The extracellular small leucine-rich proteoglycan biglycan is a key player in gastric cancer aggressiveness

Biglycan (BGN gene), an extracellular proteoglycan, has been described to be associated with cancer aggressiveness. The purpose of this study was to clarify the clinical value of biglycan as a biomarker in multiple independent GC cohorts and determine the in vitro and in vivo role of biglycan in GC malignant features. We found that BGN is commonly over-expressed in all analyzed cohorts, being associated with disease relapse and poor prognosis in patients with advanced stages of disease. In vitro and in vivo experiments demonstrated that biglycan knock-out GC cells display major phenotypic changes with a lower cell survival, migration, and angiogenic potential when compared with biglycan expressing cells. Biglycan KO GC cells present increased levels of PARP1 and caspase-3 cleavage and a decreased expression of mesenchymal markers. Importantly, biglycan deficient GC cells that were supplemented with exogenous biglycan were able to restore biological features, such as survival, clonogenic and migratory capacities. Our in vitro and in vivo findings were validated in human GC samples, where BGN expression was associated with several oncogenic gene signatures that were associated with apoptosis, cell migration, invasion, and angiogenesis. This study provided new insights on biglycan role in GC that should be taken in consideration as a key cellular regulator with major impact in tumor progression and patients’ clinical outcome.This work was funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE (POCI-01-0145-FEDER-016585; POCI-01-0145-FEDER-029780; POCI-01-0145-FEDER-007274; POCI-01-0145-FEDER-029780) and National Funds through the Foundation for Science and Technology (FCT), under the projects: PTDC/BBB-EBI/0567/2014 (to C.A.R.), PTDC/MED-QUI/29780/2017 (to CG), and UID/BIM/04293 supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). F.P. was funded by FCT cofinanced by Fundo Social Europeu-FSE with a grant with reference: SFRH/BPD/115730/2016

The chick chorioallantoic membrane model: A new in vivo tool to evaluate breast cancer stem cell activity

The high plasticity of cancer stem-like cells (CSCs) allows them to differentiate and proliferate, specifically when xenotransplanted subcutaneously into immunocompromised mice. CSCs are highly tumorigenic, even when inoculated in small numbers. Thus, in vivo limiting dilution assays (LDA) in mice are the current gold standard method to evaluate CSC enrichment and activity. The chick embryo chorioallantoic membrane (CAM) is a low cost, naturally immuneincompetent and reproducible model widely used to evaluate the spontaneous growth of human tumor cells. Here, we established a CAM-LDA assay able to rapidly reproduce tumor specificities— in particular, the ability of the small population of CSCs to form tumors. We used a panel of organotropic metastatic breast cancer cells, which show an enrichment in a stem cell gene signature, enhanced CD44+/CD24-/low cell surface expression and increased mammosphere-forming efficiency (MFE). The size of CAM-xenografted tumors correlate with the number of inoculated cancer cells, following mice xenograft growth pattern. CAM and mice tumors are histologically comparable, displaying both breast CSC markers CD44 and CD49f. Therefore, we propose a new tool for studying CSC prevalence and function—the chick CAM-LDA—a model with easy handling, accessibility, rapid growth and the absence of ethical and regulatory constraints.This work was funded by FEDER—Fundo Europeu de Desenvolvimento Regional— funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior under the projects PestC/SAU/LA0003/2013, NORTE-01-0145-FEDER-000029, SAICTPAC/0022/2015 and FCT/02/SAICT/2017/030625. FCT funded the research grant of RC (SFRH/BD/135831/2018). IPATIMUP integrated the i3S Research Unit, which was partially supported by FCT in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145FEDER-007274)

Single-cell transcriptional profiling reveals cellular diversity and intercommunication in the mouse heart

Characterization of the cardiac cellulome, the network of cells that form the heart, is essential for understanding cardiac development and normal organ function and for formulating precise therapeutic strategies to combat heart disease. Recent studies have reshaped our understanding of cardiac cellular composition and highlighted important functional roles for non-myocyte cell types. In this study, we characterized single-cell transcriptional profiles of the murine non-myocyte cardiac cellular landscape using single-cell RNA sequencing (scRNA-seq). Detailed molecular analyses revealed the diversity of the cardiac cellulome and facilitated the development of techniques to isolate understudied cardiac cell populations, such as mural cells and glia. Our analyses also revealed extensive networks of intercellular communication and suggested prevalent sexual dimorphism in gene expression in the heart. This study offers insights into the structure and function of the mammalian cardiac cellulome and provides an important resource that will stimulate studies in cardiac cell biology

β1-Integrin-Mediated Uptake of Chondrocyte Extracellular Vesicles Regulates Chondrocyte Homeostasis.

Osteoarthritis (OA) is the most prevalent age-related degenerative disorder, which severely reduces the quality of life of those affected. Whilst management strategies exist, no cures are currently available. Virtually all joint resident cells generate extracellular vesicles (EVs), and alterations in chondrocyte EVs during OA have previously been reported. Herein, we investigated factors influencing chondrocyte EV release and the functional role that these EVs exhibit. Both 2D and 3D models of culturing C28I/2 chondrocytes were used for generating chondrocyte EVs. We assessed the effect of these EVs on chondrogenic gene expression as well as their uptake by chondrocytes. Collectively, the data demonstrated that chondrocyte EVs are sequestered within the cartilage ECM and that a bi-directional relationship exists between chondrocyte EV release and changes in chondrogenic differentiation. Finally, we demonstrated that the uptake of chondrocyte EVs is at least partially dependent on β1-integrin. These results indicate that chondrocyte EVs have an autocrine homeostatic role that maintains chondrocyte phenotype. How this role is perturbed under OA conditions remains the subject of future work

Limited genomic divergence between intraspecific forms of Culex pipiens under different ecological pressures

Abstract Background: Divergent selection can be a major driver of ecological speciation. In insects of medical importance, understanding the speciation process is both of academic interest and public health importance. In the West Nile virus vector Culex pipiens, intraspecific pipiens and molestus forms vary in ecological and physiological traits. Populations of each form appear to share recent common ancestry but patterns of genetic differentiation across the genome remain unknown. Here, we undertook an AFLP genome scan on samples collected from both sympatric and allopatric populations from Europe and the USA to quantify the extent of genomic differentiation between the two forms. Results: The forms were clearly differentiated but each exhibited major population sub-structuring between continents. Divergence between pipiens and molestus forms from USA was higher than in both inter- and intra-continental comparisons with European samples. The proportion of outlier loci between pipiens and molestus (≈3 %) was low but consistent in both continents, and similar to those observed between sibling species of other mosquito species which exhibit contemporary gene flow. Only two of the outlier loci were shared between inter-form comparisons made within Europe and USA. Conclusion: This study supports the molestus and pipiens status as distinct evolutionary entities with low genomic divergence. The low number of shared divergent loci between continents suggests a relatively limited number of genomic regions determining key typological traits likely to be driving incipient speciation and/or adaptation of molestus to anthropogenic habitats

Bioaccessibility and intestinal uptake of minerals from different types of home-cooked and ready-to-eat beans

Limited information exists on the bioaccessibility and intestinal uptake of essential minerals from different types of beans cooked through different cooking methods. This study aimed to estimate the in vitro bioaccessibility and intestinal uptake of the essential minerals K, Ca, Mg, Fe, Zn, Mn, Cu and Mo from four different types of beans (kidney, black, white and cowpea) cooked under different conditions (home-cooked and industrially processed canned product). Results showed that the bioaccessibility and uptake of most essential minerals is higher in canned beans. Mn was the mineral that presented the highest bioaccessibility (43–63%), and Mo had the lowest (3–36%). The highest uptake was observed for Mg (59.9%), while the lowest was found for Fe (10.5%). Regarding the type of beans, white beans presented the highest bioaccessibility and uptake for all the analyzed essential minerals and thus its consumption is preferable from a nutritional point of view.Edgar Pinto and César Oliveira acknowledge Instituto de Ciências e Tecnologias Agrárias e Agro-Alimentares da Universidade do Porto (ICETA) for their contracts NORTE-01-0145-FEDER-0001 and NORTE-01-0145-FEDER-000011, respectively. This work received financial support from the European Union (POCI/01/0145/FEDER/007265), from the European Regional Development Fund (ERDF) through COMPETE – Operational Competitiveness Programme and from national funds provided by FCT – Foundation for Science and Technology under the project UID/QUI/50006/2013.info:eu-repo/semantics/publishedVersio

Derrame pleuropericárdico: no todo es lupus

A 69-year-old woman was admitted in our hospital with dyspnoea in context of heart failure. She was diagnosed of autoimmune hemolityc anemia, treated with steroids. Echocardiography revealed a severe pleuropericardial effusion. A pericardiocentesis and thoracocentesis were performed and other test was performed due to obtain a diagnosis. The patient was diagnosed of primary effusion lymphoma associated to Epstein-Barr infection. Primary effusion lymphoma is an uncommon type of lymphoma found mainly in immunosuppressed patients positive HIV and human herpesvirus 8 infection with unfavourable prognosis. After chemotherapy treatment with R-CHOP cycles, the patient is now in remission.Mujer de 69 años que presenta cuadro clínico de disnea en el contexto de insuficiencia cardíaca aguda y tratamiento crónico con corticoides por anemia hemolítica autoinmune. En las pruebas complementarias se observa derrame pleuropericárdico severo. Ante estos hallazgos se realiza pericardiocentesis y toracocentesis y se completa estudio para descartar patología tumoral, infecciosa, tiroidea y autoinmune. Se diagnostica a la paciente de linfoma primario de cavidades, asociado a infección por virus de Epstein-Barr. Es un tipo poco frecuente de linfoma que se describe fundamentalmente en pacientes infectados por virus de la inmunodeficiencia humana y asociados al virus herpes humano tipo 8 con pronóstico muy desfavorable. Tras tratamiento quimioterápico con ciclos de R-CHOP la paciente se encuentra actualmente en remisión completa

Más allá del hipo persistente. A propósito de un caso

A 69-year-old man, after several emergency medical care admissions, and one admission to Internal Medicine Service for persistent hiccup, was been discharged without conclusive results. After 48 hours, patient showed lower limb paraesthesia and hypaesthesia, finding in physical exams pyramidalism with positive Babinski reflex and sensitive level at D5. Myelography is performed finding out extensive cervical-thoracic myelitis, indeed neuromyelitis optica is diagnosed, confirmed by the presence of the anti-aquaporin-4 antibody in blood test. Therefore, this case shows one possible atypical presentations of neuromyelitis optica.Varón de 69 años que tras varias consultas a Urgencias y un ingreso en Medicina Interna por hipo persistente, es dado de alta sin resultados concluyentes. A las 48 horas comienza con parestesias e hipoestesia en miembros inferiores, objetivando en la exploración piramidalismo con Babinski bilateral positivo y nivel sensitivo en D5. Se realiza mielografía en la que se observan signos de mielitis extensa cervicodorsal, confirmando mediante la presencia en sangre de anticuerpos antiacuaporina-4, el diagnóstico de enfermedad de Devic. Por tanto, este caso muestra una de las posibles presentaciones atípicas de la neuromielitis óptica