1,721,059 research outputs found

    ISOXADOLE DERIVATIVES AS INDUCERS OF FETAL HEMOGLOBIN IN ERYTHROID PRECURSOR CELLS FROM BETA-THALASSEMIC PATIENTS

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    The invention refers to the use of isoxazole derivatives to prepare medicament able to induce fetal hemoglobin (HbF) synthesis in β-thalassemia and sickle cell disease (SCD) patients.We recently found that isoxazole derivatives characterized by a Resorcinol portion and the C-3 amide moiety show high activity in inducing HbF synthesis in erythroid precursors cells (ErPCs) derived from β-thalassemia patients. These data were verified using ErPCs from an high number of patients with different genotypes and HbF starting levels

    The ethanol fraction from the stem of Berberis libanotica inhibits the viability of adult T cell leukemia

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    Aim. In the Mediterranean countries, several described medicinal plants are derived from Lebanon. According to Tohme et al. there are 2597 species in Lebanon. More than fifty two percent are endemic to Lebanon. In this paper we show that the ethanol fraction of the stem of Berberis libanotica is able to inhibit the viability of HTLV-1 positive (HuT-102) and HTLV-1 negative (CEM) cell lines of malignant T-cell leukemia. Methods. After traditional maceration to extract the ethanol fraction from Berberis libanotica stem, the in vitro viability was assayed. Results. The results suggest that Berberis libanotica (a Lebanese medicinal plant) contains a substantial amount of secondary metabolites such as alkaloids powerful in inhibiting the viability of HuT-102 and CEM cell lines. Conclusion. The obtained results demonstrate a novel anticancer property of Berberis libanotica stem extracts, in addition to the previously reported anti-inflammatory activity.Abi Saab S, 2008, LEBAN SCI J, V9, P99; Barbour EK, 2004, J ETHNOPHARMACOL, V93, P1, DOI 10.1016-j.jep.2004.02.027; Bazarbachi A, 2001, VIRUS RES, V78, P79, DOI 10.1016-S0168-1702(01)00286-6; Bazarbachi A, 2011, BLOOD, V118, P1736, DOI 10.1182-blood-2011-03-345702; Darwiche N, 2007, EXPERT OPIN DRUG DIS, V2, P361, DOI 10.1517-17460441.2.3.361; FOLEY GE, 1965, CANCER, V18, P522, DOI 10.1002-1097-0142(196504)18:4522::AID-CNCR28201804183.0.CO;2-J; Gritsanapan W, 2009, J HLTH RES, V23, P59; Hande KR, 1998, EUR J CANCER, V34, P1514, DOI 10.1016-S0959-8049(98)00228-7; Harakeh S, 2004, CHEM-BIOL INTERACT, V148, P101, DOI 10.1016-j.cbi.2004.05.002; Ishitsuka K, 2008, EUR J HAEMATOL, V80, P185, DOI 10.1111-j.1600-0609.2007.01016.x; Khan M, 2010, MUTAT RES-FUND MOL M, V683, P123, DOI 10.1016-j.mrfmmm.2009.11.001; Lampronti I, 2008, EVID-BASED COMPL ALT, V5, P303, DOI 10.1093-ecam-nem042; Lampronti I, 2006, INT J ONCOL, V29, P989; Lampronti I, 2005, MINERVA BIOTECH, V17, P153; Matsuoka M, 2005, RETROVIROLOGY, V2, DOI 10.1186-1742-4690-2-27; Taylor JM, 2008, APOPTOSIS, V13, P733, DOI 10.1007-s10495-008-0208-7; Tohme G, 2007, ILLUSTRATED FLORA LE, P610; Yoshida M, 2010, P JPN ACAD B-PHYS, V86, P117, DOI 10.2183-pjab.86.11712

    Fetal haemoglobin (HbF) induction as a strategy to improve life quality in thalassemia: characterisation of HbF inducing products and preclinical models to predict therapeutic response

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    Beta thalassemia is due to mutations in one or both of the beta globin genes, leading to abnormal red blood cells. The different types of beta thalassemia include: (a) Beta Thalassemia Trait, including subjects that only show microcytosis and a possible mild anemia. This gene mutation can be passed on to an individual’s children. (b) Thalassemia Intermedia, including subjects with anemia requiring medical treatment. (c) Thalassemia Major (known also as Cooley's Anemia), including subjects with anemia requiring lifelong regular blood transfusions and considerable ongoing medical care. The dividing line between thalassemia intermedia and thalassemia major is the degree of anemia and the number and frequency of blood transfusions required to treat it. Those with thalassemia intermedia may need occasional transfusions. Beta thalassemia is most common in persons of Mediterranean, African and Southeast Asian descent, where thalassemia trait affects 5 to 30 percent of persons. It has been estimated that about 1.5% of the global population are carriers of beta thalassemia trait, with about 60,000 symptomatic individuals born annually, the great majority in the developing world. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union

    A personalized medicine approach for beta-thalassemia patients: testing sirolimus in a first pilot clinical trial (sirthalaclin)

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    Beta-thalassemias are hereditary blood disorders caused by reduced or absent synthesis of hemoglobin beta chains, with variable outcomes ranging from severe anemia to clinically asymptomatic individuals. Treatment is symptomatic and thalassemia is a major unmet medical need. Survival is increased, even in patients needing transfusions, in comparison with a few years ago, but the quality of life is poor for many patients. In some patients, an anomalous expression of gamma-globin genes has been observed, with a consequent rise in Fetal Hemoglobin levels. The patients displaying a clinical phenotype known as HPFH (Hereditary Persistence of Fetal Hemoglobin) exhibit a positive clinical status. To mimick HPFH, several compounds able to induce expression of embryofetal hemoglobins (HbF) have been evaluated. Within this framework, sirolimus is particularly interesting as an inducer of HbF. It has been used for many years for different indications and the available preclinical evidence warrant the start of a clinical development plan in thalassemia. We propose a pilot clinical trial in beta-thalassemia patients, designed to evaluate the effect of sirolimus on several parameters related to red blood cell status and to the level of HbF in particular, as a first step for the full clinical development in this new indicatio

    Ultra sensitive plasmonic devices for early cancer diagnosis

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    ULTRAPLACAD aims at the development of a novel robust in vitro diagnostic system for early cancer diagnosis, prognosis, patient follow-up and therapy efficacy assessment based on molecular analysis of peripheral blood (liquid biopsy). Although the platform may find wide applications in oncology, ULTRAPLACAD will focus solely on colorectal cancer (CRC) that is the second most frequently occurring cancer in the EU with an equal distribution among women and men. ULTRAPLACAD will provide unique and up to now not existing platform for the comprehensive detection of nucleic acids and protein CRC biomarkers in blood plasma. The extremely low concentration of most cancer biomarkers in blood imposes a stringent barrier to the wide applicability of the liquid biopsy for CRC diagnosis. The ULTRAPLACAD will deliver a disruptive diagnostic platform for the analysis of cancer biomarkers in blood plasma with unprecedented sensitivity and reliability. Reaching ULTRAPLACAD goals will significantly contribute to wider spread of diagnostic and prognostic protocols based on liquid biopsy – an emerging and rapidly developing cancer diagnostic approach. The use of innovative optical analytical techniques that take advantage of plasmonic metallic nanostructures (nanostructure-enhanced surface plasmon resonance imaging -NESPRI – and plasmonenhanced fluorescence spectroscopy imaging – PEFSI) will advance the state-of-art of CRC biomarkers detection (Figure 1)

    Natural substances in the treatment of cystic fibrosis

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    The research on the biological activity of natural products and biomaterials is becoming year by year more competitive and complex, and involves experts in different research fields, including chemists, biochemists, molecular biologists, immunologists and bioinformatics. While unfractionated natural products exhibit “per se” biological properties relevant for alternative therapeutic treatments of human diseases, the identification of lead compounds within these products, the characterization of molecular targets and studies of structurally-related molecules are key processes to develop novel therapeutic strategies. Cystic fibrosis is a genetic disease caused by mutations of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. It is well established that three major fields of therapeutic intervention should be considered, targeting CFTR, bacterial infection and inflammation. In this review, we describe natural products reported to be very useful tools for correction of pathological conditions related to cystic fibrosis. The main topics are (a) CFTR potentiation and correction using natural products, (b) natural products as antibacterial agents and (c) natural products exhibiting anti-inflammatory activity. The recent issues of waste utilization and drug repurposing are also discussed in the context of the development of possible therapeutic approaches for cystic fibrosis

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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