121,800 research outputs found
Autophagy modulators for the treatment of oral and esophageal squamous cell carcinomas
No full textOral squamous cell carcinomas (OSCC) and esophageal squamous cell carcinomas (ESCC) exhibit a survival rate of less than 60% and 40%, respectively. Late-stage diagnosis and lack of effective treatment strategies make both OSCC and ESCC a significant health burden. Autophagy, a lysosome-dependent catabolic process, involves the degradation of intracellular components to maintain cell homeostasis. Targeting autophagy has been highlighted as a feasible therapeutic strategy with clinical utility in cancer treatment, although its associated regulatory mechanisms remain elusive. The detection of relevant biomarkers in biological fluids has been anticipated to facilitate early diagnosis and/or prognosis for these tumors. In this context, recent studies have indicated the presence of specific proteins and small RNAs, detectable in circulating plasma and serum, as biomarkers. Interestingly, the interplay between biomarkers (eg, exosomal microRNAs) and autophagic processes could be exploited in the quest for targeted and more effective therapies for OSCC and ESCC. In this review, we give an overview of the available biomarkers and innovative targeted therapeutic strategies, including the application of autophagy modulators in OSCC and ESCC. Additionally, we provide a viewpoint on the state of the art and on future therapeutic perspectives combining the early detection of relevant biomarkers with drug discovery for the treatment of OSCC and ESCC
Raising the bar in anticancer therapy: recent advances in, and perspectives on, telomerase inhibitors
No full textTelomerase is a ribonucleic reverse transcriptase enzyme that uses an integral RNA component as a template to add tandem telomeric DNA repeats, TTAGGG, at the 3′ end of the chromosomes. 85–90% of human tumors and their derived cell lines predominantly express high levels of telomerase, therefore contributing to cancer cell development. However, in normal cells, telomerase activity is almost always absent except in germ cells and stem cells. This differential expression has been exploited to develop highly specific and potent cancer therapeutics. In this review, we outline recent advances in the development of telomerase inhibitors as anticancer agents. This review reports recent advances in the development of telomerase inhibitors as anticancer agents and highlights the advantages of targeting telomerases in cancer therapy
Retinitis pigmentosa and retinal degenerations: deciphering pathways and targets for drug discovery and development
No full textInherited retinal diseases (IRDs) are a group of retinopathies generally caused by genetic mutations. Retinitis pigmentosa (RP) represents one of the most studied IRDs. RP leads to intense vision loss or blindness resulting from the degeneration of photoreceptor cells. To date, RP is mainly treated with palliative supplementation of vitamin A and retinoids, gene therapies, or surgical interventions. Therefore, a pharmacologically based therapy is an urgent need requiring a medicinal chemistry approach, to validate molecular targets able to deal with retinal degeneration. This Review aims at outlining the recent research efforts in identifying new drug targets for RP, especially focusing on the neuroprotective role of the Wnt/β-catenin/GSK3β pathway and apoptosis modulators (in particular PARP-1) but also on growth factors such as VEGF and BDNF. Furthermore, the role of spatiotemporally expressed G protein-coupled receptors (GPR124) in the retina and the emerging function of histone deacetylase inhibitors in promoting retinal neuroprotection will be discussed
Piero Alfredo Gianfrotta, Patrice Pomey, avec la collaboration de Filippo Coarelli, Archeologia Subacquea, storia, tecniche, scoperte e relitti, 1981
No full textRieth Éric. Piero Alfredo Gianfrotta, Patrice Pomey, avec la collaboration de Filippo Coarelli, Archeologia Subacquea, storia, tecniche, scoperte e relitti, 1981. In: Les Nouvelles de l'archéologie, n°9, Juillet-septembre 1982. Archéologie et aménagement. pp. 113-115
A light in the dark: State of the art and perspectives in optogenetics and optopharmacology for restoring vision
No full textIn the last decade, innovative therapeutic strategies against inherited retinal degenerations (IRDs) have emerged. In particular, chemical- and opto-genetics approaches or a combination of them have been identified for modulating neuronal/optical activity in order to restore vision in blinding diseases. The 'chemical-genetics approach' (optopharmacology) uses small molecules (exogenous photoswitches) for restoring light sensitivity by activating ion channels. The 'opto-genetics approach' employs light-activated photosensitive proteins (exogenous opsins), introduced by viral vectors in injured tissues, to restore light response. These approaches offer control of neuronal activities with spatial precision and limited invasiveness, although with some drawbacks. Currently, a combined therapeutic strategy (optogenetic pharmacology) is emerging. This review describes the state of the art and provides an overview of the future perspectives in vision restoration
Modulation of the Innate Immune Response by Targeting Toll-like Receptors: A Perspective on Their Agonists and Antagonists
No full textToll-like receptors (TLRs) are a class of proteins that recognize pathogen-associated molecular patterns (PAMPs) and damaged-associated molecular patterns (DAMPs), and they are involved in the regulation of innate immune system. These transmembrane receptors, localized at the cellular or endosomal membrane, trigger inflammatory processes through either myeloid differentiation primary response 88 (MyD88) or TIR-domain-containing adapter-inducing interferon-β (TRIF) signaling pathways. In the last decades, extensive research has been performed on TLR modulators and their therapeutic implication under several pathological conditions, spanning from infections to cancer, from metabolic disorders to neurodegeneration and autoimmune diseases. This Perspective will highlight the recent discoveries in this field, emphasizing the role of TLRs in different diseases and the therapeutic effect of their natural and synthetic modulators, and it will discuss insights for the future exploitation of TLR modulators in human health. © 2020 American Chemical Society
A Multi-Language Comparison of Influences on Author Verification using Character N-Grams
No full textWe create a new multi-language corpus for author verification based on Wikipedia talkpages, and evaluate the influence that differences in topic and time have on character n-gram author profiles. Topic alignment between two texts is found to increase author verification precision, and an authors writing style is found to change over time, but not more significantly after 3 years than after 1 year.Information ArchitectureWISElectrical Engineering, Mathematics and Computer Scienc
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe 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
Oxygen, carbon, and nutrient exchanges at the sediment–water interface in the Mar Piccolo of Taranto (Ionian Sea, southern Italy)
No full textIn the shallow environment, the nutrient and carbon exchanges at the sediment–water interface contribute significantly to determine the trophic status of the whole water column. The intensity of the allochthonous input in a coastal environment subjected to strong anthropogenic pressures determines an increase in the benthic oxygen demand leading to depressed oxygen levels in the bottom waters. Anoxic conditions
resulting from organic enrichment can enhance the exchange of nutrients between sediments and the overlying water. In the present study, carbon and nutrient fluxes at the sediment–water interface were measured at two experimental sites, one highly and one moderately contaminated, as reference point. In situ benthic flux measurements of dissolved species (O2, DIC, DOC, N-NO3−, N-NO2−, N-NH4+, P-PO43−, Si-Si(OH)4, H2S) were conducted using benthic chambers. Furthermore, undisturbed sediment cores were collected for
analyses of total and organic C, total N, and biopolymeric carbon (carbohydrates, proteins, and lipids) as well as of dissolved
species in porewaters and supernatant in order to calculate the diffusive fluxes. The sediments were characterized by suboxic to anoxic conditions with redox values more negative in the highly contaminated site, which was also characterized by higher biopolymeric carbon content (most of all lipids), lower C/N ratios and generally higher diffusive fluxes, which could result in a higher release of contaminants. A great difference was observed between diffusive and in situ benthic fluxes suggesting the enhancing of fluxes by bioturbation and the occurrence of biogeochemically important processes at the sediment–water interface. The multi-contamination of both inorganic and organic pollutants, in the sediments of the Mar Piccolo of Taranto (declared SIN in 1998), potentially transferable to the water column and to the aquatic trophic chain, is of serious concern for its ecological relevance, also considering the widespread fishing and mussel farming activities in the area
Geochemical signatures of intense episodic anaerobic oxidation of methane in near-surface sediments of a recently discovered cold seep (Kveithola trough, NW Barents Sea)
No full textAt cold seep environments, the detection of large 34S enrichments within bulk sulphide minerals has been frequently
used as a proxy to infer the vertical migrations of the sulphate-methane transition zone (SMTZ).
Processes related to the oxidative part of the sulphur cycle can alter the original stable sulphur isotope composition
(δ34S) of the solid sulphur phases, in particular at the sediment-water interface. Identification of paleo
and present positions of methane fronts in the sedimentary records requires the use of multiple geochemical
proxies. Authigenic enrichment of Mo has been demonstrated to represent a valid and durable tracer of the past
SMTZ depth fluctuations and of the intensities of the related methane seepages. This study is based on two
closely-spaced short cores collected from the Main Drift of the Kveithola trough, a glacially-carved depression
located in northwestern Barents Sea. Active fluid seepage has been recently reported in this area and a gas flare
was specifically observed in proximity of the sampling sites where the cores object of our study were retrieved. In
order to collect evidences of the possible occurrence of anaerobic oxidation of methane (AOM) at the sedimentwater
interface of the investigated area and infer the entity of the associated methane flux, we combined the
analyses of reduced sulphur species δ34S, total organic carbon and redox-sensitive elements. The negative δ34S
values within the extracted solid sulphur phases (up to −49.1‰ for pyritic sulphur) show that organoclastic
sulphate reduction (OSR) coupled with disproportionation of sulphur intermediates are the only active processes
in the near-surface sediments. However, moderate to strong enrichments of Mo detected in the relatively organic
carbon poor intervals of both cores and the lack of concurrent enrichments of Co, Cu, Ni, V and Zn, usually
associated to OSR-dominated environment, suggested that the sulphidic conditions favouring the Mo enrichments
were produced by AOM. Therefore, we infer that high methane flux events characterized the drift area of
the Kveithola, occasionally moving upward the SMTZ and thus inducing intense AOM in proximity of the sediment-
water interface of this part of the trough. Our results confirmed the validity of sedimentary Mo as an
indicator of the occurrence and intensity of past methane seepages
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