Publications by authors named "Luciani R"

Listening to natural auditory scenes leads to distinct neuronal activity patterns in the early visual cortex (EVC) of blindfolded sighted and congenitally blind participants. This pattern of sound decoding is organized by eccentricity, with the accuracy of auditory information increasing from foveal to far peripheral retinotopic regions in the EVC (V1, V2, and V3). This functional organization by eccentricity is predicted by primate anatomical connectivity, where cortical feedback projections from auditory and other non-visual areas preferentially target the periphery of early visual areas.

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Pteridine reductase 1 (PTR1) is a catalytic protein belonging to the folate metabolic pathway in Trypanosmatidic parasites. PTR1 is a known target for the medicinal chemistry development of antiparasitic agents against Trypanosomiasis and Leishmaniasis. In previous studies, new nitro derivatives were elaborated as PTR1 inhibitors.

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Article Synopsis
  • Researchers identified broad-spectrum anti-infective agents from a library of 456 compounds through a high-throughput screening program, focusing on compounds effective against specific parasite species.
  • Using machine learning, they characterized and synthesized 44 compounds showing strong antiparasitic properties with minimal toxicity, highlighting one promising lead with a unique chemical structure.
  • The study utilized advanced chemoinformatic and machine learning tools to handle complex data, facilitating the selection and optimization of compounds for further biological and toxicological evaluation.
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Background: Despite advance in pharmacotherapy of lipid disorders, lipoprotein apheresis (LA) plays a leading role in the management of severe hypercholesterolemia and in atherosclerosis prevention.

Methods: Aim of this study was to retrospectively evaluate Charlson Comorbidity Index (CCI), presence of major comorbidity, and/or concomitant polypharmacy (definite as 5+ drugs daily) in patients with inherited dyslipidemias on chronic LA.

Results: Since 1994, we performed more than 500 LA treatment/year and followed a total of 83 patients (age 56 [47-65] years, male 75%).

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Drugs that target human thymidylate synthase (hTS), a dimeric enzyme, are widely used in anticancer therapy. However, treatment with classical substrate-site-directed TS inhibitors induces over-expression of this protein and development of drug resistance. We thus pursued an alternative strategy that led us to the discovery of TS-dimer destabilizers.

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Background: Lipoprotein apheresis acutely increases coronary microvascular blood flow. However, measurement techniques are time-consuming, costly, and invasive. The ocular vasculature may be an appropriate surrogate and an easily accessible window to investigate the microcirculation.

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The optimization of compounds with multiple targets is a difficult multidimensional problem in the drug discovery cycle. Here, we present a systematic, multidisciplinary approach to the development of selective antiparasitic compounds. Computational fragment-based design of novel pteridine derivatives along with iterations of crystallographic structure determination allowed for the derivation of a structure-activity relationship for multitarget inhibition.

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Three open-source anti-kinetoplastid chemical boxes derived from a whole-cell phenotypic screening by GlaxoSmithKline (Tres Cantos Anti-Kinetoplastid Screening, TCAKS) were exploited for the discovery of a novel core structure inspiring new treatments of parasitic diseases targeting the trypansosmatidic pteridine reductase 1 (PTR1) and dihydrofolate reductase (DHFR) enzymes. In total, 592 compounds were tested through medium-throughput screening assays. A subset of 14 compounds successfully inhibited the enzyme activity in the low micromolar range of at least one of the enzymes from both and parasites (pan-inhibitors), or from both PTR1 and DHFR-TS of the same parasite (dual inhibitors).

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Differences in empathic abilities between acting, dance, and psychology students were explored, in addition to the appropriateness of existing empathy measures in the context of these cohorts. Students ( = 176) across Higher Education Institutions in the United Kingdom and Europe were included in the online survey analysis, consisting of the Reading the Mind in the Eyes (RME) test, the Interpersonal Reactivity Index (IRI), the Empathy Quotient (EQ), and the E-drawing test (EDT), each measuring particular facets of empathy. Based on existing evidence and our understanding of the discipline practices, we predicted that acting students would perform the best at identifying people's emotional expressions but might lack other cognitive or affective empathy skills, particularly those related to emotional reactions.

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Thymidylate synthase (TS) is a prominent drug target for different cancer types. However, the prolonged use of its classical inhibitors, substrate analogs that bind at the active site, leads to TS overexpression and drug resistance in the clinic. In the effort to identify anti-TS drugs with new modes of action and able to overcome platinum drug resistance in ovarian cancer, octapeptides with a new allosteric inhibition mechanism were identified as cancer cell growth inhibitors that do not cause TS overexpression.

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Leishmaniasis, a major health problem worldwide, has a limited arsenal of drugs for its control. The appearance of resistance to first- and second-line anti-leishmanial drugs confirms the need to develop new and less toxic drugs that overcome spontaneous resistance. In the present study, we report the design and synthesis of a novel library of 38 flavonol-like compounds and their evaluation in a panel of assays encompassing parasite killing, pharmacokinetics, genomics and ADME-Toxicity resulting in the progression of a compound in the drug discovery value chain.

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Chemical modulation of the flavonol 2-(benzo[d][1,3]dioxol-5-yl)-chromen-4-one (), a promising anti-Trypanosomatid agent previously identified, was evaluated through a phenotypic screening approach. Herein, we have performed structure-activity relationship studies around hit compound . The pivaloyl derivative () showed significant anti- activity (EC = 1.

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Human thymidylate synthase (hTS) is pivotal for cell survival and proliferation, indeed it provides the only synthetic source of dTMP, required for DNA biosynthesis. hTS represents a validated target for anticancer chemotherapy. However, active site-targeting drugs towards hTS have limitations connected to the onset of resistance.

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Thymidylate synthase (TS) is an enzyme of paramount importance as it provides the only de novo source of deoxy-thymidine monophosphate (dTMP). dTMP, essential for DNA synthesis, is produced by the TS-catalyzed reductive methylation of 2'-deoxyuridine-5'-monophosphate (dUMP) using N⁵,N-methylenetetrahydrofolate (mTHF) as a cofactor. TS is ubiquitous and a validated drug target.

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Article Synopsis
  • Researchers discovered 2-Amino-benzo[d]thiazole as a promising new structure for creating better inhibitors of pteridine reductase-1 (PTR1) and potential treatments for Trypanosoma and Leishmania infections.
  • They designed and synthesized 42 new compounds based on this structure, identifying some with strong enzyme inhibition and low toxicity against T. brucei and Leishmania species.
  • One standout compound, 2-amino-N-benzylbenzo[d]thiazole-6-carboxamide (4c), showed significant anti-parasitic effects, good safety profile, and improved oral bioavailability, suggesting its potential for further testing in living organisms.
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Fourteen lots of cooked ham in modified atmosphere packaging (CH) were analyzed within a few days from packaging (S) and at the end of the shelf-life (E), after storage at 7 °C to simulate thermal abuse. Five more lots, rejected from the market because spoiled (R), were included in the study. Quality of the products was generally compromised during the shelf life, with only 4 lots remaining unaltered.

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Background: Lipoprotein apheresis (LA) is the elective therapy for homozygous and other forms of Familial Hypercholesterolemia, Familial Combined Hypercholesterolemia, resistant/intolerant to lipid lowering drugs, and hyper-lipoproteinemia(a). Lipoprotein(a) [Lp(a)] has been classified as the most prevalent genetic risk factor for coronary artery disease and aortic valve stenosis.

Aim: Our multicenter retrospective study has the aim to analyze the incidence of adverse cardiovascular events (ACVE) before and during the LA treatment, in subjects with elevated level of Lp(a) (>60 mg/dL) [hyper-Lp(a)] and chronic ischemic heart disease.

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LR and [d-Gln]LR peptides bind the monomer-monomer interface of human thymidylate synthase and inhibit cancer cell growth. Here, proline-mutated LR peptides were synthesized. Molecular dynamics calculations and circular dichroism spectra have provided a consistent picture of the conformational propensities of the [Pro ]-peptides.

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