1,720,979 research outputs found
Direct- and spacer-coupled codrug strategies for the treatment of Alzheimer’s disease
No full textOver the last years, the ‘multi-target-directed ligand’ strategy has been
exploited by many researchers to develop novel attractive tools in the search
for new agents for Alzheimer’s disease (AD). Small molecules that concurrently
target and modulate AD multiple pathological factors can be synthesized using
such strategy. This paper will mainly focus on direct- and spacer-coupled codrug
approaches that we recently rationally used to design multifunctional molecules
able to contrast oxidative stress, neuroinflammation, glutamate toxicity, and
metal dyshomeostasis, as a function of the structural elements introduced in the
chemical framework.
Although the potential use of these strategies needs further exhaustive
studies, it may offer a promising therapeutic alternative for increasing neuronal
protection and preventing AD progression
In vitro evaluation of the potential anticancer activity of new memantin co-drugs on rat C6 glioblastoma cells
No full textSynthesis of Short Cationic Antimicrobial Peptidomimetics Containing Arginine Analogs
No full textWorldwide efforts are underway to develop new antimicrobial agents against bacterial resistance. To identify new compounds with
a good antimicrobial profile, we designed and synthesized two series of small cationic antimicrobial peptidomimetics (1–8)
containing unusual arginine mimetics (to introduce cationic charges) and several aromatic amino acids (bulky moieties to
improve lipophilicity). Both series were screened for in vitro antibacterial activity against a representative panel of Gram-positive
(Staphylococcus aureus and Staphylococcus epidermidis) and Gram-negative (Escherichia coli and Klebsiella pneumoniae) bacterial
strains, and Candida albicans. The biological screening showed that peptidomimetics containing tryptophan residues are
endowed with the best antimicrobial activity against S. aureus and S. epidermidis in respect to the other synthesized derivatives
(MIC values range 7.5–50mg/ml). Moreover, small antimicrobial peptidomimetics derivatives 2 and 5 showed an appreciable
activity against the tested Gram-negative bacteria and C. albicans. The most active compounds (1–2 and 5–6) have been tested
against Gram-positive established biofilm, too. Results showed that the biofilm inhibitory concentration values of these
compounds were never up to 200mg/ml. The replacement of tryptophan with phenylalanine or tyrosine resulted in considerable
loss of the antibacterial action (compounds 3–4 and 7–8) against both Gram-positive and Gram-negative bacterial strains.
Furthermore, by evaluating hemolytic activity, the synthesized compounds did not reveal cytotoxic activities, except for
compound 5. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.
Keywords: antimicrobial peptidomimetics; arginine analogs; antibacterial activity; antifungal activity; microbia
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
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
Neuroinflammation and endoplasmic reticulum stress are coregulated by cyclo(His-Pro) to prevent LPS neurotoxicity
No full textMany neurological and neurodegenerative diseases are associated with oxidative stress and glial inflammation,
all related to endoplasmic reticulum stress. Cyclo(His-Pro) is an endogenous cyclic dipeptide that
exerts cytoprotection by interfering with the Nrf2–NF-B systems, the former presiding the antioxidant
and the latter the pro-inflammatory cellular response. Here we investigated whether the cyclic dipeptide
inhibits glial inflammation thus reducing the detrimental effect of inflammatory neurotoxins on neurons.
We found that systemic administration of cyclo(His-Pro) exerts in vivo anti-inflammatory effects in the
central nervous system by down-regulating hepatic and cerebral TNF expression thereby counteracting
LPS-induced gliosis. Mechanistic studies indicated that the cyclic dipeptide-mediated effects are achieved
through the activation of Nrf2-driven antioxidant response and the inhibition of the pro-inflammatory
NF-B pathway. Moreover, by up-regulating Bip, cyclo(His-Pro) increases the ER stress sensitivity and
triggers the unfolded protein response to alleviate the ER stress. These results unveil a novel potential
therapeutic use of cyclo(His-Pro) against neuroinflammatory-related diseases and we might now
consider its potential anti-inflammatory role in other neuropathological conditions
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