1,721,087 research outputs found
Insights into molecular mechanisms of metallodrugs using metallomic studies
No full textMetal ions are the center of an important class of therapeutics, i.e. metallodrugs for their unique coordination geometries and redox states. Many cellular functions depend on the interaction of metal ions with proteins, as well as the transport and uptake of metals into cells, storage and secretion which are regulated by peculiar control systems. The cellular redox homeostasis is regulated by a plethora of factors including metal ions that can produce reactive radicals and its dysregulation can lead to oxidative stress as observed in pathological conditions in many diseases as cancer, cardiovascular disease, diabetes, atherosclerosis, neurological disorders (Alzheimer's, Parkinson's disease) and chronic inflammation. Omics approaches can provide in-depth insights into the mechanisms of action (MOAs) of metallo-therapeutic compounds and metallomics is a proteomic tool that allows to investigate MOAs of metallodrugs, including their physiological metabolism (e.g., cellular distribution and biotransformation) and their molecular targets. Herein, we review the most recent and significant metallomic studies concerning metallodrugs in pathological cellular conditions including oxidative stress
Are peptidomimetics the compounds of choice for developing new modulators of the JAK-STAT pathway?
No full textProtein-protein interactions (PPIs) play critical roles in a wide range of biological processes including the dysregulation of cellular pathways leading to the loss of cell function, which in turn leads to diseases. The dysfunction of several signaling pathways is linked to the insurgence of pathological processes such as inflammation, cancer development and neurodegeneration. Thus, there is an urgent need for novel chemical modulators of dysregulated PPIs to drive progress in targeted therapies. Several PPIs have been targeted by bioactive compounds, and, often, to properly cover interacting protein regions and improve the biological activities of modulators, a particular focus concerns the employment of macrocycles as proteomimetics. Indeed, for their physicochemical properties, they occupy an intermediate space between small organic molecules and macromolecular proteins and are prominent in the drug discovery process. Peptide macrocycles can modulate fundamental biological mechanisms and here we will focus on peptidomimetics active on the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathways
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
Self-assembling peptides: From design to biomedical applications
No full textSelf-assembling peptides could be considered a novel class of agents able to harvest an array of micro/nanostructures that are highly attractive in the biomedical field. By modifying their amino acid composition, it is possible to mime several biological functions; when assembled in micro/nanostructures, they can be used for a variety of purposes such as tissue regeneration and engineering or drug delivery to improve drug release and/or stability and to reduce side effects. Other significant advantages of self-assembled peptides involve their biocompatibility and their ability to efficiently target molecular recognition sites. Due to their intrinsic characteristics, self-assembled peptide micro/nanostructures are capable to load both hydrophobic and hydrophilic drugs, and they are suitable to achieve a triggered drug delivery at disease sites by inserting in their structure’s stimuli-responsive moieties. The focus of this review was to summarize the most recent and significant studies on self-assembled peptides with an emphasis on their application in the biomedical field
Proteomimetics of Natural Regulators of JAK–STAT Pathway: Novel Therapeutic Perspectives
No full textThe JAK-STAT pathway is a crucial cellular signaling cascade, including an intricate network of Protein-protein interactions (PPIs) responsible for its regulation. It mediates the activities of several cytokines, interferons, and growth factors and transduces extracellular signals into transcriptional programs to regulate cell growth and differentiation. It is essential for the development and function of both innate and adaptive immunities, and its aberrant deregulation was highlighted in neuroinflammatory diseases and in crucial mechanisms for tumor cell recognition and tumor-induced immune escape. For its involvement in a multitude of biological processes, it can be considered a valuable target for the development of drugs even if a specific focus on possible side effects associated with its inhibition is required. Herein, we review the possibilities to target JAK-STAT by focusing on its natural inhibitors as the suppressor of cytokine signaling (SOCS) proteins. This protein family is a crucial checkpoint inhibitor in immune homeostasis and a valuable target in immunotherapeutic approaches to cancer and immune deficiency disorders
Heparin-binding hemagglutinin HBHA from Mycobacterium tuberculosis affects actin polymerisation
No full textFrom peptides to small molecules: An intriguing but intricated way to new drugs
No full textA variety of peptides active in biological pathways have been identified e.g. receptor antagonists or inhibitors of protein-protein interactions and several peptide or peptide-derived compounds are on the drug market or in clinical trials. Through the rational design or the combinatorial preparation and High-throughput screening of arrays of compounds, peptides play a pivotal role for the rapid identification of ligands, but, despite these favorable properties, they often present poorer bioavailability and lower metabolic stability respect to traditional drugs. The process of conversion of a peptide in a small molecule provides the reduction of the peptide to the minimum active sequence (MAS) testing truncated peptides from the C- and N- termini alternatively. Then the influence of individual amino acid on the biological activity is determined by systematically replacing each residue in the peptide with specific amino acids. After structure-activity relationship (SAR) of each amino acid in the sequence has been assessed, the bioactive conformational flexibility is reduced by introducing constraints at various positions. These features are used for the design of a pharmacophore model in which functional groups crucial for activity are pre-positioned. Here we propose a panoramic review of the common principles for the conversion of peptides into small organic molecules and the most interesting findings in peptide-based leads of the last decades
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
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