Metal-based compounds containing selenium: An appealing approach towards novel therapeutic drugs with anticancer and antimicrobial effects

In recent years, both metal-based complexes and selenium-containing compounds have been widely explored for their therapeutic properties due to their roles in biological processes and modulation of diverse molecular tar- gets. However, despite their growing interest, there is no review to date that covers the potential use of the combination of these entities to design new therapeutic derivatives. This review highlights the latest achieve- ments in this particular field, with a focus on compounds with anticancer and/or antimicrobial properties. With this aim, the formation of coordination compounds including several metals bearing selenium either with direct interaction with the metal center or as part of the organic ligand elsewhere is covered. Besides, coordination compounds with a Se(IV) center have been assessed. The biological properties of several selenium-containing organometallic complexes have also been discussed, including metallocenes, half-sandwich complexes, and compounds with N-heterocyclic carbenes, CO, and π-ligands, and other σ-bonded entities. The information compiled in this review may be helpful to design and develop novel, more potent, and safer metal-based com- pounds for the treatment of several pathologies

Utilização da Imagem por Ressonância Magnética nos Estudos sobre a Produção da Fala

A fala é uma ferramenta única de comunicação, que envolve um conjunto de órgãos que trabalham sincronamente na produção de sons. Os mecanismos envolvidos são complexos, sendo várias as técnicas de estudo da fala, quer do ponto de vista acústico, quer do ponto de vista morfológico. A ressonância magnética tem revelado potencialidades únicas no estudo do tracto vocal, e que são aqui destacadas. O principal objectivo deste estudo é dar a conhecer esta técnica de imagem e demonstrar a sua utilização no estudo da produção da fala, nomeadamente do Português Europeu. Através da recolha e análise de imagens foi possível a obtenção e construção de modelos tridimensionais do tracto vocal nas mais variadas posições articulatórias. Recorrendo a uma técnica de sincronização através de monitorização cardíaca e a aquisições de imagem ultra-rápidas foi possível também a captação dinâmica por sub-amostragem e a observação dos movimentos articulatórios envolvidos durante a produção de três sílabas. A caracterização morfológica e dinâmica do tracto vocal com base nas imagens de ressonância magnética é, face aos resultados obtidos, fiável e deveras importante para o conhecimento deste mecanismo. Para além disso, a informação obtida desperta um interesse multidisciplinar e aplicações diversas com potencialidades marcantes face aos esperados avanços tecnológicos desta técnica de imagem

Morfometria do trato vocal por ressonância magnética: simulação de padrões patológicos articulatórios

Introdução - A análise da forma ou morfometria de estruturas anatómicas, como o trato vocal, pode ser efetuada a partir de imagens bidimensionais (2D) como de aquisições volumétricas (3D) de ressonância magnética (RM). Esta técnica de imagem tem vindo a ter uma utilização crescente no estudo da produção da fala. Objetivos - Demonstrar como pode ser efetuada a morfometria do trato vocal a partir da imagem por ressonância magnética e ainda apresentar padrões anatómicos normais durante a produção das vogais [i a u] e dois padrões articulatórios patológicos em contexto simulado. Métodos - As imagens consideradas foram recolhidas a partir de aquisições 2D (Turbo Spin-eco) e 3D (Flash Gradiente-Eco) de RM em quatro sujeitos durante a produção das vogais em estudo; adicionalmente procedeu-se à avaliação de duas perturbações articulatórias usando o mesmo protocolo de RM. A morfometria do trato vocal foi extraída com recurso a técnicas manuais (para extração de cinco medidas articulatórias) e automáticas (para determinação de volumes) de processamento e análise de imagem. Resultados - Foi possível analisar todo o trato vocal, incluindo a posição e a forma dos articuladores, tendo por base cinco medidas descritivas do posicionamento destes órgãos durante a produção das vogais. A determinação destas medições permitiu identificar quais as estratégias mais comummente adotadas na produção de cada som, nomeadamente a postura articulatória e a variação de cada medida para cada um dos sujeitos em estudo. No contexto de voz falada intersujeitos, foi notória a variabilidade nos volumes estimados do trato vocal para cada som e, em especial, o aumento do volume do trato vocal na perturbação articulatória de sigmatismo. Conclusão - A imagem por RM é, sem dúvida, uma técnica promissora no estudo da fala, inócua, não-invasiva e que fornece informação fiável da morfometria do trato vocal.Introduction - The shape or morphologic analysis of anatomical structures, such as the vocal tract can be performed from two-dimensional (2D) or volumetric acquisitions (3D) of magnetic resonance imaging (MRI). This imaging technique has had an increasing use in the study of speech production. Objectives - To determine a method to perform the morphometric analysis of the vocal tract from magnetic resonance imaging; to present anatomical patterns during the normal speech production of some vowels and two pathological articulatory disorders in simulated context. Methods - The image data was collected from 2D (Turbo Spin Echo) and 3D (Flash Gradient Echo) acquisitions of MRI of four subjects during the production of three vowels; in addition, two articulatory disorders were assessed using this imaging protocol. The morphology of the vocal tract was extracted using manual and automatic techniques of image processing and analysis. Results - Based on five articulatory measurements, it was possible to study the entire vocal tract during vowel production, including the position and shape of the articulators involved. Based on these measurements, it was possible to identify the strategies most commonly adopted in the production of each sound, including the articulatory posture and the modification of each measure for the subjects under study. Concerning the voices of the different speakers, the variability in the assessed volumes of the vocal tract for each sound was found, and in particular, the increased vocal tract volume in the articulatory disorder - the sigmatism. Conclusion - MRI is a promising technique for speech production studies, safe, non-invasive and that provides reliable information concerning the morphometric analysis of the vocal tract

Transcriptome analysis of flathead grey mullet (Mugil cephalus) ovarian development induced by recombinant gonadotropin hormones

Background: Treatment with recombinant gonadotropin hormones (rGths), follicle-stimulating hormone (rFsh) and luteinizing hormone (rLh), was shown to induce and complete vitellogenesis to finally obtain viable eggs and larvae in the flathead grey mullet (Mugil cephalus), a teleost arrested at early stages of gametogenesis in intensive captivity conditions. This study aimed to investigate the transcriptomic changes that occur in the ovary of females during the rGths-induced vitellogenesis. Methods: Ovarian samples were collected through biopsies from the same five females at four stages of ovarian development. RNASeq libraries were constructed for all stages studied, sequenced on an Illumina HiSeq4000, and a de novo transcriptome was constructed. Differentially expressed genes (DEGs) were identified between stages and the functional properties of DEGs were characterized by comparison with the gene ontology and Kyoto Encyclopedia. An enrichment analysis of molecular pathways was performed. Results: The de novo transcriptome comprised 287,089 transcripts after filtering. As vitellogenesis progressed, more genes were significantly upregulated than downregulated. The rFsh application induced ovarian development from previtellogenesis to early-to-mid-vitellogenesis with associated pathways enriched from upregulated DEGs related to ovarian steroidogenesis and reproductive development, cholesterol metabolism, ovarian growth and differentiation, lipid accumulation, and cell-to-cell adhesion pathways. The application of rFsh and rLh at early-to-mid-vitellogenesis induced the growth of oocytes to late-vitellogenesis and, with it, the enrichment of pathways from upregulated DEGs related to the production of energy, such as the lysosomes activity. The application of rLh at late-vitellogenesis induced the completion of vitellogenesis with the enrichment of pathways linked with the switch from vitellogenesis to oocyte maturation. Conclusion: The DEGs and enriched molecular pathways described during the induced vitellogenesis of flathead grey mullet with rGths were typical of natural oogenesis reported for other fish species. Present results add new knowledge to the rGths action to further raise the possibility of using rGths in species that present similar reproductive disorders in aquaculture, the aquarium industry as well as the conservation of endangered species.info:eu-repo/semantics/publishedVersio

Design, synthesis and anticancer evaluation of novel Se-NSAID hybrid molecules: Identification of a Se-indomethacin analog as a potential therapeutic for breast cancer

A total of twenty-five novel carboxylic acid, methylester, methylamide or cyano nonsteroidal anti-inflammatory drug (NSAID) derivatives incorporating Se in the chemical form of selenoester were reported. Twenty Se-NSAID analogs exhibited an increase in cytotoxic potency compared with parent NSAID scaffolds (aspirin, salicylic acid, naproxen, indomethacin and ketoprofen). Top five analogs were selected to further study their cytotoxicity in a larger panel of cancer cells and were also submitted to the DTP program of the NCI’s panel of 60 cancer cell lines. Compounds 4a and 4d stood out with IC50 values below 10 μM in several cancer cells along with a selectivity index higher than 5 in breast cancer cells. Remarkably, analog 4d was found to inhibit cell growth notably in two breast cancer cell lines by inducing apoptosis, and to be metabolized to release the parent NSAID along with the Se fragment. Taken together, our results show that Se-NSAID analog 4d could be a potential chemotherapeutic drug for breast cancer

Novel N,N' -Disubstituted Acylselenoureas as Potential Antioxidant and Cytotoxic Agents

Selenium compounds are pivotal in medicinal chemistry for their antitumoral and antioxidant properties. Forty seven acylselenoureas have been designed and synthesized following a fragment-based approach. Different scaffolds, including carbo- and hetero-cycles, along with mono- and bi-cyclic moieties, have been linked to the selenium containing skeleton. The doseand time-dependent radical scavenging activity for all of the compounds were assessed using the in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,20 -azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assays. Some of them showed a greater radical scavenging capacity at low doses and shorter times than ascorbic acid. Therefore, four compounds were evaluated to test their protective effects against H2O2-induced oxidative stress. One derivative protected cells against H2O2-induced damage, increasing cell survival by up to 3.6-fold. Additionally, in vitro cytotoxic activity of all compounds was screened against several cancer cells. Eight compounds were selected to determine their half maximal inhibitory concentration (IC50) values towards breast and lung cancer cells, along with their selectivity indexes. The breast cancer cells turned out to be much more sensitive than the lung. Two compounds (5d and 10a) stood out with IC50 values between 4.2 µM and 8.0 µM towards MCF-7 and T47D cells, with selectivity indexes greater than 22.9. In addition, compound 10b exhibited dual antioxidant and cytotoxic activities. Although further evidence is needed, the acylselenourea scaffold could be a feasible frame to develop new dual agents

Three-dimensional visualization of teeth by magnetic resonance imaging during speech

Teeth morphology and oral cavity visualization through imaging techniques enables an accurate vocal tract assessment in speech research, especially when by Magnetic Resonance Imaging (MRI)info:eu-repo/semantics/publishedVersio

Vocal tract morphometry by magnetic resonance imaging: simulation of pathological articulatory patterns

Introduction – The shape or morphologic analysis of anatomical structures, such as the vocal tract can be performed from two-dimensional (2D) or volumetric acquisitions (3D) of magnetic resonance imaging (MRI). This imaging technique has had an increasing use in the study of speech production. Objectives – To determine a method to perform the morphometric analysis of the vocal tract from magnetic resonance imaging; to present anatomical patterns during the normal speech production of some vowels and two pathological articulatory disorders in simulated context. Methods – The image data was collected from 2D (Turbo Spin Echo) and 3D (Flash Gradient Echo) acquisitions of MRI of four subjects during the production of three vowels; in addition, two articulatory disorders were assessed using this imaging protocol. The morphology of the vocal tract was extracted using manual and automatic techniques of image processing and analysis. Results – Based on five articulatory measurements, it was possible to study the entire vocal tract during vowel production, including the position and shape of the articulators involved. Based on these measurements, it was possible to identify the strategies most commonly adopted in the production of each sound, including the articulatory posture and the modification of each measure for the subjects under study. Concerning the voices of the different speakers, the variability in the assessed volumes of the vocal tract for each sound was found, and in particular, the increased vocal tract volume in the articulatory disorder – the sigmatism. Conclusion – MRI is a promising technique for speech production studies, safe, non-invasive and that provides reliable information concerning the morphometric analysis of the vocal tract