1,721,059 research outputs found
Resveratrol and health: the starting point.
No full textCascade of youth? Resveratrol, the celebrated phytoalexin of red wine, was known to activate AMPK indirectly, but how this happened was unclear. In a paper recently published in Cell, S.-J. Park, J. H. Chung and co-workers identify the signalling cascade, which begins with the inhibition of phosphodiesterases, in particular PDE4. But questions remain, even while new perspectives open up
Mitochondrial channels: ion fluxes and more.
No full textThe field of mitochondrial ion channels has recently seen substantial progress, including the molecular identification of some of the channels. An integrative approach using genetics, electrophysiology, pharmacology, and cell biology to clarify the roles of these channels has thus become possible. It is by now clear that many of these channels are important for energy supply by the mitochondria and have a major impact on the fate of the entire cell as well. The purpose of this review is to provide an up-to-date overview of the electrophysiological properties, molecular identity, and pathophysiological functions of the mitochondrial ion channels studied so far and to highlight possible therapeutic perspectives based on current information
Synthesis of resveratrol sulfates: turning a nightmare into a dream
No full textAbstract The growing interest in the bioactivity of natural polyphenols and of their metabolites requires pure metabolites to be used in bioassays and as standards in analytical protocols. We report here the synthesis of all five resveratrol sulfates achieved using a known approach of selective protection via silyl ether and sulfation but new reaction conditions and isolation procedures, which result in simplified protocols and greatly improved yields. A rationale for the problems so far encountered in handling and isolating resveratrol sulfates is provided as well as a solution based on avoidance of low pressure conditions during purification/isolation. These conclusions are probably of more general scope and might be usefully taken into consideration for obtaining other phenolic sulfates in high yield
Nanocostrutti comprendenti nanoparticelle lipidiche solide rivestite da un guscio idrofilo
No full text
Induction of Apoptosis in Macrophages via Kv1.3 and Kv1.5 Potassium Channels.
No full textWe have previously shown that the mitochondrial potassium channel Kv1.3 (mtKv1.3) in T lymphocytes is a novel target of Bax. Mutation of Bax at lysine 128 (BaxK128E) abrogates its inhibitory effects on mtKv1.3 and prevents apoptosis. The importance of mtKv1.3 inhibition was underscored by the finding that membrane-permeant Kv1.3 inhibitors induced Bax/Bak-independent cell death and reduced the volume of an mtKv1.3-expressing tumor by 90% in a mouse model. However, the possible involvement of other Kv channels in apoptosis has not been clarified. Here we report that, like Kv1.3, Kv1.1 and Kv1.5 also interact with Bax. Transfection of Kv-deficient lymphocytes with Kv1.1 restores sensitivity to cell death in apoptosis-resistant CTLL-2 lymphocytes. SiRNA down-regulation of Kv1.3 and Kv1.5 expression in macrophages confers resistance to apoptosis. We further report that J774 macrophages express Kv1.3 and Kv1.5 in their mitochondria and that inhibition of both channels with specific membrane-permeant drugs can efficiently induce apoptosis in a macrophage cell line. Thus, our results indicate that the mechanism proposed for Kv1.3 can be extended to other Kv channels and suggest that membrane-permeant drugs may be a novel pharmacological tool for inducing apoptosis in macrophages, important players in the immune system. This result could be exploited for the depletion of tumor-associated macrophages, which have been shown to foster tumor growth
Peptides as Pharmacological Carriers to the Brain: Promises, Shortcomings and Challenges
Full text linkCentral nervous system (CNS) diseases are among the most difficult to treat, mainly because the vast majority of the drugs fail to cross the blood-brain barrier (BBB) or to reach the brain at concentrations adequate to exert a pharmacological activity. The obstacle posed by the BBB has led to the in-depth study of strategies allowing the brain delivery of CNS-active drugs. Among the most promising strategies is the use of peptides addressed to the BBB. Peptides are versatile molecules that can be used to decorate nanoparticles or can be conjugated to drugs, with either a stable link or as pro-drugs. They have been used to deliver to the brain both small molecules and proteins, with applications in diverse therapeutic areas such as brain cancers, neurodegenerative diseases and imaging. Peptides can be generally classified as receptor-targeted, recognizing membrane proteins expressed by the BBB microvessels (e.g., Angiopep2, CDX, and iRGD), "cell-penetrating peptides" (CPPs; e.g. TAT(47-57), SynB1/3, and Penetratin), undergoing transcytosis through unspecific mechanisms, or those exploiting a mixed approach. The advantages of peptides have been extensively pointed out, but so far few studies have focused on the potential negative aspects. Indeed, despite having a generally good safety profile, some peptide conjugates may display toxicological characteristics distinct from those of the peptide itself, causing for instance antigenicity, cardiovascular alterations or hemolysis. Other shortcomings are the often brief lifetime in vivo, caused by the presence of peptidases, the vulnerability to endosomal/lysosomal degradation, and the frequently still insufficient attainable increase of brain drug levels, which remain below the therapeutically useful concentrations. The aim of this review is to analyze not only the successful and promising aspects of the use of peptides in brain targeting but also the problems posed by this strategy for drug delivery
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