Venetoclax in relapsed/refractory blastic plasmacytoid dendritic cell neoplasm with central nervous system involvement : a case report and review of the literature

Background: We describe a patient with blastic plasmacytoid dendritic cell neoplasm with central nervous system involvement and the outcome of venetoclax use in this setting. Case presentation: A 54-year-old Caucasian male was referred to the Haematology Unit with an enlarged inguinal lymph node which was diagnostic of a blastic plasmacytoid dendritic cell neoplasm. The staging revealed disseminated disease (skin, visceral, lymph nodes, and bone marrow). He received chemotherapy with an acute myeloid leukaemia-like regime. Afterwards, he underwent allogeneic haematopoietic stem cell transplantation, though it was not successful, showing a relapse 14 months later with hepatic and central nervous system dissemination. Intrathecal chemotherapy was administered, and venetoclax (anti-bcl2 agent) was started in an off-label indication based on most recent literature. The disease halted its course for 3 months. In the end, the patient's disease progressed and so he succumbed due to infectious complications. Conclusions: Venetoclax monotherapy seems not enough to control the disease progression under CNS involvement and other treatments should be investigated

Bone marrow fibrosis, sequence variant of asxl1, and Sjögren syndrome : A case report

Only proven pathogenic mutations associated with myeloid neoplasms are key to establish the clonal nature of the bone marrow fibrosis. In cases with genetic variants of uncertain meaning, the clinical picture may be required to rule out secondary causes. Only proven pathogenic mutations associated with myeloid neoplasms are key to establish the clonal nature of the bone marrow fibrosis. In cases with genetic variants of uncertain meaning, the clinical picture may be required to rule out secondary causes

Silent T-cell receptor cutaneous T-cell lymphoma associated to a clonal plasma cell proliferation

Within T-cell lymphomas (TCL) there are 2 entities expressing gamma-delta TCR: hepatosplenic gamma-delta T-cell lymphoma (HSGDTL) and the primary cutaneous gamma-delta T-cell lymphoma (PCGDTL). PCGDTL is a rare form of Tcell lymphoma with specific tropism for skin that have a dismal prognosis. Although even rarer, there have been reports of TCL with loss of expression of the TCR, which have been termed peripheral TCL TCR-silent type. We report the case of a cutaneous TCR-silent type lymphoma associated to a clonal plasma cell proliferation with an ominous outcome that led to a lot of discussion in its classification. Due to the aggressiveness of the disease and the scant evidence about therapy in this strange entity the outcome was fatal. We report a unique case of a TCR-silent cutaneous TCL with an exceptional histopathology, prolonged clinical evolution and a subsequent plasma cell clonal expansion

Aprenentatge autònom de l'alumne i eines per al docent mitjançant l'ús de GeoGebra. Assignatures de Matemàtiques I i II dels Graus d’ADE i d’ECO de la Universitat de Barcelona

Línies d’innovació vinculades: 216231 - Moodle / 201995 - Avaluació formativa / 235623 - Project-based learning, PBL / 020691 - Estudi de casos / 025424 – SimulacionsL’objectiu del nostre projecte ha estat millorar la docència de les assignatures de Matemàtiques dels Graus d’Economia (ECO) i d’Administració i Direcció d’Empreses (ADE), introduint a la docència el software gratuït GeoGebra. El projecte va sorgir en el context de la implantació dels graus, en un moment en què vèiem que ja no podríem seguir fent les classes de pràctiques a les aules d’informàtica amb el programa Derive, que disposaríem de menys hores de docència i que a les aules només hi hauria un ordinador per al professor i un canó de projecció. En aquelles circumstàncies vam pensar que la capacitat de GeoGebra per donar vida a funcions i vectors podia ajudar-nos a explicar els conceptes teòrics de les assignatures de Matemàtiques d’una manera tan atractiva com intuïtiva. Hem elaborat un conjunt de materials (applets) per a les assignatures de Matemàtiques I i Matemàtiques II dels graus d’ADE i d’ECO. Gràcies a la plataforma Moodle hem pogut posar aquestes applets a disposició d’alumnes i professors

Student’s autonomous learning and tools for teachers by means of the use of GeoGebra. Mathematics I and II subjects of the degrees in ADE and ECO of the University of Barcelona

The objective of our project has been to improve the teaching in mathematics subjects of the degrees in Economics (ECO) and Business management (ADE) by incorporating the GeoGebra free software. The project started when university degrees were being implemented. At that time, we realized that we could no longer use the Derive software because the practical lectures in the computer rooms were cancelled and only the teacher's computer attached to a projector remained. On the top of that, the time devoted to lectures was reduced. Under those constraints, we thought that the ability of GeoGebra to give functions and vectors life could help us in explaining the theoretical concepts of the mathematics subjects in an appealing and intuitive manner. We have created several applets for the subjects Mathematics I and Mathematics II of the degrees in ECO and ADE. Thanks to the Moodle platform we have been able to put these applets at students’ and teachers’ disposal

The SMAD2/3 interactome reveals that TGFβ controls m6A mRNA methylation in pluripotency.

The TGFβ pathway has essential roles in embryonic development, organ homeostasis, tissue repair and disease. These diverse effects are mediated through the intracellular effectors SMAD2 and SMAD3 (hereafter SMAD2/3), whose canonical function is to control the activity of target genes by interacting with transcriptional regulators. Therefore, a complete description of the factors that interact with SMAD2/3 in a given cell type would have broad implications for many areas of cell biology. Here we describe the interactome of SMAD2/3 in human pluripotent stem cells. This analysis reveals that SMAD2/3 is involved in multiple molecular processes in addition to its role in transcription. In particular, we identify a functional interaction with the METTL3-METTL14-WTAP complex, which mediates the conversion of adenosine to N6-methyladenosine (m6A) on RNA. We show that SMAD2/3 promotes binding of the m6A methyltransferase complex to a subset of transcripts involved in early cell fate decisions. This mechanism destabilizes specific SMAD2/3 transcriptional targets, including the pluripotency factor gene NANOG, priming them for rapid downregulation upon differentiation to enable timely exit from pluripotency. Collectively, these findings reveal the mechanism by which extracellular signalling can induce rapid cellular responses through regulation of the epitranscriptome. These aspects of TGFβ signalling could have far-reaching implications in many other cell types and in diseases such as cancer.We thank Cambridge Genomic Services for help in next generation sequencing. The work was 203 supported by the European Research Council starting grant “Relieve IMDs” (L.V., S.B., A.B., 204 P.M.); the Cambridge University Hospitals National Institute for Health Research Biomedical 205 Research Center (L.V., J.K., A.S.L.); the Wellcome Trust PhD program (A.O., L.Y.); a British 206 Heart Foundation PhD studentship (FS/11/77/39327 to A.B.); a Grant-in-Aid for JSPS Fellows 207 (16J08005 to S.N.); and a core support grant from the Wellcome Trust and Medical Research 208 Council to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute

Aprendizaje autónomo del alumno y herramientas para el docente mediante el uso de GeoGebra. Asignaturas de Matemáticas I y II de los Grados de ADE y de ECO de la Universidad de Barcelona

El objetivo de nuestro proyecto ha sido mejorar la docencia de las asignaturas de Matemáticas de los Grados de Economía (ECO) y de Administración y Dirección de Empresas (ADE), introduciendo en la docencia el software gratuito GeoGebra. El proyecto surgió en el contexto de la implantación de los grados, en un momento en que veíamos que ya no podríamos seguir impartiendo las clases de prácticas en las aulas de informática con el programa Derive, que dispondríamos de menos horas de docencia y que en las aulas solo habría un ordenador para el profesor y un cañón de proyección. En aquellas circunstancias pensamos que la capacidad de GeoGebra para dar vida a funciones y vectores podía ayudarnos a explicar los conceptos teóricos de las asignaturas de Matemáticas de una manera tan atractiva como intuitiva. Hemos elaborado un conjunto de materiales (applets) para las asignaturas de Matemáticas I y Matemáticas II de los grados de ADE y de ECO. Gracias a la plataforma Moodle hemos podido poner estas applets a disposición de alumnos y profesores

Berberine, a popular dietary supplement for human and animal health: Quantitative research literature analysis a review

Berberine is an alkaloid with a wide range of reported beneficial health effects. The current work provides an extensive literature analysis on berberine. Bibliometric data were identified by means of the search string TOPIC=(berberin* OR umbellatine*), which yielded 5,547 publications indexed in the Web of Science Core Collection electronic database. The VOSviewer software generated bubble maps to visualize semantic terms with citation results. The ratio of original articles to reviews was 13.6:1. The literature has been growing more quickly since the 2010s. Major contributing countries were China, the United States, India, Japan, and South Korea. Most of the publications appeared in journals specialized in pharmacology pharmacy, biochemistry molecular biology, chemistry, and plant science. Some of the frequently mentioned chemicals/chemical classes were alkaloid, palmatine, jatrorrhizine, coptisine, isoquinoline, and sanguinarine. The prevalent medical conditions under investigation included Alzheimers disease, cancer, diabetes, and obesity.Acknowledge the support by the Polish KNOW (LeadingNational Research Centre) Scientific Consortium “Healthy Animal-Safe Food,” decision of Ministry of Science and Higher Education No. 05-1/KNOW2/2015 and the European Union under the European Regional Development Fund (Homing/2017-4/41). Antoni Sureda has been supported by the Institute of Health Carlos III (Project CIBEROBN CB12/03/30038). Joanna Feder-Kubis was financed by the Polish Ministry of Science and Higher Education for the Faculty of Chemistry of Wrocław University of Science and Technology.info:eu-repo/semantics/publishedVersio

Epigenetic Activation of SOX11 in Lymphoid Neoplasms by Histone Modifications

Recent studies have shown aberrant expression of SOX11 in various types of aggressive B-cell neoplasms. To elucidate the molecular mechanisms leading to such deregulation, we performed a comprehensive SOX11 gene expression and epigenetic study in stem cells, normal hematopoietic cells and different lymphoid neoplasms. We observed that SOX11 expression is associated with unmethylated DNA and presence of activating histone marks (H3K9/14Ac and H3K4me3) in embryonic stem cells and some aggressive B-cell neoplasms. In contrast, adult stem cells, normal hematopoietic cells and other lymphoid neoplasms do not express SOX11. Such repression was associated with silencing histone marks H3K9me2 and H3K27me3. The SOX11 promoter of non-malignant cells was consistently unmethylated whereas lymphoid neoplasms with silenced SOX11 tended to acquire DNA hypermethylation. SOX11 silencing in cell lines was reversed by the histone deacetylase inhibitor SAHA but not by the DNA methyltransferase inhibitor AZA. These data indicate that, although DNA hypermethylation of SOX11 is frequent in lymphoid neoplasms, it seems to be functionally inert, as SOX11 is already silenced in the hematopoietic system. In contrast, the pathogenic role of SOX11 is associated with its de novo expression in some aggressive lymphoid malignancies, which is mediated by a shift from inactivating to activating histone modifications

Vitamin D deficiency causes inward hypertrophic remodeling and alters vascular reactivity of rat cerebral arterioles

BACKGROUND AND PURPOSE: Vitamin D deficiency (VDD) is a global health problem, which can lead to several pathophysiological consequences including cardiovascular diseases. Its impact on the cerebrovascular system is not well understood. The goal of the present work was to examine the effects of VDD on the morphological, biomechanical and functional properties of cerebral arterioles. METHODS: Four-week-old male Wistar rats (n = 11 per group) were either fed with vitamin D deficient diet or received conventional rat chow with per os vitamin D supplementation. Cardiovascular parameters and hormone levels (testosterone, androstenedione, progesterone and 25-hydroxyvitamin D) were measured during the study. After 8 weeks of treatment anterior cerebral artery segments were prepared and their morphological, biomechanical and functional properties were examined using pressure microangiometry. Resorcin-fuchsin and smooth muscle actin staining were used to detect elastic fiber density and smooth muscle cell counts in the vessel wall, respectively. Sections were immunostained for eNOS and COX-2 as well. RESULTS: VDD markedly increased the wall thickness, the wall-to-lumen ratio and the wall cross-sectional area of arterioles as well as the number of smooth muscle cells in the tunica media. As a consequence, tangential wall stress was significantly lower in the VDD group. In addition, VDD increased the myogenic as well as the uridine 5'-triphosphate-induced tone and impaired bradykinin-induced relaxation. Decreased eNOS and increased COX-2 expression were also observed in the endothelium of VDD animals. CONCLUSIONS: VDD causes inward hypertrophic remodeling due to vascular smooth muscle cell proliferation and enhances the vessel tone probably because of increased vasoconstrictor prostanoid levels in young adult rats. In addition, the decreased eNOS expression results in endothelial dysfunction. These morphological and functional alterations can potentially compromise the cerebral circulation and lead to cerebrovascular disorders in VDD