Poly(vinyl chloride) Films Incorporated with Antioxidant ZnO-Flavonoid Nanoparticles: A Strategy for Food Preservation.

Antioxidant films were prepared using poly(vinyl chloride) (PVC) incorporated with 0.5% or 1.0% zinc oxide (ZnO)-flavonoid (quercetin or morin) nanoparticles (NPZnO-Q% or NPZnO-M%) via the casting method. NP incorporation within the polymer matrix influenced the structural, morphological, optical, and thermal properties of the PVC-based films, as well as their antioxidant activity as assessed using the DPPH radical scavenging method. Our results indicated that increasing ZnO-flavonoid NP concentration increased films thickness, while reducing ultraviolet light (UV) transmittance but conserving transparency. The presence of NPZnO-Q% or NPZnO-M% improved the surface uniformity and thermal stability of the active films. In terms of antioxidant activity, there was an enhancement in the DPPH radical scavenging capacity (PVC/ZnO-Q1.0% > PVC/ZnO-Q0.5% > PVC/ZnO-M0.5% > PVC/ZnO-M1.0% > PVC), suggesting that the packaging can help protect food from oxidative processes. Therefore, these antioxidant films represent an innovative strategy for using as active food packaging material, especially intended for aiding in quality preservation and extending the shelf life of fatty foods.

Withaphysalin Derivatives from Iochroma arborescens Induce Antiproliferative and Antimigratory Activities in vitro.

Withanolides are steroidal lactones commonly found in plants of the Solanaceae family that have significant medicinal value. In this study, three withanolides extracted from Iochroma arborescens leaves were isolated and characterized. These included withaphysalin F (3: ) and two newly identified epimeric compounds: 18R- and 18S-O-methyl-withaphysalin F (1: and 2: ). Their structures were elucidated by NMR, IR, MS, CD, and X-ray diffraction analysis, and their potential against cell proliferation and migration was investigated. The cytotoxic assay revealed activity against different tumor and non-tumor cell lines. (18S)-O-methyl-withaphysalin F (2: ) presented cell death effects after at least 6 hours of exposure. MDA-MB-231 cells were exposed to 0.06 and 0.6 µM of (18S)-O-methyl-withaphysalin F (2: ), and reductions in cell adhesion, migration, and clonogenicity were observed. Morphological analysis revealed negative regulation in filopodia, salience, and roughness, as well as alterations in cellular microarchitecture. These results provide clues as to the effects of (18S)-O-methyl-withaphysalin F (2: ), allowing new molecular modifications to improve potency and selectivity and increase our antineoplastic arsenal.

The role of light emitting diode in wound healing: A systematic review of experimental studies.

Wounds represent a growing global issue demanding increased attention. To expedite wound healing, technologies are under development, and light emitting diode (LED) devices of varying wavelengths are being explored for their stimulating influence on the healing process. This article presents a systematic literature review aiming to compile, organize, and analyze the impacts of LED devices on wound healing. This review is registered on the PROSPERO platform [CRD42023403870]. Two blinded authors conducted searches in the Pubmed, Web of Science, Scopus, Embase, and ScienceDirect databases. In vitro and in vivo experimental studies assessing LED utilization in the wound healing process were included. The search yielded 1010 studies, of which 27 were included in the review. It was identified that LED stimulates different healing pathways, promoting enhanced cell proliferation and migration, angiogenesis stimulation, increased collagen deposition, and modulation of the inflammatory response. Thus, it can be concluded that the LED stimulates cellular and molecular processes contingent on the utilized parameters. The effects depend on the standards used. Cell migration and proliferation were better influenced by green and red LED. The extracellular matrix components and angiogenesis were regulated by all wavelengths and the modulation of inflammation was mediated by green, red, and infrared LEDs.

Astaxanthin induces autophagy and apoptosis in murine melanoma B16F10-Nex2 cells and exhibits antitumor activity in vivo.

Countless efforts have been made to prevent and suppress the formation and spread of melanoma. Natural astaxanthin (AST; extracted from the alga Haematococcus pluvialis) showed an antitumor effect on various cancer cell lines due to its interaction with the cell membrane. This study aimed to characterize the antitumor effect of AST against B16F10-Nex2 murine melanoma cells using cell viability assay and evaluate its mechanism of action using electron microscopy, western blotting analysis, terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay, and mitochondrial membrane potential determination. Astaxanthin exhibited a significant cytotoxic effect in murine melanoma cells with features of apoptosis and autophagy. Astaxanthin also decreased cell migration and invasion in vitro assays at subtoxic concentrations. In addition, assays were conducted in metastatic cancer models in mice where AST significantly decreased the development of pulmonary nodules. In conclusion, AST has cytotoxic effect in melanoma cells and inhibits cell migration and invasion, indicating a promising use in cancer treatment.

Implicações físicas no aparelho estomatognático e emocionais nos atendimentos odontológicos de mulheres vítimas de violência: revisão integrativa da literatura / Physical implications on the stomatognathic system and emotional implications in dental care for women victims of violence: integrative review of the literature

Infelizmente os casos de violência contra a mulher aumentam a cada dia. Neste contexto, o entendimento das implicações físicas e emocionais de tais eventos se torna fundamental na equipe multiprofissional de cuidados em saúde, que inclui o cirurgião-dentista. O objetivo deste trabalho foi levantar os principais agravos em saúde bucal relacionados a casos de violência contra a mulher, além de mapear comportamentos que sejam comuns em vítimas de abusos no momento da consulta odontológica. Foi realizada uma revisão integrativa da literatura com buscas nas bases de dados Pubmed e Scielo, de artigos dos últimos cinco anos, buscando responder à seguinte pergunta de estudo: "Quais as principais alterações físicas no sistema estomatognático e as alterações emocionais mais frequentes em mulheres vítimas de violência doméstica?". Após a aplicação dos critérios de inclusão e exclusão, 13 artigos foram selecionados para a análise. Percebe-se que as lesões em face são comuns em mulheres vítimas de violência, e os dentes não são constantemente acometidos. Em relação às questões emocionais, a consulta odontológica se configura um gatilho de ansiedade para mulheres que sofrem/sofreram algum tipo de violência. Mais estudos são necessários nesta temática que transcende o âmbito jurídico e como uma questão de saúde pública precisa de uma abordagem multi e interdisciplinar, incluindo a Odontologia

Unfortunately, cases of violence against women are increasing every day. In this context, understanding the physical and emotional implications of such events becomes fundamental in the multidisciplinary health care team, which includes the dentist. The objective of this work was to identify the main oral health problems related to cases of violence against women, in addition to mapping behaviors that are common in victims of abuse at the time of dental consultation. An integrative review of the literature was carried out with searches in the Pubmed and Scielo databases, for articles from the last five years, seeking to answer the following study question: "What are the main physical changes in the stomatognathic system and the most frequent emotional changes in women? victims of domestic violence?" After applying the inclusion and exclusion criteria, 13 articles were selected for analysis. It is clear that injuries to the face are common in women who are victims of violence, and the teeth are not constantly affected. In relation to emotional issues, the dental appointment is an anxiety trigger for women who suffer/have suffered some type of violence. More studies are needed on this topic, which transcends the legal scope and, as a public health issue, requires a multi- and interdisciplinary approach, including dentistry

Odontologia hospitalar no ambiente digital: o que se pública sobre esta habilitação? / Hospital dentistry in the digital environment: what is published about this qualification?

Objetivo: O objetivo deste trabalho foi caracterizar as publicações sobre odontologia hospitalar disponíveis em páginas da internet e em páginas do Instagram, além de avaliar a qualidade dos conteúdos disponíveis do ponto de vista da evidência científica e do uso de referências. Métodos: Foi realizado um estudo transversal e exploratório. A partir da pesquisa da chave de busca "odontologia hospitalar" foram localizadas páginas do Instagram e da Internet via Google. Resultados: No Instagram foram localizadas 15 páginas que atendiam aos critérios de inclusão, e as últimas 5 publicações foram analisadas (n=75). Para o Google foram avaliados conteúdos que correspondessem à projeto de lei, entre os primeiros 25 resultados da pesquisa, já que se trata dos mais relevantes a partir da marcação do algoritmo. Percebeu-se que o uso de referências não é frequente nem nas publicações do Instagram, tampouco nos conteúdos da Internet. Tal fato é tão importante, que os resultados deste trabalho demonstram essa urgência na mudança de cenário dos conteúdos publicados na rede mundial de computadores. Conclusão: Nesse sentido, os professores e os próprios conselhos podem atuar como bússolas, na orientação da divulgação e consumo de conteúdo aos estudantes e aos profissionais de saúde.(AU)

Aim: The objective of this study was to characterize the publications on hospital dentistry available on websites and Instagram pages, in addition to evaluating the quality of the available content from the point of view of scientific evidence and the use of references. Methods: A cross-sectional and exploratory study was carried out. From the research of the search key "hospital dentistry", Instagram and Internet pages were located via Google. Results: On Instagram, 15 pages that met the inclusion criteria were located, and the last 5 publications were analyzed (n=75). For Google, content that corresponded to the bill was evaluated, among the first 25 search results, since these are the most relevant based on the algorithm's marking. It was noticed that the use of references is not frequent either in Instagram publications or in Internet content. This fact is so important that the results of this work demonstrate this urgency in changing the scenario of content published on the World Wide Web. Conclusion: In this sense, professors and the councils themselves can act as compasses, guiding the dissemination and consumption of content to students and health professionals. (AU)

PLP2-derived peptide Rb4 triggers PARP-1-mediated necrotic death in murine melanoma cells.

Malignant melanoma is the main cause of death in patients with skin cancer. Overexpression of Proteolipid protein 2 (PLP2) increased tumor metastasis and the knockdown of PLP2 inhibited the growth and metastasis of melanoma cells. In the present work, we studied the antitumor activity of peptide Rb4 derived from protein PLP2. In vitro, Rb4 induced F-actin polymerization, prevented F-actin depolymerization and increased the ER-derived cytosolic calcium. Such effects were associated with necrosis of murine melanoma B16F10-Nex2 cells and with inhibition of the viability of human cancer cell lines. Loss of plasma membrane integrity, dilation of mitochondria, cytoplasm vacuolation and absence of chromatin condensation characterized tumor cell necrosis. Cleavage of PARP-1 and inhibition of RIP1 expression were also observed. In vivo, peptide Rb4 reduced the lung metastasis of tumor cells and delayed the subcutaneous melanoma growth in a syngeneic model. Rb4 induced the expression of two DAMPs molecules, HMGB1 and calreticulin, in B16F10-Nex2. Our results suggest that peptide Rb4 acts directly on tumor cells inducing the expression of DAMPs, which trigger the immunoprotective effect in vivo against melanoma cells. We suggest that peptide Rb4 is a promising compound to be developed as an anticancer drug.

Percepção e conhecimento de odontopediatras sobre o uso de coroas pré-fabricadas de aço e zircônia na reabilitação de dentes decíduos / Perception and knowledge of pediatric dentists about the use of prefabricated steel and zirconia crowns in the rehabilitation of deciduous teeth

Objetivo: O presente trabalho tem como objetivo avaliar o conhecimento dos odontopediatras e suas percepções, conhecendo as dificuldades que estes encontram frente ao desafio da reabilitação de dentes decíduos. Métodos: A pesquisa foi realizada por meio da aplicação de questionários on-line e a análise estatística foi descritiva e comparativa, com tabelas de frequência para as variáveis quantitativas. O teste não paramétrico de Qui-quadrado foi utilizado para estimar a associação entre as diferentes categorias dos dados e em todo o estudo, estipulou-se o nível de significância em 5%. Resultados: Os resultados da pesquisa mostraram que a maioria dos entrevistados conhecem as coroas pré-fabricadas de aço, porém sua aplicação em atendimentos de crianças com extensas destruições coronárias limita-se a 34,1% destes profissionais, sendo que a baixa utilização se deve à dificuldade de aquisição do material e falta de habilidade técnica. Já com relação às coroas pré-fabricadas de zircônia, 82,4% das odontopediatras as conhecem, mas a grande maioria não as utiliza devido à dificuldade de aquisição, falta de habilidade técnica e o seu alto custo. Não foi encontrada associação entre a dificuldade de planejamento dos casos e a consideração estética e o âmbito de trabalho do entrevistado, bem como o fato de conhecer as coroas pré-fabricadas e utilizá-las. Conclusão: Conclui-se que os materiais reabilitadores, como coroas pré-fabricadas de aço e de zircônia, são de certa forma bem conhecidos pelos odontopediatras, mas sua utilização em reabilitação de dentes decíduos ainda é limitada.

Aim: The present study aims to evaluate the knowledge of pediatric dentists and their perceptions, knowing the difficulties they face in the challenge to rehabilitate deciduous teeth. Methods: This study was carried out through the application of online questionnaires. The statistical analysis was descriptive and comparative, with frequency tables for the quantitative variables. The non-parametric chi-square test was used to estimate the association between the different categories of data, and the significance level was set at 5%. Results:The survey results showed that most respondents know about prefabricated steel crowns, but their application in the care of children with extensive coronary destruction is limited to 34.1% of these professionals. The low use is due to the difficulty of acquiring the material and the lack of technical skills. It was found that 82.4% of the pediatric dentists have knowledge about prefabricated zirconia crowns, but the vast majority do not use them due to the difficulty of acquisition, their lack of technical skills, and the product's high cost. No association was found between the difficulty of planning the cases and the esthetic consideration and sphere of work of the interviewee, nor regarding the fact of their having knowledge about the prefabricated crowns and using them. Conclusion: It can therefore be concluded that rehabilitation materials, such as prefabricated steel and zirconia crowns, are well-known by pediatric dentists, but their use in the rehabilitation of deciduous teeth is still limited.

Synthetic enzyme-catalyzed multicomponent reaction for Isoxazol-5(4H)-one Syntheses, their properties and biological application; why should one study mechanisms?

In this work, we describe the application of a synthetic enzyme (synzyme) as the catalyst to promote the multicomponent synthesis of isoxazol-5(4H)-one derivatives. The catalytic system could be used up to 15 times without any notable loss of its activity. Some derivatives showed fluorescence and their photophysical data were evaluated. The mechanism of the reaction was, for the first time, investigated and, among the three reaction pathway possibilities, only one was operating under the developed conditions. ESI-MS(/MS) allowed for both the simultaneous monitoring of the multicomponent reaction (MCR) and the proposition of a kinetic model to explain the transformation. The kinetic model pointed firmly to only one reaction pathway and helped to discard the other two possibilities. The antimicrobial abilities of all synthesized derivatives against Gram-positive and Gram-negative strains were also evaluated. The abilities of functional chromophores (fluorescent compounds) as live cell-imaging probes were verified and one of the multicomponent adducts could stain early endosomes selectively in bioimaging experiments.

Tomographic score (RAD-Covid Score) to assess the clinical severity of the novel coronavirus infection

ABSTRACT Objectives: The severity of pulmonary Covid-19 infection can be assessed by the pattern and extent of parenchymal involvement observed in computed tomography (CT), and it is important to standardize the analysis through objective, practical, and reproducible systems. We propose a method for stratifying the radiological severity of pulmonary disease, the Radiological Severity Score (RAD-Covid Score), in Covid-19 patients by quantifying infiltrate in chest CT, including assessment of its accuracy in predicting disease severity. Methods: This retrospective, single-center study analyzed patients with a confirmed diagnosis of Covid-19 infection by real-time reverse-transcriptase polymerase chain reaction, who underwent chest CT at hospital admission between March 6 and April 6, 2020. CT scans were classified as positive, negative, or equivocal, and a radiological severity score (RAD-Covid Score) was assigned. Clinical severity was also assessed upon hospital admission. Results: 658 patients were included. Agreement beyond chance (kappa statistic) for the RAD-Covid Score was almost perfect among observers (0.833), with an overall agreement of 89.5%. The RAD-Covid Score was positively correlated with clinical severity and death, i.e., the higher the RAD-Covid Score, the greater the clinical severity and mortality. This association proved independent of age and comorbidities. Accuracy of this score was 66.9%. Conclusions: The RAD-Covid Score showed good accuracy in predicting clinical severity at hospital admission and mortality in patients with confirmed Covid-19 infection and was an independent predictor of severity.

Well Defined Poly(Methyl Methacrylate)-Fe3O4/Poly(Vinyl Pivalate) Core-Shell Superparamagnetic Nanoparticles: Design and Evaluation of In Vitro Cytotoxicity Activity Against Cancer Cells.

The objective of this work is to develop and characterize polymeric nanoparticles with core-shell morphology through miniemulsion polymerization combined with seeded emulsion polymerization, aiming at the application in the treatment of vascular tumors via intravascular embolization. The synthesis of the core-shell nanocomposites was divided into two main steps: (i) Formation of the core structure, consisting of poly(methyl methacrylate)/magnetic oxide coated with oleic acid (OM-OA) via miniemulsion and (ii) shell structure produced through seeded emulsion polymerization of vinyl pivalate. Nanocomposites containing about 8 wt.% of OM-OA showed high colloidal stability, mean diameter of 216.8 nm, spherical morphology, saturation magnetization (Ms) of 4.65 emu·g-1 (57.41 emu·g-1 of Fe3O4), preserved superparamagnetic behavior and glass transition temperature (Tg) of 111.8 °C. TEM micrographs confirmed the obtaining of uniformly dispersed magnetic nanoparticles in the PMMA and that the core-shell structure was obtained by seeded emulsion with Ms of 1.35 emu·g-1 (56.25 emu·g-1 of Fe3O4) and Tg of 114.7 °C. In vitro cytotoxicity assays against murine tumor of melanoma (B16F10) and human Keratinocytes (HaCaT) cell lines were carried out showing that the core-shell magnetic polymeric materials (a core, consisting of poly(methyl methacrylate)/Fe3O4 and, a shell, formed by poly(vinyl pivalate)) presented high cell viabilities for both murine melanoma tumor cell lines, B16F10, and human keratinocyte cells, HaCaT.

EIF2α phosphorylation is regulated in intracellular amastigotes for the generation of infective Trypanosoma cruzi trypomastigote forms.

Trypanosomatids regulate gene expression mainly at the post-transcriptional level through processing, exporting and stabilising mRNA and control of translation. In most eukaryotes, protein synthesis is regulated by phosphorylation of eukaryotic initiation factor 2 (eIF2) at serine 51. Phosphorylation halts overall translation by decreasing availability of initiator tRNAmet to form translating ribosomes. In trypanosomatids, the N-terminus of eIF2α is extended with threonine 169 the homologous phosphorylated residue. Here, we evaluated whether eIF2α phosphorylation varies during the Trypanosoma cruzi life cycle, the etiological agent of Chagas' disease. Total levels of eIF2α are diminished in infective and non-replicative trypomastigotes compared with proliferative forms from the intestine of the insect vector or amastigotes from mammalian cells, consistent with decreased protein synthesis reported in infective forms. eIF2α phosphorylation increases in proliferative intracellular forms prior to differentiation into trypomastigotes. Parasites overexpressing eIF2αT169A or with an endogenous CRISPR/Cas9-generated eIF2αT169A mutation were created and analysis revealed alterations to the proteome, largely unrelated to the presence of µORF in epimastigotes. eIF2αT169A mutant parasites produced fewer trypomastigotes with lower infectivity than wild type, with increased levels of sialylated mucins and oligomannose glycoproteins, and decreased galactofuranose epitopes and the surface protease GP63 on the cell surface. We conclude that eIF2α expression and phosphorylation levels affect proteins relevant for intracellular progression of T. cruzi.

Adrenal function evaluation in critically ill dogs with low doses of synthetic ACTH / Avaliação da função adrenal em cães portadores de doenças críticas com baixa dose de ACTH sintético

The hypothalamus-pituitary-adrenal axis function may be impaired in patients with critical illnesses, especially cases of sepsis, named critical illness-related corticosteroid insufficiency (CIRCI). This study examined the function of the hypothalamic-pituitary-adrenal axis in normal dogs (n = 10) and dogs with critical diseases (n = 16), through determinations of endogenous ACTH (adrenocorticotropic hormone), basal cortisol and cortisol after stimulation in low doses of synthetic ACTH (1.0µg/kg/IV). The stimulation test with ACTH dose tested was verified as effective for evaluation of adrenal function in healthy and sick dogs. Ill dogs differed from healthy dogs by presenting higher basal cortisol values. Eight sick dogs presented a decrease in endogenous ACTH, basal cortisol, or Δ-cortisol. No significant differences were found between the control groups and critically ill dogs for the values of endogenous ACTH, cortisol after stimulation or Δ-cortisol. We concluded that the stimulation test with low-dose ACTH was effective for evaluation of adrenal function, as well as the fact that a considerable portion of critically ill dogs studied here, especially with sepsis, had evidence of inadequate corticosteroid response to stress.(AU)

A função do eixo hipotálamo-hipófise-adrenal pode estar comprometida em pacientes com doenças críticas, em especial casos de sepse, sendo nomeada de Insuficiência Corticosteroide Relacionada à Doença Crítica (ICRDC). O presente trabalho analisou a função do eixo hipotálamo-hipófise-adrenal em cães normais (n=10) e cães portadores de doenças críticas (n=16), por meio de determinações de ACTH (hormônio adrenocorticotrófico) endógeno, de cortisol basal e de cortisol após estímulo com baixa dose de ACTH sintético (1,0µg/kg/IV). Constatou-se que o teste de estimulação com ACTH na dose testada se mostrou eficaz para avaliação da função adrenal em cães sadios e doentes. Os cães doentes diferiram dos sadios ao apresentar valores maiores de cortisol basal. Oito cães doentes apresentaram diminuição do ACTH endógeno, do cortisol basal ou do Δ-cortisol. Não foram encontradas diferenças significativas entre os grupos Controle e Criticamente enfermos para os valores de ACTH endógeno, cortisol após estimulação ou Δ-cortisol. Concluiu-se que o teste de estimulação com baixa dose de ACTH mostrou-se eficaz para avaliação da função adrenal, assim como, uma parcela considerável da população de cães críticos aqui estudados, em especial com sepse, apresentaram evidências de resposta corticosteroide inadequada frente ao estresse.(AU)

Preparation of terpolymer capsules containing Rosmarinus officinalis essential oil and evaluation of its antifungal activity.

The essential oil from Rosmarinus officinalis presents antifungal activity and is used in industry as a natural preserving agent. However, essential oils are unstable compounds. So, the encapsulation of essential oils is a technique used to protect it, minimizing degradation and reducing undesired interaction with the other formulation components. Thus, this work focuses on the synthesis of terpolymeric capsules containing essential oil from Rosmarinus officinalis, aiming to use it as an antifungal component in cosmetics. The capsules were obtained via terpolymerization of methyl methacrylate, styrene and methacrylic acid in a dispersed phase polymerization process. The properties of the polymers and the fungicide activity were evaluated. The studied essential oil presented a Minimum Inhibitory Concentration (MIC) ranging from 2.25 to 4.5 mg mL-1 and a Minimum Fungicidal Concentration (MFC) from 4.5 to 9.0 mg mL-1 for strains of Candida albicans, Candida glabrata and Candida parapsilosis, and after the encapsulation process, the antifungal activity of the oil was maintained. Additionally, cytotoxicity assays against fibroblast cell lines and human keratinocytes showed that the polymeric nanocapsules containing Rosmarinus officinalis essential oil can be regarded as a very promising material intended for cosmetics and drug delivery applications.

Immunomodulatory Protective Effects of Rb9 Cyclic-Peptide in a Metastatic Melanoma Setting and the Involvement of Dendritic Cells.

The cyclic VHCDR3-derived peptide (Rb9) from RebMab200 antibody, directed to a NaPi2B phosphate-transport protein, displayed anti-metastatic melanoma activity at 50-300 µg intraperitoneally injected in syngeneic mice. Immune deficient mice failed to respond to the peptide protective effect. Rb9 induced increased CD8+ T and low Foxp3+ T cell infiltration in lung metastases and high IFN-γ and low TGF-ß in lymphoid organs. The peptide co-localized with F-actin and a nuclear site in dendritic cells and specifically bound to MIF and CD74 in a dot-blot setting. Murine bone-marrow dendritic cells preincubated with Rb9 for 6 h were treated with MIF for short time periods. The modulated responses showed stimulation of CD74 and inhibition of pPI3K, pERK, and pNF-κB as compared to MIF alone. Rb9 in a melanoma-conditioned medium, stimulated the M1 type conversion in bone marrow-macrophages. Functional aspects of Rb9 in vivo were studied in therapeutic and prophylactic protocols using a melanoma metastatic model. In both protocols Rb9 exhibited a marked anti-melanoma protection. Human dendritic cells were also investigated showing increased expression of surface markers in response to Rb9 incubation. Rb9 either stimulated or slightly inhibited moDCs submitted to inhibitory (TGF-ß and IL-10) or activating (LPS) conditions, respectively. Lymphocyte proliferation was obtained with moDCs stimulated by Rb9 and tumor cell lysate. In moDCs from cancer patients Rb9 exerted immunomodulatory activities depending on their functional status. The peptide may inhibit over-stimulated cells, stimulate poorly activated and suppressed cells, or cause instead, little phenotypic and functional alterations. Recently, the interaction MIF-CD74 has been associated to PD-L1 expression and IFN-γ, suggesting a target for melanoma treatment. The effects described for Rb9 and the protection against metastatic melanoma may suggest the possibility of a peptide reagent that could be relevant when associated to modern immunotherapeutic procedures.

Prenatal Androgenization of Ewes as a Model of Hirsutism in Polycystic Ovary Syndrome.

The main clinical feature associated with hyperandrogenism in polycystic ovary syndrome (PCOS) in humans is hirsutism, where hair increases its length, pigmentation, and particularly its diameter. Currently, it is not known whether PCOS animal models also exhibit changes in the hair. Therefore, the aim of this study was to explore the wool characteristics in sheep prenatally androgenized (PA) with testosterone propionate. After 4 and 13 months of life, wool was collected from the top of the shoulder of both females and males (both androgenized and controls). The offspring sheep were followed for up to 19 months of life to evaluate testosterone and androstenedione serum levels by ultra-high-performance liquid chromatography-tandem mass spectrometry, determine insulin and glucose response to intravenous glucose tolerance test, and address estrus cyclicity during the second breeding season. PA male animals showed a reduction in wool fiber diameter at 4 months of age compared with controls (P = 0.02) but not at 13 months, whereas PA females showed increased hair diameter at 13 months (P = 0.002), with no difference at 4 months. No substantial changes in other hair parameters (length, color, and medullation) were identified. In addition, increased levels of serum testosterone were observed in PA female sheep compared with controls at 12 months (P = 0.03). Our results indicate for the first time, to our knowledge, that changes in wool fiber diameter observed in PA ewes replicate, at the translational level, the increase in hair diameter in hirsute women with PCOS.

Identification of di-substituted ureas that prevent growth of trypanosomes through inhibition of translation initiation.

Some 1,3-diarylureas and 1-((1,4-trans)-4-aryloxycyclohexyl)-3-arylureas (cHAUs) activate heme-regulated kinase causing protein synthesis inhibition via phosphorylation of the eukaryotic translation initiation factor 2 (eIF2) in mammalian cancer cells. To evaluate if these agents have potential to inhibit trypanosome multiplication by also affecting the phosphorylation of eIF2 alpha subunit (eIF2α), we tested 25 analogs of 1,3-diarylureas and cHAUs against Trypanosoma cruzi, the agent of Chagas disease. One of them (I-17) presented selectivity close to 10-fold against the insect replicative forms and also inhibited the multiplication of T. cruzi inside mammalian cells with an EC50 of 1-3 µM and a selectivity of 17-fold. I-17 also prevented replication of African trypanosomes (Trypanosoma brucei bloodstream and procyclic forms) at similar doses. It caused changes in the T. cruzi morphology, arrested parasite cell cycle in G1 phase, and promoted phosphorylation of eIF2α with a robust decrease in ribosome association with mRNA. The activity against T. brucei also implicates eIF2α phosphorylation, as replacement of WT-eIF2α with a non-phosphorylatable eIF2α, or knocking down eIF2 protein kinase-3 by RNAi increased resistance to I-17. Therefore, we demonstrate that eIF2α phosphorylation can be engaged to develop trypanosome-static agents in general, and particularly by interfering with activity of eIF2 kinases.

Influência da erosão dentária na adesão de braquetes ortodônticos colados ao esmalte com diferentes materiais / The influence of dental erosion on bond strength of orthodontic brackets bonded to enamel with different materials

O diagnóstico das lesões incipientes de erosão em esmalte é difícil de ser realizado e, em situações clínicas, poderá ocorrer a colagem de braquetes em superfícies erodidas. Este trabalho in vitro avaliou a adesão de braquetes ortodônticos ao esmalte dentário bovino hígido e previamente erodido, utilizando dois materiais para colagem. Os fatores em estudo foram condição prévia do esmalte em 2 níveis (com e sem erosão) e tipo de material de colagem em 2 níveis (Transbond XT e Fuji Ortho LC). A amostra foi composta por 160 coroas de incisivos bovinos, sendo metade dela submetida a desafio erosivo para formação de lesões artificiais de erosão e a outra metade permaneceu hígida. Na ciclagem erosiva as coroas foram imersas 8X/dia em Coca-cola® (10 min), seguido da imersão em saliva artificial (2 h), durante 5 dias. A outra metade da amostra ficou em saliva artificial por 5 dias. Braquetes de incisivo central superior foram colados às coroas hígidas (H) e erodidas (E), seguindo orientações dos fabricantes de cada material. As variáveis de resposta foram resistência ao cisalhamento e índice de remanescente adesivo (IRA). Os dados de resistência ao cisalhamento foram analisados por ANOVA 2 critérios e Teste de Tukey (p<0,05). Os resultados, expressos em megapascal, não mostraram diferenças na resistência ao cisalhamento entre esmalte erodido e hígido, tanto no grupo colado com resina (RH = 15,25 +3,72; RE = 15,79 +4,41) quanto colado com ionômero (IH = 10,70 +3,73; IE = 11,26 +3,70). A resina apresentou resistência à colagem superior ao ionômero. Na comparação do índice de remanescente adesivo, por meio do teste de Mann Whitney, o esmalte erodido apresentou valores mais altos para o IRA, evidenciando uma maior quantidade de material remanescente no esmalte, tanto no grupo colado com resina (p=0,044) quanto com ionômero (p<0,001). Conclui-se que a presença da lesão de erosão não interfere na resistência ao cisalhamento de braquetes colados ao esmalte tanto com resina quanto com cimento de ionômero de vidro. No entanto, independentemente do material de colagem, o índice de remanescente adesivo evidenciou uma maior adesão ao esmalte com erosão.(AU)

The diagnosis of initial erosion lesions on enamel is difficult and in some clinical situations, the professional bonds brackets to eroded surfaces without noting.This in vitro study evaluated the bond strength of orthodontic brackets bonded to eroded and sound bovine enamel with two different materials. The factors under study were enamel condition in two levels (with and without erosion) and type of bonding material in two levels (Transbond® XT and Fuji Ortho LC). The sample consisted of 160 bovine lower incisor teeth, half of the specimens was subjected to erosive challenge to form artificial erosive lesions and the other half remained sound. In the erosive cycling tooth crowns were immerged 8x/day in Coca-cola® (10 min), followed by immersion in artificial saliva for (2 h), for 5 days. The other half of the sample was maintained in artificial saliva for 5 days. At sequence, brackets were bonded to eroded (E) and sound (S) enamel, according to manufacturing recommendations of each material. The response variables were shear bond strength and adhesive remnant index (ARI). Shear bond strength data were analyzed by Two-way ANOVA and Tukeys test (p<0,05). The results, expressed in megapascal, did not show any difference between eroded and sound enamel, in both composite resin (RS = 15,25 +3,72; RE = 15,79 +4,41) and glass ionomer (IS = 10,70 +3,73; IE = 11,26 +3,70) groups. Composite resin showed higher shear bond strength compared to glass ionomer cement. In the comparison of adhesive remnant index using Mann Whitney test, eroded enamel presented higher scores for ARI, showing greater amount of material remaining on enamel, in both resin (p=0,04) and ionomer (p<0,001) groups. It was concluded that the presence of erosion lesions did not interfere on shear bond strength of brackets bonded to enamel with composite resin or glass ionomer cement. However, independently of the bonding material, adhesive remnant index showed higher bond strength to eroded enamel.(AU)

Trypanosoma cruzi P21: a potential novel target for chagasic cardiomyopathy therapy.

Chagas disease, which is caused by the parasite Trypanosoma cruzi, is an important cause of cardiomyopathy in Latin America. It is estimated that 10%-30% of all infected individuals will acquire chronic chagasic cardiomyopathy (CCC). The etiology of CCC is multifactorial and involves parasite genotype, host genetic polymorphisms, immune response, signaling pathways and autoimmune progression. Herein we verified the impact of the recombinant form of P21 (rP21), a secreted T. cruzi protein involved in host cell invasion, on progression of inflammatory process in a polyester sponge-induced inflammation model. Results indicated that rP21 can recruit immune cells induce myeloperoxidase and IL-4 production and decrease blood vessels formation compared to controls in vitro and in vivo. In conclusion, T. cruzi P21 may be a potential target for the development of P21 antagonist compounds to treat chagasic cardiomyopathy.