p53 Function Re-Establishment and Apoptosis Induction in Cervical Cancer Cells

Funding Information: Funding: This work was supported by the Foundation for Science and Technology (FCT), through funds from the State Budget, and by the European Regional Development Fund through the “Pro-grama Operacional Regional do Centro (Centro 2020)—Sistema de Apoio à Investigação Científica e Tecnológica—Programas Integrados de IC&DT” (Project Centro-01-0145-FEDER-000019—C4—Centro de Competências em Cloud Computing) and the project ref: UIDB/00709/2020. This work was also supported by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB. D. Gomes also acknowledges the doctoral fellowship from FCT (ref: 2020.06792.BD). This work was also supported by the Ramalingaswami Fellowship (BT/RLF/Re-entry/64/2017), Department of Biotechnology, Govt. of India (V.K.). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Cervical cancer is the fourth leading cause of death in women worldwide, with 99% of cases associated with a human papillomavirus (HPV) infection. Given that HPV prophylactic vaccines do not exert a therapeutic effect in individuals previously infected, have low coverage of all HPV types, and have poor accessibility in developing countries, it is unlikely that HPV-associated cancers will be eradicated in the coming years. Therefore, there is an emerging need for the development of anti-HPV drugs. Considering HPV E6’s oncogenic role, this protein has been proposed as a relevant target for cancer treatment. In the present work, we employed in silico tools to discover potential E6 inhibitors, as well as biochemical and cellular assays to understand the action of selected compounds in HPV-positive cells (Caski and HeLa) vs. HPV-negative (C33A) and non-carcinogenic (NHEK) cell lines. In fact, by molecular docking and molecular dynamics simulations, we found three phenolic compounds able to dock in the E6AP binding pocket of the E6 protein. In particular, lucidin and taxifolin were able to inhibit E6-mediated p53 degradation, selectively reduce the viability, and induce apoptosis in HPV-positive cells. Altogether, our data can be relevant for discovering promising leads for the development of specific anti-HPV drugs.publishersversionpublishe

Structural signatures of water-soluble organic aerosols in contrasting environments in South America and Western Europe

This study describes and compares the key structural units present in water-soluble organic carbon (WSOC) fraction of atmospheric aerosols collected in different South American (Colombia – Medellín and Bogotá, Peru – Lima, Argentina – Buenos Aires, and Brazil – Rio de Janeiro, São Paulo, and Porto Velho, during moderate (MBB) and intense (IBB) biomass burning) and Western European (Portugal – Aveiro and Lisbon) locations. Proton nuclear magnetic resonance (1H NMR) spectroscopy was employed to assess the relative distribution of non-exchangeable proton functional groups in aerosol WSOC of diverse origin, for the first time to the authors’ knowledge in South America. The relative contribution of the proton functional groups was in the order H-C > H–C–C= > H-C-O > Ar-H, except in Porto Velho during MBB, Medellín, Bogotá, and Buenos Aires, for which the relative contribution of H-C-O was higher than that of H-C-C=. The 1H NMR source attribution confirmed differences in aging processes or regional sources between the two geographic regions, allowing the differentiation between urban combustion-related aerosol and biological particles. The aerosol WSOC in Aveiro, Lisbon, and Rio de Janeiro during summer are more oxidized than those from the remaining locations, indicating the predominance of secondary organic aerosols. Fresh emissions, namely of smoke particles, becomes important during winter in Aveiro and São Paulo, and in Porto Velho during IBB. The biosphere is an important source altering the chemical composition of aerosol WSOC in South America locations. The source attribution in Medellín, Bogotá, Buenos Aires, and Lima confirmed the mixed contributions of biological material, secondary formation, as well as urban and biomass burning emissions. Overall, the information and knowledge acquired in this study provide important diagnostic tools for future studies aiming at understanding the water-soluble organic aerosol problem, their sources and impact at a wider geographic scale.Fil: Duarte, Regina M.B.O.. Universidade de Aveiro; PortugalFil: Matos, João T.V.. Universidade de Aveiro; PortugalFil: Paula, Andreia S.. Universidade de Aveiro; PortugalFil: Lopes, Sónia P.. Universidade de Aveiro; PortugalFil: Pereira, Guilherme. Universidade de Sao Paulo; BrasilFil: Vasconcellos, Pérola. Universidade de Sao Paulo; BrasilFil: Gioda, Adriana. Universidade Federal do Rio de Janeiro; BrasilFil: Carreira, Renato. Universidade Federal do Rio de Janeiro; BrasilFil: Silva, Artur M.S.. Universidade de Aveiro; PortugalFil: Duarte, Armando C.. Universidade de Aveiro; PortugalFil: Smichowski, Patricia Nora. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rojas, Nestor. Universidad Nacional de Colombia; ColombiaFil: Sanchez Ccoyllo, Odon. No especifíca

Validation of the WHOQOL-Bref instrument in Brazilian sign language (Libras)

Purpose: the recognition of the Brazilian Sign Language (Libras) as the official language of the Brazilian deaf, in 2002, reaffirms the linguistic and cultural particularities of the deaf population. Therefore, there is a lack of a validated instrument for assessing the Quality of Life of deaf people using Libras. With authorization from the World Health Organization (WHO), a version of the WHOQOL-Bref in Libras was developed, called WHOQOL-Bref/Libras. However, its psychometric properties have not been examined as yet. Therefore, the purpose of this work is to perform the psychometric validation of the WHOQOL-Bref/Libras. Methods: WHOQOL-Bref/Libras and a sociodemographic questionnaire were applied to 311 deaf people from the five Brazilian regions. To assess temporal stability, the questionnaire was readministered to 52 deaf people, over an interval of 2 weeks. Results: WHOQOL-Bref/Libras demonstrated satisfactory psychometric values for reliability, discriminant and construct validity, temporal stability, and internal consistency. Cronbach's alpha coefficient showed satisfactory values for each of the WHOQOL-Bref domains: Physical health (0.641), Psychological (0.705), Environment (0.710), and Overall-Bref domains (0.873). The WHOQOL-Bref/Libras is the appropriate option to assess the quality of life of deaf people who communicate through Libras. Conclusion: WHOQOL-Bref/Libras had a satisfactory psychometric performance; therefore, it is a valid option that will provide autonomous participation for the deaf in quality of life investigations

Estudo do complexo valvar atrioventricular cardíaco esquerdo em búfalos (Bubalus bubalis) da raça Jafarabadi

Atrioventricular valve complex of 30 Jafarabadi water buffaloes, adult males were studied in this research with no heart diseases. The animals were obtained from a slaughterhouse in Brazilian State of Parana. The hearts were opened at the third portion affording access to the valve complex. The complexes had its area, number and type of tendinous cords submitted to analysis. The results showed that the complex is composed by two cusps and four accessory cusps, two or three papillary muscles in which 10-25 tendinous cords fix on the cusps that face the ventricle wall. The total area of the complex was on average 38.56cm², with a minimum of 24.96cm² and a maximum of 55.54cm². Statistically, no relation between the number of cords and the cusps' area where they are inserted or with the number of papillary muscle where they originated from was observed.Foram estudados os complexos valvares atrioventricular esquerdo de 30 búfalos da raça Jafarabadi, machos e adultos, sem alterações cardíacas, provenientes de abatedouros do Estado do Paraná. Os corações foram examinados em seu terço médio para acesso ao complexo valvar, que foi submetido a estudos de área, número e tipificação de cordas tendíneas. Os resultados demonstram que este complexo é formado por duas cúspides principais e quatro cúspides acessórias, apresentam em sua formação de 2-3 músculos papilares, nos quais se inserem de 10-25 cordas tendíneas, que se fixam em cúspides voltadas para a parede do ventrículo. A área total deste complexo apresenta uma média de 38,56cm² com um mínimo de 24,96cm² e um máximo de 55,54cm². Estatisticamente não há relação entre número de cordas e a área da cúspide onde estas estão inseridas, nem com o número de músculos papilares dos quais elas provem

Structural and Luminescence Properties of Silica-Based Hybrids Containing New Silylated-Diketonato Europium(III) Complex

A new betadiketonate ligand displaying a trimethoxysilyl group as grafting function and a diketone moiety as complexing site (TTA-Si = 4,4,4-trifluoro-2-(3-trimethoxysilyl)propyl)-1-3-butanedione (C4H3S)COCH[(CH2)3Si(OCH3)3]COCF3) and its highly luminescent europium(III) complex [Eu(TTA-Si)3] have been synthesized and fully characterized. Luminescent silica-based hybrids have been prepared as well with this new complex grafted on the surface of dense silica nanoparticles (28 (+/-3 nm) or on mesoporous silica particles. The covalent bonding of Eu(TTA-Si)3 inside the core of uniform silica nanoparticles (40 (+/- 5 nm) was also achieved. Luminescence properties are discussed in relation to the europium chemical environment involved in each of the three hybrids. The general methodology proposed allowed high grafting ratios and overcame chelate release and tendency to agglomeration, and it could be applied to any silica matrix (in the core or at the surface, nanosized or not, dense or mesoporous) and therefore numerous applications such as luminescent markers and luminophors could be foreseen

GAMMA-ORYZANOL HAS AN EQUIVALENT EFFICACY AS A LIPID-LOWERING AGENT COMPARED TO FIBRATE AND STATIN IN TWO DYSLIPIDEMIA MICE MODELS

Objective: A substantial fraction of the population is intolerant or does not respond well to the recommended treatments for dyslipidemia. The purpose of this study was to evaluate the efficacy ofgamma-oryzanol (γ-ORZ) treatment in acute and long-term mouse experimental models of dyslipidemia in comparison toGemfibrozil and Simvastatin. Methods: For the acute dyslipidemia-induced model, dyslipidemia was induced in 40 mice using a single intra-peritoneal administration of Triton WR-1339. For the long-termmodel, dyslipidemia was induced in 24 mice using a hypercholesterolemic diet over 14 days. Thereafter, animals were divided into different groups of treatment,and orally received treatments with gamma-oryzanol (5, 25, 50mg. kg-1), gemfibrozil or simvastatin. For biochemical analysis, glucose, total cholesterol and triacylglycerols were measured. Body weight and net food intake was registered weekly, and urea, creatinine, AST and ALT levels were evaluated. The data were analyzed by analysis of variance (ANOVA), followed by the Student-Newman-Keuls method,and p value of less than 0.05 was considered significant. Results: Only the highest dose of γ-ORZ exhibited significant protective effects. Gamma-oryzanol andGemfibrozil treatments reduced total cholesterol and triacylglycerols levels in a similar manner in the acute model. In the second model, γ-ORZ and simvastatin treatments reduced glucose and total cholesterol levels in the same way. In addition, the administration ofγ-ORZ did not cause any adverse events, or significantly altered hepatic enzymes levels, plasmatic urea or creatinine concentrations. Conclusion: The results of this study suggest that gamma-oryzanol acts as a potential lipid-lowering agent, reducing triglycerides and total cholesterol in dyslipidemia-induced models

Illness perception in tuberculosis by implementation of the Brief Illness Perception Questionnaire : a TBNET study

How patients relate to the experience of their illness has a direct impact over their behavior. We aimed to assess illness perception in patients with pulmonary tuberculosis (TB) by means of the Brief Illness Perception Questionnaire (BIPQ) in correlation with patients’ demographic features and clinical TB score. Our observational questionnaire based study included series of consecutive TB patients enrolled in several countries from October 2008 to January 2011 with 167 valid questionnaires analyzed. Each BIPQ item assessed one dimension of illness perceptions like the consequences, timeline, personal control, treatment control, identity, coherence, emotional representation and concern. An open question referred to the main causes of TB in each patient’s opinion. The over-all BIPQ score (36.25 ± 11.054) was in concordance with the clinical TB score (p ≤ 0.001). TB patients believed in the treatment (the highest item-related score for treatment control) but were unsure about the illness identity. Illness understanding and the clinical TB score were negatively correlated (p < 0.01). Only 25% of the participants stated bacteria or TB contact as the first ranked cause of the illness. For routine clinical practice implementation of the BIPQ is convenient for obtaining fast and easy assessment of illness perception with potential utility in intervention design. This time saving effective personalized approach may improve communication with TB patients and contribute to better behavioral strategies in disease control

Major discrepancy between clinical diagnosis of death and anatomopathological findings in adolescents with chronic diseases during 18-years

Objectives: To evaluate the inconsistency between clinical diagnosis of death and autopsy findings in adolescents with chronic diseases. Methods: A cross-sectional study including a sample of adolescents’ autopsies who died in a pediatric and adolescent tertiary hospital over&nbsp;18&nbsp;consecutive years. During this period, there were n&nbsp;=&nbsp;2912 deaths, and n&nbsp;=&nbsp;581/2912(20%) occurred in adolescents. Of these, n&nbsp;=&nbsp;85/581(15%) underwent autopsies and were analyzed. Further results were divided into two groups: Goldman classes&nbsp;I&nbsp;or&nbsp;II (high disagreement between main clinical diagnosis of death and anatomopathological findings, n&nbsp;=&nbsp;26) and Goldman classes&nbsp;III, IV or&nbsp;V (low or no disagreement between these two parameters, n&nbsp;=&nbsp;59). Results: Median age at death (13.5&nbsp;[10‒19] vs. 13&nbsp;[10‒19] years, p&nbsp;=&nbsp;0.495) and disease duration (22&nbsp;[0‒164]&nbsp;vs.&nbsp;20&nbsp;[0‒200] months, p&nbsp;=&nbsp;0.931), and frequencies for males (58%&nbsp;vs.&nbsp;44%, p&nbsp;=&nbsp;0.247) were similar between class I/II&nbsp;vs.&nbsp;class&nbsp;III/IV/V. The frequency of pneumonia (73%&nbsp;vs.&nbsp;48%, p&nbsp;=&nbsp;0.029), pulmonary abscess (12%&nbsp;vs.&nbsp;0%, p&nbsp;=&nbsp;0.026), as well as isolation of yeast (27%&nbsp;vs.&nbsp;5%, p&nbsp;=&nbsp;0.008), and virus (15%&nbsp;vs.&nbsp;2%, p&nbsp;=&nbsp;0.029) identified in the autopsy, were significantly higher in adolescents with Goldman class&nbsp;I/II compared to those with Goldman class&nbsp;III/IV/V. In contrast, cerebral edema was significantly lower in adolescents of the first group (4%&nbsp;vs.&nbsp;25%, p&nbsp;=&nbsp;0.018). Conclusion: This study showed that&nbsp;30% of the adolescents with chronic diseases had major discrepancies between clinical diagnosis of death and autopsy findings. Pneumonia, pulmonary abscess, as well as isolation of yeast and virus were more frequently identified at autopsy findings in the groups with major discrepancies

Organosilylated complex [Eu(TTA)₃(Bpy-Si)]: a bifunctional moiety for the engeneering of luminescent silica-based nanoparticles for bioimaging

A new highly luminescent europium complex with the formula [Eu(TTA)₃(Bpy-Si)], where TTA stands for the thenoyltrifluoroacetone, (C₄H3S)COCH₂COCF₃, chelating ligand and Bpy-Si, Bpy-CH₂NH(CH₂)₃(OEt)₃, is an organosilyldipyridine ligand displaying a triethoxysilyl group as a grafting function has been synthesized and fully characterized. This bifunctional complex has been grafted onto the surface of dense silica nanoparticles (NPs) and on mesoporous silica microparticles as well. The covalent bonding of [Eu(TTA)₃(Bpy-Si)] inside uniform Stöber silica nanoparticles was also achieved. The general methodology proposed could be applied to any silica matrix, allowed high grafting ratios that overcome chelate release and the tendency to agglomerate. Luminescent silica-based nanoparticles SiO₂-[Eu(TTA)₃(Bpy-Si)], with a diameter of 28 ± 2 nm, were successfully tested as a luminescent labels for the imaging of Pseudomonas aeruginosa biofilms. They were also functionalized by a specific monoclonal antibody and subsequently employed for the selective imaging of Escherichia coli bacteria