1,720,981 research outputs found
Targeting Tau Protein with Proximity Inducing Modulators: A New Frontier to Combat Tauopathies
No full textDysregulation of correct protein tau homeostasis represents the seed for the development of several devastating central nervous system disorders, known as tauopathies, that affect millions of people worldwide. Despite massive public and private support to research funding, these diseases still represent unmet medical needs. In fact, the tau-targeting tools developed to date have failed to translate into the clinic. Recently, taking advantage of the modes that nature uses to mediate the flow of information in cells, researchers have developed a new class of molecules, called proximity-inducing modulators, which exploit spatial proximity to modulate protein function(s) and redirect cellular processes. In this perspective, after a brief discussion about tau protein and the classic tau-targeting approaches, we will discuss the different classes of proximity-inducing modulators developed so far and highlight the applications to modulate tau protein's function and tau-induced toxicity
A nutraceutical based approach to reduce cholesterolaemia in patients previously intolerant of more than a statin: a pilot study
No full textQuinolinetrione-tacrine hybrids as multi-target-directed ligands against Alzheimer's disease
Full text linkMulti-target drug discovery is one of the most active fields in the search for new drugs against Alzheimer's disease (AD). This is because the complexity of AD pathological network might be adequately tackled by multitarget-directed ligands (MTDLs) aimed at modulating simultaneously multiple targets of such a network. In a continuation of our efforts to develop MTDLs for AD, we have been focusing on the molecular hybridization of the acetylcholinesterase inhibitor tacrine with the aim of expanding its anti-AD profile. Herein, we manipulated the structure of a previously developed tacrine-quinone hybrid (1). We designed and synthesized a novel set of MTDLs (2-6) by replacing the naphthoquinone scaffold of 1 with that of 2,5,8-quinolinetrione. The most interesting hybrid 3 inhibited cholinesterase enzymes at nanomolar concentrations. In addition, 3 exerted antioxidant effects in menadione-induced oxidative stress of SH-SY5Y cells. Importantly, 3 also showed low hepatotoxicity and good anti-amyloid aggregation properties. Remarkably, we uncovered the potential of the quinolinetrione scaffold, as a novel anti-amyloid aggregation and antioxidant motif to be used in further anti-AD MTDL drug discovery endeavors
A nutraceutical based approach to reduce cholesterolemia in patients previously intolerant to more than a statin: a pilot study
No full textThis study was aimed at evaluating the tolerabili-ty of a nutraceutical combination with anticholesterolaemic action in patients intolerant of statin treatment. A total of 32 hypercholesterolaemic patients, all intolerant to at least two statin treatments, were enrolled in the ambulatory service.
None of the enrolled patients was diabetic or undergoing secondary prevention of cardiovascular disease. Patients
consumed one yoghurt with 2 g of added phytosterols each morning (Pro-Activ, Unilever, Milan, Italy) and one tablet of a registered combined nutraceutical (Armolipid Plus, Rottapharm, Monza, Italy). We tested the efficacy of the treatment after 4 and 6 months. One tablet of Armolipid Plus contains: berberine 500 mg, monacolin 3 mg, and poli- cosanol 10 mg. After 3 months of treatment the patients showed a significant decrease in total cholesterol, low-den- sity lipoprotein cholesterol and triglycerides, and a significant increase in the plasma level of high-density lipoprotein cholesterol. These results were maintained after 6 months of treatment without a significant change in the mean values
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Cashew nut shell liquid (Cnsl) as a source of drugs for alzheimer’s disease
Full text linkAlzheimer’s disease (AD) is a complex neurodegenerative disorder with a multifaceted pathogenesis. This fact has long halted the development of effective anti-AD drugs. Recently, a therapeutic strategy based on the exploitation of Brazilian biodiversity was set with the aim of discovering new disease-modifying and safe drugs for AD. In this review, we will illustrate our efforts in developing new molecules derived from Brazilian cashew nut shell liquid (CNSL), a natural oil and a byproduct of cashew nut food processing, with a high content of phenolic lipids. The rational modification of their structures has emerged as a successful medicinal chemistry approach to the development of novel anti-AD lead candidates. The biological profile of the newly developed CNSL derivatives towards validated AD targets will be discussed together with the role of these molecular targets in the context of AD pathogenesis
Variations on the Author
Full text link“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
Full text linkWe 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
A nutraceutical based approach to reduce cholesterolemia in patients previously intolerant to more than a statin: a pilot study.
No full textThis study was aimed at evaluating the tolerability of a nutraceutical combination with anticholesterolaemic action in patients intolerant of statin treatment. A total of 32 hypercholesterolaemic patients, all intolerant to at least two statin treatments, were enrolled in the ambulatory service. None of the enrolled patients was diabetic or undergoing secondary prevention of cardiovascular disease. Patients consumed one yoghurt with 2 g of added phytosterols each morning (Pro-Activ, Unilever, Milan, Italy) and one tablet of a registered combined nutraceutical (Armolipid Plus, Rottapharm, Monza, Italy). We tested the efficacy of the treatment after 4 and 6 months. One tablet of Armolipid Plus contains: berberine 500 mg, monacolin 3 mg, and policosanol 10 mg. After 3 months of treatment the patients showed a significant decrease in total cholesterol, low-density lipoprotein cholesterol and triglycerides, and a significant increase in the plasma level of high-density lipoprotein cholesterol. These results were maintained after 6 months of treatment without a significant change in the mean values
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