed no significant relevance as a prognostic biomarker. Nevertheless, a significantly better overall survival was observed in cases with high levels of HMGA1 when they were treated with chemotherapy, compared to the nontreated ones, implying that they can benefit more from treatment than patients with low expression of HMGA1. We thereby show for the first time that HMGA1 expression has a substantial value as a biomarker of response to chemotherapy in gastric cancer.

The Relevance of Transcription Factors in Gastric and Colorectal Cancer Stem Cells Identification and Eradication.

Gastric and colorectal cancers have a high incidence and mortality worldwide. The presence of cancer stem cells (CSCs) within the tumor mass has been indicated as the main reason for tumor relapse, metastasis and therapy resistance, leading to poor overall survival. Thus, the elimination of CSCs became a crucial goal for cancer treatment. The identification of these cells has been performed by using cell-surface markers, a reliable approach, however it lacks specificity and usually differs among tumor type and in some cases even within the same type. In theory, the ideal CSC markers are those that are required to maintain their stemness features. The knowledge that CSCs exhibit characteristics comparable to normal stem cells that could be associated with the expression of similar transcription factors (TFs) including SOX2, OCT4, NANOG, KLF4 and c-Myc, and signaling pathways such as the Wnt/ß-catenin, Hedgehog (Hh), Notch and PI3K/AKT/mTOR directed the attention to the use of these similarities to identify and target CSCs in different tumor types. Several studies have demonstrated that the abnormal expression of some TFs and the dysregulation of signaling pathways are associated with tumorigenesis and CSC phenotype. The disclosure of common and appropriate biomarkers for CSCs will provide an incredible tool for cancer prognosis and treatment. Therefore, this review aims to gather the new insights in gastric and colorectal CSC identification specially by using TFs as biomarkers and divulge promising drugs that have been found and tested for targeting these cells.

Evidence for contrasting accumulation pattern of cadmium in relation to other elements in Senilia senilis and Tagelus adansoni from the Bijagós archipelago, Guinea-Bissau.

Shellfish harvesting in intertidal areas is a widespread and economically important activity in many countries across West Africa. However, in some areas, there is virtually no information concerning the levels of contaminants (and other elements related to nutritional aspects) in the harvested species. We collected sediments and several individuals of the West African bloody cockle Senilia senilis and of the razor clam Tagelus adansoni during the dry season of 2015 nearby three islands in the Bijagós archipelago, Guinea-Bissau. Aluminium, Ca, Fe, Mg, As, Cd, Co, Cr, Cu, Mn, Ni, Pb and Zn were determined in sediments and whole soft tissues of the two bivalves. Sediments showed uniformly low trace element concentrations, pointing to an ecosystem with low levels of trace element contamination. T. adansoni presented higher concentrations of most elements than S. senilis, with the exception of Cd that showed up to 40 times higher values in S. senilis than in T. adansoni from the same sites. Furthermore, Cd concentrations (25±8.7 mg kg-1, dw) in S. senilis are clearly above the maximum level established for human consumption. Future studies should clarify whether biological factors are the major responsible for this unusual situation.

Considerações sobre os movimentos de medicalização da vida / Considerations on life's medicalization movements / Consideraciones sobre los movimientos de medicalización de la vida

A ideia de que problemas cotidianos são diagnosticáveis e tratáveis pela medicina é antiga e ao mesmo tempo comum na atualidade, na qual habituou-se entender e explicar a vida psíquica e as condutas éticas pelo conhecimento da materialidade corporal. Este artigo realiza uma análise sobre a relação entre o saber biomédico e pedagógico na construção da concepção de infância normal/anormal. Nas duas últimas décadas, o investimento em pesquisas que investigam o funcionamento cerebral tem ampliado significativamente o conhecimento científico das interações entre o físico e o psicológico e sustenta fortemente a cultura somática. Nesse processo, diagnósticos psiquiátricos se tornaram dispositivos importantes na explicação e intervenção dos processos de escolarização considerados problemáticos. No percurso teórico investigado, destaca-se como a combinação entre as ciências biomédicas e a educação marcou e tem marcado as práticas de intervenção sobre os problemas enfrentados pelas crianças ao ingressarem na escola.

The idea that everyday problems are diagnosable and treatable by medicine is ancient as well as common today, when we are used to understanding and explaining the psyche and ethical conduct by knowing the materiality of the body. In the last two decades, investment in research investigating brain functioning has significantly expanded scientific knowledge of physiological and psychological interactions, which strongly support somatic culture. Thus, psychiatric diagnoses have become important tools in the explanation and intervention of schooling procedures considered "problematic". The combination of biomedical sciences and education has had an impact on intervention practices regarding the problems faced by children when they enter school. We are going to take a diachronic look at the relationship between biomedical knowledge and pedagogy that created the concept of normal/abnormal childhood.

La idea de que problemas cotidianos son diagnosticables y tratables por la medicina é antigua y al mismo tiempo común en la actualidad, donde se habituó a entender y explicar la vida psíquica y de las conductas éticas por el conocimiento de la materialidad corporal. Este artículo realiza un análisis sobre la relación entre el saber biomédico y pedagógico en la construcción de la concepción de infancia normal/anormal. En las dos últimas décadas, el patrocinio de investigaciones que se interesan por el funcionamiento cerebral, ha ampliado significativamente el conocimiento científico de las interacciones entre lo físico y lo psicológico y sustenta fuertemente la cultura somática. En este proceso, diagnósticos psiquiátricos se convirtieron en dispositivos importantes para la explicación e intervención de los procesos de escolarización considerados problemáticos. En el recorrido teórico investigado, se destaca como la combinación entre las ciencias biomédicas y la educación ha marcado las prácticas de intervención sobre los problemas enfrentados por los niños al ingresar a las instituciones educativas.

Stem cells in endometrium and their role in the pathogenesis of endometriosis.

The human endometrium is a dynamic tissue that undergoes cycles of growth and regression with each menstrual cycle. Adult progenitor stem cells are likely responsible for this remarkable regenerative capacity; these same progenitor stem cells may also have an enhanced capacity to generate endometriosis if shed in a retrograde fashion. The progenitor stem cells reside in the uterus; however, less-committed mesenchymal stem cells may also travel from other tissues such as bone marrow to repopulate the progenitor population. Mesenchymal stem cells are also involved in the pathogenesis of endometriosis and may be the principle source of endometriosis outside of the peritoneal cavity when they differentiate into endometriosis in ectopic locations. Finally, besides progenitor stem cells, recent publications have identified multipotent stem cells in the endometrium. These multipotent stem cells are a readily available source of cells that are useful in tissue engineering and regenerative medicine. Endometrial stem cells have been used to generate chondrocytes, myocytes, neurons, and adiposites in vitro as well as to replace dopaminergic neurons in a murine model of Parkinson's disease.

Estudo do desempenho da dopplervelocimetria e dos métodos de avaliação das atividades biofísicas fetais na predição das condições pós-natais adversas / Doppler velocimetry and fetal well-being assess, exams performance's study for adverse neonatal outcomes

Este estudo retrospectivo e transversal teve como objetivo verificar o desempenho dos exames antenatais, para a predição de resultados pós-natais adversos. Selecionaram-se 1387 pacientes com alto risco gestacional, no Setor de Avaliação da Vitalidade Fetal, da Clínica Obstétrica do Hospital das Clínicas da FMUSP. O desempenho de todos os exames foi testado, para a predição dos resultados pós-natais adversos, por meio do cálculo da sensibilidade, especificidade, VPP e VPN / The aim of this retrospective study was to assess the role prenatal exams to predict neonatal adverse outcomes. The sample was divided accoding to maternal and gestational complications, as placental insufficiency sthiology. Furthermore, the predictive values of the exams were analyzed in relation to postnatal adverse outcomes. The sample was constituted by 1,387 high-risk pregnancies assisted in the Obstetrics Department - Fetal Well-being Assessment Section of the Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo - Brazil. The performance of all prenatal enrolled exams were evaluated in order to predict the adverse outcomes, using sensitivity, specificity, PPV and NPV estimations...