1,721,004 research outputs found
18-kDa translocator protein association complexes in the brain: From structure to function
No full textThe outer mitochondrial membrane 18-kDa translocator protein (TSPO) is highly conserved in organisms of different species and ubiquitously expressed throughout tissues, including the nervous system. In the healthy adult brain, TSPO expression levels are low and promptly modulated under different pathological conditions, such as cancer, inflammatory states, and neurological and psychiatric disorders. Not surprisingly, several endogenous and synthetic molecules capable of binding TSPO have been proposed as drugs or diagnostic tools for brain diseases. The most studied biochemical function of TSPO is cholesterol translocation into mitochondria, which in turn affects the synthesis of steroids in the periphery and neurosteroids in the brain. In the last 30 years, roles for TSPO have also been suggested in other cellular processes, such as heme synthesis, apoptosis, autophagy, calcium signalling and reactive oxygen species production. Herein, we provide an overview of TSPO associations with different proteins, focusing particular attention on their related functions. Furthermore, recent TSPO-targeted therapeutic interventions are explored and discussed as prospect for innovative treatments in mental and brain diseases
Planarian Mucus: A Novel Source of Pleiotropic Cytotoxic and Cytostatic Agents against Cancer Cells
No full textBiological evolution has generated a vast array of natural compounds produced by organisms across all domains. Among these, secondary metabolites, selected to enhance an organism's competitiveness in its natural environment, make them a reservoir for discovering new compounds with cytotoxic activity, potentially useful as novel anticancer agents. Slime secretions, the first barrier between epithelial surfaces and the surrounding environment, frequently contain cytotoxic molecules to limit the growth of parasitic organisms. Planarians, freshwater Triclads, continuously secrete a viscous mucus with multiple physiological functions. The chemical composition of planarian mucus has been only partially elucidated, and there are no studies reporting its cytotoxic or cytostatic effects. In this study, we developed a protocol for collecting mucus from Dugesia japonica specimens and we demonstrated that it inhibits the growth of cancer cells by activating cytostatic and ROS-dependent cytotoxic mechanisms inducing lipid droplet accumulation and mitochondrial membrane reorganization. Although further research is needed to identify the specific chemicals responsible for the anticancer activity of planarian mucus, this work opens up numerous research avenues aimed at better understanding the mechanisms of action of this product for potential therapeutic applications
Drug Mechanism: A bioinformatic update
No full textA drug Mechanism of Action (MoA) is a complex biological phenomenon that describes how a bioactive compound produces a pharmacological effect. The complete knowledge of MoA is fundamental to fully understanding the drug activity. Over the years, many experimental methods have been developed and a huge quantity of data has been produced. Nowadays, considering the increasing omics data availability and the improvement of the accessible computational resources, the study of a drug MoA is conducted by integrating experimental and bioinformatics approaches. The development of new in silico solutions for this type of analysis is continuously ongoing; herein, an updating review on such bioinformatic methods is presented. The methodologies cited are based on multi-omics data integration in biochemical networks and Machine Learning (ML). The multiple types of usable input data and the advantages and disadvantages of each method have been analyzed, with a focus on their applications. Three specific research areas (i.e. cancer drug development, antibiotics discovery, and drug repurposing) have been chosen for their importance in the drug discovery fields in which the study of drug MoA, through novel bioinformatics approaches, is particularly productive
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
An insight into hypothesized biological mechanisms contributing to the Flash effect
No full textIn recent years, FLASH radiotherapy (FLASH RT) has gained attention in preclinical studies as a potential advancement in cancer treatment. The great advantage of FLASH RT is the ultra-fast, high doses delivery that have a similar or greater effect on cancer cells while sparing normal, healthy tissue surrounding the tumor site. This is known as the FLASH effect. However, currently, there are not enough in vitro and in vivo data to transpose FLASH RT to human trials. This mini review summarizes the available in vitro data on electron beam FLASH, focusing on possible mechanisms of the FLASH effect. Current studies have focused on various types of cancer, including lung cancer, glioblastoma, uterus adenocarcinoma, cervix carcinoma, prostate carcinoma, melanoma, breast cancer, head and neck squamous cell carcinoma, and colon adenocarcinoma. Several hypotheses have been proposed to explain the biological mechanisms contributing to the to the selective FLASH effect, including differences between healthy and cancer cells in production of reactive oxygen species and free radicals, limitation of Fenton reaction caused by high Fe2+/(3+) levels in tumor cells, and impaired DNA damage repair mechanisms occurring in cancer
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