Search results for " DOC"
showing 10 items of 1281 documents
Famotidine inhibits toll-like receptor 3-mediated inflammatory signaling in SARS-CoV-2 infection
2021
Apart from prevention using vaccinations, the management options for COVID-19 remain limited. In retrospective cohort studies, use of famotidine, a specific oral H2 receptor antagonist (antihistamine), has been associated with reduced risk of intubation and death in patients hospitalized with COVID-19. In a case series, nonhospitalized patients with COVID-19 experienced rapid symptom resolution after taking famotidine, but the molecular basis of these observations remains elusive. Here we show using biochemical, cellular, and functional assays that famotidine has no effect on viral replication or viral protease activity. However, famotidine can affect histamine-induced signaling processes i…
Diagnostic and Therapeutic Approach to Sleep Disorders, High Blood Pressure and Cardiovascular Diseases. A Consensus Document by the Italian Society …
2021
Hypertension is a major contributor to fatal/nonfatal cardiovascular diseases, and timely identification and appropriate management of factors affecting hypertension and its control are mandatory public health issues. By inducing neurohormonal alterations and metabolic impairment, sleep disorders have an impact on a variety of cardiovascular risk factors, including hypertension, and ultimately increase the risk of cardiovascular events. There is evidence that qualitative and quantitative sleep disorders are associated with resistant hypertension and with impaired circadian blood pressure variations. However, sleep disturbances are often unrecognized, or heterogeneity exists in their managem…
Discovery of Natural Products as Novel and Potent FXR Antagonists by Virtual Screening
2018
Farnesoid X receptor (FXR) is a member of nuclear receptor family involved in multiple physiological processes through regulating specific target genes. The critical role of FXR as a transcriptional regulator makes it a promising target for diverse diseases, especially those related to metabolic disorders such as diabetes and cholestasis. However, the underlying activation mechanism of FXR is still a blur owing to the absence of proper FXR modulators. To identify potential FXR modulators, an in-house natural product database (NPD) containing over 4,000 compounds was screened by structure-based virtual screening strategy and subsequent hit-based similarity searching method. After the yeast t…
Off-Target-Based Design of Selective HIV-1 PROTEASE Inhibitors
2021
The approval of the first HIV-1 protease inhibitors (HIV-1 PRIs) marked a fundamental step in the control of AIDS, and this class of agents still represents the mainstay therapy for this illness. Despite the undisputed benefits, the necessary lifelong treatment led to numerous severe side-effects (metabolic syndrome, hepatotoxicity, diabetes, etc.). The HIV-1 PRIs are capable of interacting with “secondary” targets (off-targets) characterized by different biological activities from that of HIV-1 protease. In this scenario, the in-silico techniques undoubtedly contributed to the design of new small molecules with well-fitting selectivity against the main target, analyzing possible undesirabl…
Tryptophan-Containing Dual Neuroprotective Peptides: Prolyl Endopeptidase Inhibition and Caenorhabditis elegans Protection from β-Amyloid Peptide Tox…
2018
Neuroprotective peptides represent an attractive pharmacological strategy for the prevention or treatment of age-related diseases, for which there are currently few effective therapies. Lactoferrin (LF)-derived peptides (PKHs) and a set of six rationally-designed tryptophan (W)-containing heptapeptides (PACEIs) were characterized as prolyl endopeptidase (PEP) inhibitors, and their effect on β-amyloid peptide (Aβ) toxicity in a Caenorhabditis elegans model of Alzheimer’s disease (AD) was evaluated. Two LF-derived sequences, PKH8 and PKH11, sharing a W at the C-terminal end, and the six PACEI heptapeptides (PACEI48L to PACEI53L) exhibited significant in vitro PEP inhibition. The inhibitory pe…
Antiprotozoal and cysteine proteases inhibitory activity of dipeptidyl enoates
2018
A family of dipeptidyl enoates has been prepared and tested against the parasitic cysteine proteases rhodesain, cruzain and falcipain-2 related to sleeping sickness, Chagas disease and malaria, respectively. They have also been tested against human cathepsins B and L1 for selectivity. Dipeptidyl enoates resulted to be irreversible inhibitors of these enzymes. Some of the members of the family are very potent inhibitors of parasitic cysteine proteases displaying k2nd (M−1s−1) values of seven orders of magnitude. In vivo antiprotozoal testing was also performed. Inhibitors exhibited IC50 values in the micromolar range against Plasmodium falciparum, Trypanosoma brucei, Trypanosoma cruzi and ev…
Towards the realization of a basic professional profile model for Science, Technology and Mathematics (STEM) teachers
2017
[EN] In this work it is both discussed and provided a framework of speci c competences that may serve asa guide for setting up an ongoing process in the professional development of Science, Technology andMathematics (STEM) teachers. The fundamentals of the TPACK model serve to base the theoreticalbackground of this scheme, to which we have incorporated an additional feature which means to considerthe linguistic (L) dimension, thus transforming it into the TPACLK model. The di erent detailed profes-sional STEM capacities have been classi ed into six main sections. The two rst points discussed establishthe STEM disciplinary and didactic capacities; the third section corresponds to the role of…
An Efficient Cooperative Smearing Technique for Degraded Historical Documents Images Segmentation
2020
Segmentation is one of the critical steps in historical document image analysis systems that determines the quality of the search, understanding, recognition and interpretation processes. It allows isolating the objects to be considered and separating the regions of interest (paragraphs, lines, words and characters) from other entities (figures, graphs, tables, etc.). This stage follows the thresholding, which aims to improve the quality of the document and to extract its background from its foreground, also for detecting and correcting the skew that leads to redress the document. Here, a hybrid method is proposed in order to locate words and characters in both handwritten and printed docu…
Other-Repetition as a Resource for Participation in the Activity of Playing a Video Game
2009
This article offers an empirically based contribution to the growing body of studies using Conversation Analysis (CA) as a tool for analyzing second/foreign language learning in and through interaction. Building on a sociointeractional view of learning as grounded in the structures of participation in social activities, we apply CA methods to examine the affordances offered by interaction during the activity of playing a video game for additional language learning. We focus on one type of interactional practice, lexical and prosodic repetition, as a recurring resource through which players attend to the game and collaboratively build their understanding and experience of game events. We arg…
Readability and the Web
2012
Readability indices measure how easy or difficult it is to read and comprehend a text. In this paper we look at the relation between readability indices and web documents from two different perspectives. On the one hand we analyse how to reliably measure the readability of web documents by applying content extraction techniques and incorporating a bias correction. On the other hand we investigate how web based corpus statistics can be used to measure readability in a novel and language independent way.