An experimental target-based platform in yeast for screening Plasmodium vivax deoxyhypusine synthase inhibitors.

The enzyme deoxyhypusine synthase (DHS) catalyzes the first step in the post-translational modification of the eukaryotic translation factor 5A (eIF5A). This is the only protein known to contain the amino acid hypusine, which results from this modification. Both eIF5A and DHS are essential for cell viability in eukaryotes, and inhibiting DHS is a promising strategy to develop new therapeutic alternatives.

Hazardous element inertisation in vitrified silicate ceramics: Effect of different matrices.

The ceramic industry is a production sector that can efficiently recycle its own processing residues, achieving a reuse index of almost 100%. Recently, the range of waste from other industrial sectors that can be used as secondary raw materials in ceramic bodies has expanded. However, such an expansion potentially introduces hazardous components.

The joint action of yeast eisosomes and membraneless organelles in response to ethanol stress.

Elevated ethanol concentrations in yeast affect the plasma membrane. The plasma membrane in yeast has many lipid-protein complexes, such as Pma1 (MCP), Can1 (MCC), and the eisosome complex. We investigated the response of eisosomes, MCPs, and membraneless structures to ethanol stress.

Analytical Validation of a Telomerase Reverse Transcriptase (TERT) Promoter Mutation Assay.

Context: Telomerase reverse transcriptase (TERT) promoter-mutated thyroid cancers are associated with a decreased rate of disease-free and disease-specific survival. High-quality analytical validation of a diagnostic test promotes confidence in the results that inform clinical decision-making.

Objective: This work aimed to demonstrate the analytical validation of the Afirma TERT promoter mutation assay.

Enhanced dissolution of anticancer drug letrozole from mesoporous zeolite clinoptilolite.

High dissolution of anticancer drugs directly adsorbed onto porous carriers is indispensable for the development of drug delivery systems with high bioavailability. We report direct adsorption/loading of the anticancer drug letrozole (LTZ) onto the clinoptilolite (CLI) zeolite after the surface activation.In vitroLTZ dissolution from the CLI zeolites reached 95 % after 23 h in an acidic medium, being faster than the dissolution of the pure LTZ molecules.

Early changes in S100B maternal blood levels can predict fetal intrauterine growth restriction.

Objectives: Intrauterine growth restriction (IUGR) represents one of the main causes of perinatal mortality and morbidity. Nowadays, IUGR early diagnosis is mandatory in order to limit the occurrence of multiorgan failure, especially the brain. Therefore, we investigated whether longitudinal S100B assessment in maternal blood could be a trustable predictor of IUGR.

Impact of septic episodes caused by Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa in a tertiary hospital: clinical and economic considerations in years 2018-2020.

Objective: To evaluate incidence, therapy and antibiotic resistance trends in septic episodes caused by three multi-drug resistant bacteria in a tertiary hospital, by also estimating their economic impact.

Methods: An observational, retrospective-cohort analysis was based on data related to patients admitted to the "SS. Antonio e Biagio e Cesare Arrigo" Hospital in Alessandria (Italy) between 2018 and 2020, that developed sepsis from multi-drug resistant bacteria of the examined species.

Porcelain versus Porcelain Stoneware: So Close, So Different. Sintering Kinetics, Phase Evolution, and Vitrification Paths.

Five porcelain and porcelain stoneware bodies were investigated to compare sintering mechanisms and kinetics, phase and microstructure evolution, and high temperature stability. All batches were designed with the same raw materials and processing conditions, and characterized by optical dilatometry, XRF, XRPD-Rietveld, FEG-SEM and technological properties. Porcelain and porcelain stoneware behave distinctly during sintering, with the convolution of completely different phase evolution and melt composition/structure.

Prp8 Intein: An In Vivo Target-Based Drug Screening System in to Identify Protein Splicing Inhibitors and Explore Its Dynamics.

Inteins are genetic mobile elements that are inserted within protein-coding genes, which are usually housekeeping genes. They are transcribed and translated along with the host gene, then catalyze their own splicing out of the host protein, which assumes its functional conformation thereafter. As Prp8 inteins are found in several important fungal pathogens and are absent in mammals, they are considered potential therapeutic targets since inhibiting their splicing would selectively block the maturation of fungal proteins.

VNTR Polymorphism in Intron 4 of the eNOS Gene and the Risk of Gastrointestinal Bleeding: A Case-control Study.

Background And Aims: Considering the lack of knowledge regarding the influence of the variable number of repeats of 27 pb in intron 4 (4b/4a VNTR - rs61722009) of the endothelial nitric oxide synthase (eNOS) on the drug response, we assessed the influence of this polymorphism for the risk of upper gastrointestinal bleeding (UGIB).

Methods: A case-control study, including 200 cases and 706 controls, was conducted in a Brazilian hospital complex. Cases were participants with UGIB diagnosis.

S100B Maternal Blood Levels in Gestational Diabetes Mellitus Are Birthweight, Gender and Delivery Mode Dependent.

Gestational Diabetes Mellitus (GDM) is one of the main causes of perinatal mortality/morbidity. Today, a parameter offering useful information on fetal central nervous system (CNS) development/damage is eagerly awaited. We investigated the role of brain-protein S100B in the maternal blood of GDM pregnancies by means of a prospective case-control study in 646 pregnancies (GDM: = 106; controls: = 530).

Yeast Double Transporter Gene Deletion Library for Identification of Xenobiotic Carriers in Low or High Throughput.

The routes of uptake and efflux should be considered when developing new drugs so that they can effectively address their intracellular targets. As a general rule, drugs appear to enter cells via protein carriers that normally carry nutrients or metabolites. A previously developed pipeline that searched for drug transporters using Saccharomyces cerevisiae mutants carrying single-gene deletions identified import routes for most compounds tested.

The Methionine 549 and Leucine 552 Residues of Friedelin Synthase from Are Important for Substrate Binding Specificity.

Friedelin, a pentacyclic triterpene found in the leaves of the Celastraceae species, demonstrates numerous biological activities and is a precursor of quinonemethide triterpenes, which are promising antitumoral agents. Friedelin is biosynthesized from the cyclization of 2,3-oxidosqualene, involving a series of rearrangements to form a ketone by deprotonation of the hydroxylated intermediate, without the aid of an oxidoreductase enzyme. Mutagenesis studies among oxidosqualene cyclases (OSCs) have demonstrated the influence of amino acid residues on rearrangements during substrate cyclization: loss of catalytic activity, stabilization, rearrangement control or specificity changing.

Detection of Saint Louis encephalitis virus in two Brazilian states.

We describe the circulation of Saint Louis encephalitis virus (SLEV) in two Brazilian States during outbreaks of Dengue and Zika viruses. We detected the virus in a patient from Araraquara, State of São Paulo, and in patients and in a mosquito pool of Culex quinquefasciatus from Sinop, State of Mato Grosso. Phylogenetic analysis grouped samples from this study within genotype V, which are closely related to other strains that previously circulated in other parts of the country.

Neural networks and hospital length of stay: an application to support healthcare management with national benchmarks and thresholds.

Background: The problem of correct inpatient scheduling is extremely significant for healthcare management. Extended length of stay can have negative effects on the supply of healthcare treatments, reducing patient accessibility and creating missed opportunities to increase hospital revenues by means of other treatments and additional hospitalizations.

Methods: Adopting available national reference values and focusing on a Department of Internal and Emergency Medicine located in the North-West of Italy, this work assesses prediction models of hospitalizations with length of stay longer than the selected benchmarks and thresholds.

Effect of probiotic, prebiotic, and synbiotic on the gut microbiota of autistic children using an in vitro gut microbiome model.

Imbalances in gut microbiota composition occur in individuals with autism spectrum disorder (ASD). The administration of probiotics, prebiotics, and synbiotics is emerging as a potential and promising strategy for regulating the gut microbiota and improving ASD-related symptoms. We first investigated the survival of the probiotics Limosilactobacillus (L.

Silencing matrix metalloproteinase-13 (Mmp-13) reduces inflammatory bone resorption associated with LPS-induced periodontal disease in vivo.

Objectives: The aim of this study was to evaluate the effect of specific inhibition of MMP-13 on inflammation and inflammatory bone resorption in a murine model of lipopolysaccharide (LPS)-induced periodontitis.

Materials And Methods: Periodontitis was induced in mice by micro-injections of LPS into the gingival tissues adjacent to the palatal surfaces of maxillary molars twice a week for 15 days. Matrix metalloproteinase-13 (Mmp-13) shRNA or a specific biochemical inhibitor were also injected into the same sites in alternating days with the LPS injections.

Structural features and development of an assay platform of the parasite target deoxyhypusine synthase of Brugia malayi and Leishmania major.

Deoxyhypusine synthase (DHS) catalyzes the first step of the post-translational modification of eukaryotic translation factor 5A (eIF5A), which is the only known protein containing the amino acid hypusine. Both proteins are essential for eukaryotic cell viability, and DHS has been suggested as a good candidate target for small molecule-based therapies against eukaryotic pathogens. In this work, we focused on the DHS enzymes from Brugia malayi and Leishmania major, the causative agents of lymphatic filariasis and cutaneous leishmaniasis, respectively.

Trypanosomatid selenophosphate synthetase structure, function and interaction with selenocysteine lyase.

Eukaryotes from the Excavata superphylum have been used as models to study the evolution of cellular molecular processes. Strikingly, human parasites of the Trypanosomatidae family (T. brucei, T.

The hospital care of patients with cancer: a retrospective analysis of the characteristics of their hospital stay in comparison with other medical conditions.

Purpose: Hospital admission is a frequent occurrence among patients with cancer, and a significant proportion of patients admitted to medical units have cancer. Their hospital stay has features that may be different compared with patients without cancer. We performed a retrospective analysis of the characteristics of patients with cancer admitted for medical conditions.

Cetirizine Reduces Gabapentin Plasma Concentrations and Effect: Role of Renal Drug Transporters for Organic Cations.

Gabapentin (GBP) is an organic cation mainly eliminated unchanged in urine, and active drug secretion has been suggested to contribute to its renal excretion. Our objective was to evaluate the potential drug-drug interaction between GBP and cetirizine (CTZ), an inhibitor of transporters for organic cations. An open-label, 2-period, crossover, nonrandomized clinical trial was conducted in patients with neuropathic pain to evaluate the effect of CTZ on GBP pharmacokinetics.