Selective Non-nucleoside Inhibitors of Human DNA Methyltransferases Active in Cancer Including in Cancer Stem Cells

Valente, Sergio,Liu, Yiwei,Schnekenburger, Michael,Zwergel, Clemens,Cosconati, Sandro,Gros, Christina,Tardugno, Maria,Labella, Donatella,Florean, Cristina,Minden, Steven,Hashimoto, Hideharu,Chang, Yan American Chemical Society 2014 Journal of medicinal chemistry Vol.57 No.3

<P/><P>DNA methyltransferases (DNMTs) are important enzymes involved in epigenetic control of gene expression and represent valuable targets in cancer chemotherapy. A number of nucleoside DNMT inhibitors (DNMTi) have been studied in cancer, including in cancer stem cells, and two of them (azacytidine and decitabine) have been approved for treatment of myelodysplastic syndromes. However, only a few non-nucleoside DNMTi have been identified so far, and even fewer have been validated in cancer. Through a process of hit-to-lead optimization, we report here the discovery of compound <B>5</B> as a potent non-nucleoside DNMTi that is also selective toward other AdoMet-dependent protein methyltransferases. Compound <B>5</B> was potent at single-digit micromolar concentrations against a panel of cancer cells and was less toxic in peripheral blood mononuclear cells than two other compounds tested. In mouse medulloblastoma stem cells, <B>5</B> inhibited cell growth, whereas related compound <B>2</B> showed high cell differentiation. To the best of our knowledge, <B>2</B> and <B>5</B> are the first non-nucleoside DNMTi tested in a cancer stem cell line.</P>

Nutritional Evaluation of Young Bulls on Tropical Pasture Receiving Supplements with Different Protein:Carbohydrate Ratios

Valente, Eriton Egidio Lisboa,Paulino, M.F.,Barros, L.V.,Almeida, D.M.,Martins, L.S.,Cabral, C.H.A. Asian Australasian Association of Animal Productio 2014 Animal Bioscience Vol.27 No.10

The objective of this work was to evaluate the nutritional parameters of young bulls supplemented with different ratios of protein: carbohydrate on tropical pastures from 4 until 18 months old. Fifty-five non-castrated beef calves ($138.3{\pm}3.4kg$, 90 to 150 d of age) were used. The calves (young bulls) were subjected to a 430-d experimental period encompassing 4 seasons. The treatments were as follows: control, only mineral mixture; HPHC, high protein and high carbohydrate supplement; HPLC, high protein and low carbohydrate supplement; LPHC, low protein and high carbohydrate supplement; and LPLC, low protein and low carbohydrate supplement. The amount of supplement was adjusted every 28 d. Dry matter (DM) intake was higher in the dry-to-rainy transition and rainy seasons for all nutritional plans. Non-supplemented animals had lower intakes of DM and total digestible nutrients (TDN) than supplemented young bulls in all seasons. Although differences in DM intake were not observed between supplemented animals, the supplements with high carbohydrate (HPHC and LPHC) had lower forage intake during suckling (rainy-to-dry transition season) and in the rainy season. However, the HPHC treatment animals had higher intake and digestibility of neutral detergent fiber. It can be concluded that supplementation with high protein levels (supplying 50% of the crude protein requirement) provide the best nutritional parameters for grazing young bulls in most seasons, increasing intake and digestibility of diet, and these effects are more intense when associated with high carbohydrate levels level (supplying 30% TDN requirement).

Grazing Behavior and Locomotion of Young Bulls Receiving Different Nutritional Plans in a Tropical Pasture

Valente, E.E.L.,Paulino, M.F.,Detmann, E.,Filho, S.C. Valadares,Chizzotti, M.L.,Silva, A.G.,Maciel, I.F.S. Asian Australasian Association of Animal Productio 2013 Animal Bioscience Vol.26 No.12

The objectives of this study were to compare visual observation and an electronic grazing time method and to evaluate the effects of nutritional plans on intake, grazing behavior and horizontal and vertical locomotion of young bulls in a tropical pasture. Thirty-nine Nellore young bulls with an average body weight of $345{\pm}9.3$ kg kept in pasture were used. The experimental treatments consisted of: restricted: animals kept in a plot with a low mass of forage receiving mineral mixture only; control: animals receiving mineral mixture only; HPHC: a high protein and high carbohydrate supplement; HPLC: a high protein and low carbohydrate supplement; LPHC: a low protein and high carbohydrate supplement; LPLC: a low protein and low carbohydrate supplement. GPS collars equipped with activity sensors were used. Information about head position, latitude, longitude and altitude were recorded. Daytime grazing behavioral patterns monitored by a continuous focal animal recording method was compared to behavior estimated by the activity sensor. Feed intake was estimated by a marker method. The Restricted group presented lower (p<0.05) intake of dry matter and TDN. However, difference in dry matter intake was not found (p>0.05) between non-supplemented and supplemented animals. Difference was not found (p>0.05) in daytime grazing time obtained by visual observation or the activity sensor method. The restricted group showed longer (p<0.05) grazing time (9.58 h/d) than other groups, but difference was not found (p>0.05) in the grazing time between Control (8.35 h/d) and supplemented animals (8.03 h/d). The Restricted group presented lower (p<0.05) horizontal locomotion distance (2,168 m/d) in comparison to other groups (2,580.6 m/d). It can be concluded that the use of activity sensor methods can be recommended due to their being similar to visual observation and able to record 24-h/d. While supplements with high carbohydrates reduce pasture intake, they do not change grazing behavior. Moderate supplementation (until 50% of protein requirement and 30% of energy requirement) of beef cattle on tropical pasture has no effect on daily locomotion.

Peri-implant disease: what we know and what we need to know

Valente, Nicola Alberto,Andreana, Sebastiano Korean Academy of Periodontology 2016 Journal of Periodontal & Implant Science Vol.46 No.3

Peri-implant disease is a serious problem that plagues today's dentistry, both in terms of therapy and epidemiology. With the expansion of the practice of implantology and an increasing number of implants placed annually, the frequency of peri-implant disease has greatly expanded. Its clinical manifestations, in the absence of a globally established classification, are peri-implant mucositis and peri-implantitis, the counterparts of gingivitis and periodontitis, respectively. However, many doubts remain about its features. Official diagnostic criteria, globally recognized by the dental community, have not yet been introduced. The latest studies using metagenomic methods are casting doubt on the assumption of microbial equivalence between periodontal and peri-implant crevices. Research on most of the features of peri-implant disease remains at an early stage; moreover, there is not a commonly accepted treatment for it. In any case, although the evidence so far collected is limited, we need to be aware of the current state of the science regarding this topic to better understand and ultimately prevent this disease.

Inferring ethylene temporal and spatial distribution in an apple orchard ( Malus domestica Borkh): a pilot study for optimal sampling with a gas sensor

João Valente,Rodrigo Almeida,Lammert Kooistra 한국원예학회 2021 Horticulture, Environment, and Biotechnology Vol.62 No.2

Apples emit a volatile organic compounds during the ripening process named ethylene, which can be used to infer the optimalharvest time. Currently, the fruit ethylene emission is assessed in controlled facilities, thus laborious and expensive. Thisarticle pioneers the study of assessing ethylene emissions in uncontrolled environments. However, understanding how theethylene spatial temporal dynamics in an open fi eld, its still elusive. Therefore, this paper provides a model from an ( Malusdomestica Borkh) apple orchard for simulation and analysis of ethylene behaviour. We demonstrate that the model is able toexplain the ethylene emissions behaviour in an orchard fi eld when subject to diff erent wind speeds, directions and ripenessstages. Based on that we have investigated diff erent sampling schemes—regular and random—for capturing the variabilityof ethylene in an orchard using an electrochemical gas sensor. These results show that a random sampling scheme performs25% better than an equivalent regular-defi ned grid. Moreover, the measurements acquired locally in the rows tend to be 10%more reliable than in other locations from the orchard. Finally, the ethylene variability can be assessed with a confi dence of75% using 4 and 16 sampling points.

First Multi-Detector Computed Tomography Evidence of Transcatheter Pacing System Migration and Embolization into the Pulmonary Vasculature

Tullio Valente,Giorgio Bocchini,Maurizio Cappelli Bigazzi,Massimo Muto,Paolo Golino,Giacomo Sica 대한흉부외과학회 2020 Journal of Chest Surgery (J Chest Surg) Vol.53 No.5

Transcatheter leadless pacemaker dislodgment is a rare and potentially fatal complication of leadless device implantation. We present the first case of multidetector computed tomography images of leadless pacemaker migration and embolization in the pulmonary middle lobe artery. The patient was managed by percutaneous retrieval of the dislodged device and re-implantation in the appropriate position.

Experimental analysis on steel and lightweight concrete composite beams

Isabel B. Valente,Paulo J.S. Cruz 국제구조공학회 2010 Steel and Composite Structures, An International J Vol.10 No.2

The present work describes the experimental tests on steel and lightweight concrete composite beams performed at University of Minho, Portugal. The study involves tests on simply supported composite beams of 4.5 m span, with the same geometrical disposition, supports and materials. The geometrical configuration for the cross section and supports is identical for every beam, varying the shear connectors?distribution and the loading conditions. Headed studs are used to provide the connection between the steel profile and the concrete slab. The parameters in study are the stud disposition and the load distribution. The main objective is to describe the composite beams behaviour, focused on its connection, and to analyse the contribution of the different components to the beams load and deformation capacity. All the tests explored the beams maximum load and deformation capacity and different types of failure were observed.

Epigallocatechin-3-gallate prior to composite resin in abfraction lesions: a split-mouth randomized clinical trial

Alves Luísa Valente Gotardo Lara,Fracasso Lisiane Martins,Cortez Thiago Vinicius,Souza-Gabriel Aline Evangelista,Corona Silmara Aparecida Milori 대한치과보존학회 2023 Restorative Dentistry & Endodontics Vol.48 No.2

Objectives Natural extracts have been investigated as a biomimetic strategy to mechanically strengthen the collagen network and control the biodegradation of extracellular matrix. This study evaluated the effect of epigallocatechin-3-gallate (EGCG) on abfraction lesions prior to the composite resin. Materials and Methods The sample consisted of 30 patients (aged between 28 and 60 years) with abfraction lesions located in 2 homologous premolars. The teeth were randomly assigned according to dentin treatment: 0.02% EGCG solution or distilled water (control). After enamel acid etching, the solutions were applied immediately for 1 minute. The teeth were restored with Universal Adhesive (3M) and Filtek Z350 XT (3M). Analyzes were done by 2 independent examiners using modified USPHS (retention, secondary caries, marginal adaptation, and postoperative sensitivity) and photographic (color, marginal pigmentation, and anatomical form) criteria at baseline (7 days) and final (18 months). The data analysis used Friedman and Wilcoxon signed-rank tests (α = 0.05). Results At baseline, all restorations were evaluated as alpha for all criteria. After 18 months, restorations were evaluated as alpha for secondary caries, color, and marginal pigmentation. There was significant difference between baseline and 18 months (p = 0.009) for marginal adaptation and postoperative sensitivity (p = 0.029), but no significant difference were verified between treatments (p = 0.433). The EGCG group had a restoration retention rate of 93.3%, while the control group had 96.7%. Conclusions The application of EGCG solution on abfraction lesions did not significantly influence the survival of the restorations based on clinical and photographic criteria. Objectives Natural extracts have been investigated as a biomimetic strategy to mechanically strengthen the collagen network and control the biodegradation of extracellular matrix. This study evaluated the effect of epigallocatechin-3-gallate (EGCG) on abfraction lesions prior to the composite resin. Materials and Methods The sample consisted of 30 patients (aged between 28 and 60 years) with abfraction lesions located in 2 homologous premolars. The teeth were randomly assigned according to dentin treatment: 0.02% EGCG solution or distilled water (control). After enamel acid etching, the solutions were applied immediately for 1 minute. The teeth were restored with Universal Adhesive (3M) and Filtek Z350 XT (3M). Analyzes were done by 2 independent examiners using modified USPHS (retention, secondary caries, marginal adaptation, and postoperative sensitivity) and photographic (color, marginal pigmentation, and anatomical form) criteria at baseline (7 days) and final (18 months). The data analysis used Friedman and Wilcoxon signed-rank tests (α = 0.05). Results At baseline, all restorations were evaluated as alpha for all criteria. After 18 months, restorations were evaluated as alpha for secondary caries, color, and marginal pigmentation. There was significant difference between baseline and 18 months (p = 0.009) for marginal adaptation and postoperative sensitivity (p = 0.029), but no significant difference were verified between treatments (p = 0.433). The EGCG group had a restoration retention rate of 93.3%, while the control group had 96.7%. Conclusions The application of EGCG solution on abfraction lesions did not significantly influence the survival of the restorations based on clinical and photographic criteria.

Impact of Acupuncture Intervention on the Pain Intensity of Patients Treated at a Tertiary Hospital in Brazil

Natália F. Valente,Eliezer de Sousa Cardoso,Juliana A. da Silva Rezende,Jeferson A. Santos 사단법인약침학회 2020 Journal of Acupuncture & Meridian Studies Vol.13 No.5

Background: Nowadays, in western societies, acupuncture is widely used over the control of pain and this analgesic approach is still the most studied aspect of acupuncture. Several studies have shown that most patients go through a significant pain decrease soon after the first sessions of acupuncture. Objectives: This research has as a goal the evaluation on the effect of acupuncture treatment regarding the relief of pain intensity of different etiologies, through the visual analog scale. Methods: This research constitutes a retrospective, descriptive study, carried out with 449 patients attended in the Institute Hospital de Base of the Federal District, in Brasilia citye Brazil. Every data was gathered from our own form, with detailed clinical history which included age, marital status, work activity, reason for referral to acupuncture, main and secondary complaints, pain intensity evaluated by the Visual Analog Scale (VAS), number of sessions completed and drug therapy. All data was organized in the Microsoft Excel and processed in the Statistical Package for the Social Sciences (SPSS), version 20.0. Results: Regarding the main complaint, the mean pain decreased from 7.3 (initial VAS) to 3.2 (final VAS), a reduction that meant more than 50% relief in pain intensity. This 50% reduction in initial pain was also observed in secondary complaints (initial VAS = 6.5 and final VAS = 3.1). Conclusions: The results of this research suggest that acupuncture treatment was effective in relieving pain intensity, providing a 50% reduction on the visual analogue scale, in relation to painful complaints of different etiologies.

Peri-implant disease: what we know and what we need to know

Nicola Alberto Valente,Sebastiano Andreana 대한치주과학회 2016 Journal of Periodontal & Implant Science Vol.46 No.3

Peri-implant disease is a serious problem that plagues today's dentistry, both in terms of therapy and epidemiology. With the expansion of the practice of implantology and an increasing number of implants placed annually, the frequency of peri-implant disease has greatly expanded. Its clinical manifestations, in the absence of a globally established classification, are peri-implant mucositis and peri-implantitis, the counterparts of gingivitis and periodontitis, respectively. However, many doubts remain about its features. Official diagnostic criteria, globally recognized by the dental community, have not yet been introduced. The latest studies using metagenomic methods are casting doubt on the assumption of microbial equivalence between periodontal and peri-implant crevices. Research on most of the features of periimplant disease remains at an early stage; moreover, there is not a commonly accepted treatment for it. In any case, although the evidence so far collected is limited, we need to be aware of the current state of the science regarding this topic to better understand and ultimately prevent this disease.