597 research outputs found

    Sulodexide counteracts endothelial dysfunction induced by metabolic or non-metabolic stresses through activation of the autophagic program

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    OBJECTIVE: Endothelial dysfunction (ED) predisposes to venous thrombosis (VT) and post-thrombotic syndrome (PTS), a long-term VT-related complication. Sulodexide (SDX) is a highly purified glycosaminoglycan with antithrombotic, pro-fibrinolytic and anti-inflammatory activity used in the treatment of chronic venous disease (CVD), including patients with PTS. SDX has recently obtained clinical evidence in the “extension therapy” after initial-standard anticoagulant treatment for the secondary prevention of recurrent deep vein thrombosis (DVT). Herein, we investigated how SDX counteracts ED. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVEC) were used. Metabolic and non metabolic-induced ED was induced by treating with methylglyoxal (MGO) or irradiation (IR), respectively. Bafilomycin A1 was used to inhibit autophagy. The production of reactive oxygen species (ROS), tetrazolium bromide (MTT) assay for cell viability, terminal de-oxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay for cell apoptosis, Real-time PCR and Western blot analysis for gene and protein expression were used. RESULTS: SDX protected HUVEC from MGO- or IR-induced apoptosis by counteracting the activation of the intrinsic and extrinsic caspase cascades. The cytoprotective effects of SDX resulted from a reduction in a) ROS production, b) neo-synthesis and release of pro-inflammatory cytokines (TNFα, IL1, IL6, IL8), c) DNA damage induced by MGO or IR. These effects were reduced when autophagy was inhibited. CONCLUSIONS: Data herein collected indicate the ability of SDX to counteract ED induced by metabolic or non-metabolic stresses by involving the intracellular autophagy pathway. Our experience significantly increases the knowledge of the mechanisms of action of SDX against ED and supports the use of SDX in the treatment of CVD, PTS and in the secondary prevention of recurrent DVT

    Mecanismos de transferência de massa na desidratação osmótica de goiaba em soluções de sacarose, sucralose e açúcar invertido.

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    O objetivo deste trabalho foi avaliar o efeito da concentração de soluções de sacarose, sucralose e açúcar invertido sobre a cinética da desidratação osmótica de pedaços de goiaba. Frações de 1/12 do fruto foram imersas em soluções de sacarose a 0,5 e 0,4 g mL-1, de sacarose a 0,3 g mL-1 + sucralose a 0,2 g L-1 e em xarope de açúcar invertido, a 50 ºC, por 2 h, sob agitação de 60 min. A solução de açúcar invertido promoveu maior perda de água e redução de massa nas amostras de goiaba submetidas à desidratação osmótica. O melhor desempenho foi obtido para o tratamento em solução de sacarose a 0,4 g mL-1, com perda de água e redução de massa semelhantes aos valores obtidos na imersão em solução de sacarose a 0,5 g mL-1 e ganho de sólidos similar ao observado em solução de sacarose a 0,3 g mL-1

    Biological rationale for the use of DNA methyltransferase inhibitors as new strategy for modulation of tumor response to chemotherapy and radiation

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    Epigenetic modifications play a key role in the patho-physiology of many tumors and the current use of agents targeting epigenetic changes has become a topic of intense interest in cancer research. DNA methyltransferase (DNMT) inhibitors represent a promising class of epigenetic modulators. Research performed yielded promising anti-tumorigenic activity for these agents in vitro and in vivo against a variety of hematologic and solid tumors. These epigenetic modulators cause cell cycle and growth arrest, differentiation and apoptosis. Rationale for combining these agents with cytotoxic therapy or radiation is straightforward since the use of DNMT inhibitor offers greatly improved access for cytotoxic agents or radiation for targeting DNA-protein complex. The positive results obtained with these combined approaches in preclinical cancer models demonstrate the potential impact DNMT inhibitors may have in treatments of different cancer types. Therefore, as the emerging interest in use of DNMT inhibitors as a potential chemo- or radiation sensitizers is constantly increasing, further clinical investigations are inevitable in order to finalize and confirm the consistency of current observations

    Desidratação por imersão-impregnação e secagem por convecção de goiaba.

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    O objetivo deste trabalho foi avaliar as características físico-químicas e sensoriais de goiabas in natura e submetidas à desidratação por imersão-impregnação e à secagem complementar por convecção, além de avaliar a estabilidade da cor das goiabas secadas após 30, 60 e 90 dias de armazenamento sob refrigeração. Amostras de goiaba foram imersas em soluções de sacarose a 0,4 e 0,5 g mL-1, sacarose a 0,3 g mL-1 + sucralose a 0,2 g L-1, açúcar invertido a 41% (p/p) e açúcar invertido sem diluição. Foram avaliados sólidos solúveis totais, acidez titulável, pH, cor, aroma, aparência, sabor e textura. O teor de sólidos solúveis totais das amostras aumentou linearmente em função do tempo de imersão, sem efeito significativo do tipo de açúcar empregado no preparo da solução. A preservação do teor de ácido cítrico foi mais pronunciada em soluções menos concentradas de sacarose. Amostras secadas não submetidas à desidratação osmótica exibiram maior alteração de cor do que aquelas previamente desidratadas. Soluções de sacarose são mais eficazes na estabilidade da cor do que as de açúcar invertido. As goiabas submetidas à desidratação por imersão-impregnação tiveram boa aceitação sensorial, e aquelas secadas apenas por convecção não foram aceitas pelos provadores

    Development of Technologies for the Detection of (Cyber)Bullying Actions: The BullyBuster Project

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    Bullying and cyberbullying are harmful social phenomena that involve the intentional, repeated use of power to intimidate or harm others. The ramifications of these actions are felt not just at the individual level but also pervasively throughout society, necessitating immediate attention and practical solutions. The BullyBuster project pioneers a multi-disciplinary approach, integrating artificial intelligence (AI) techniques with psychological models to comprehensively understand and combat these issues. In particular, employing AI in the project allows the automatic identification of potentially harmful content by analyzing linguistic patterns and behaviors in various data sources, including photos and videos. This timely detection enables alerts to relevant authorities or moderators, allowing for rapid interventions and potential harm mitigation. This paper, a culmination of previous research and advancements, details the potential for significantly enhancing cyberbullying detection and prevention by focusing on the system’s design and the novel application of AI classifiers within an integrated framework. Our primary aim is to evaluate the feasibility and applicability of such a framework in a real-world application context. The proposed approach is shown to tackle the pervasive issue of cyberbullying effectively

    Qualidade nutricional de goiabas submetidas aos processos de desidratação por imersão-impregnação e secagem complementar por convecção.

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    Na desidratação por imersão-impregnação há transferência de água e de compostos naturais do produto para a solução hipertônica, porém poucos trabalhos têm sido realizados para identificar e quantificar as perdas destes compostos. Sendo assim, o presente trabalho teve por objetivo avaliar as alterações nos teores dos minerais Na, K, Ca, Mg, Zn e Mn e de vitamina C em goiabas submetidas aos processos combinados de desidratação por imersão-impregnação (50 ºC por 2 horas) e secagem por convecção até teor de água de 20% b.u. Os solutos empregados foram: a sacarose, em soluções de 0,4 e 0,5 g.mL-1, e o açúcar líquido invertido, em soluções a 41% (p/p) e sem diluição. Utilizou-se ainda solução mista de sacarose a 0,3 g.mL-1 e sucralose a 0,2 g.L-1, além do tratamento controle, que consistiu apenas na secagem por convecção, empregando-se um nível de temperatura e velocidade do ar de secagem, 60 ºC e 1,25 m/s, respectivamente. O efeito das condições de armazenamento sobre a estabilidade do ácido ascórbico foi avaliado sob duas temperaturas, 7 e 25 ºC, durante 60 dias. Os resultados indicaram reduções de 20 a 64% no teor de minerais ao final da desidratação por imersão-impregnação e perdas não significativas de ácido ascórbico, exceto no tratamento com açúcar invertido sem diluição. A secagem por convecção promoveu perdas significativas de vitamina C, de 32 a 68%; os valores correspondentes para as perdas de vitamina C durante o armazenamento a 7 e 25 ºC foram de 58 a 82% e de 70 a 86%, respectivamente

    Validation of the Spanish Version of the Trauma and Loss Spectrum Self-Report (TALS-SR): A Study on Healthcare Workers Facing the COVID-19 Pandemic

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    Background: The present study aimed at reporting about the validity and reliability of the Spanish version of the Trauma and Loss Spectrum-Self Report (TALS-SR), an instrument based on a multidimensional approach to Post-Traumatic Stress Disorder (PTSD) and Prolonged Grief Disorder (PGD), including a range of threatening or traumatic experiences and significant losses, besides the spectrum of peri-traumatic stress reactions and post-traumatic stress symptoms that may occur. Methods: A sample of 87 Health Care Workers (HCWs) employed in the COVID-19 Emergency Department at the Virgen de la Arrixaca and Reina Sofia Hospitals (Murcia, Spain) during the pandemic, was consecutively recruited and fulfilled the TALS-SR. Assessments also included the Impact of Event Scale-Revised (IES-R), to examine post-traumatic stress symptoms and probable PTSD. Nineteen HCWs fulfilled the TALS-SR again after three weeks from baseline for test–retest reliability. Results: This study provides evidence of good internal consistency and test–retest reliability of the Spanish version of the TALS-SR. Strong support for the internal validity structure was obtained, with positive and significant correlations between the five symptoma- tologic domains and the symptomatologic total score. Significant and good correlations between the TALS-SR symptomatologic domains and the IES-R total and single domains’ scores were found. The Questionnaire also demonstrated to discriminate between subjects with and without PTSD, with subjects with PTSD showing significantly higher mean scores in each domain of the TALS-SR. Conclusion: This study validates the Spanish version of TALS-SR, providing a useful instrument for a spectrum approach to PTSD and confirms the potential utility of this psychometric tool in both clinical practice and research settings
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