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Acute myeloid leukaemia (AML) is a haematological malignancy characterised by the accumulation of transformed myeloid progenitors in the bone marrow. Piplartine (PL), also known as piperlongumine, is a pro-oxidant small molecule extracted from peppers that has demonstrated antineoplastic potential in solid tumours and other haematological malignancies. In this work, we explored the potential of PL to treat AML through the use of a combination of cellular and molecular analyses of primary and cultured leukaemia cells in vitro and in vivo. We showed that PL exhibits in vitro cytotoxicity against AML cells, including CD34+ leukaemia-propagating cells, but not healthy haematopoietic progenitors, suggesting anti-leukaemia selectivity. Mechanistically, PL treatment increased reactive oxygen species (ROS) levels and induced ROS-mediated apoptosis in AML cells, which could be prevented by treatment with the antioxidant scavenger N-acetyl-cysteine and the pancaspase inhibitor Z-VAD(OMe)-FMK. PL treatment reduced NFKB1 gene transcription and the level of NF-κB p65 (pS536), which was depleted from the nucleus of AML cells, indicating suppression of NF-κB p65 signalling. Significantly, PL suppressed AML development in a mouse xenograft model, and its combination with current AML treatments (cytarabine, daunorubicin and azacytidine) had synergistic effects, indicating translational therapeutic potential. Taken together, these data position PL as a novel anti-AML candidate drug that can target leukaemia stem/progenitors and is amenable to combinatorial therapeutic strategies.

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The guava (Psidium guajava L.) is a climacteric fruit with an accelerated post-harvest overripening. miRNAs are small RNA sequences that function as gene regulators in eukaryotes and are essential for their survival and development. In this study, miRNA libraries were constructed, sequenced and analyzed from the breaker and ripe stages of guava fruit cv. Siglo XXI. One hundred and seventy-four mature miRNA sequences from 28 miRNA families were identified. The taxonomic distribution of the guava miRNAs showed a high level of conservation among the dicotyledonous plants. Most of the predicted miRNA target genes were transcription factors and genes involved in the metabolism of phytohormones such as abscisic acid, auxins, and ethylene, as revealed through an ontology enrichment analysis. The miRNA families miR168, miR169, miR396, miR397, and miR482 were classified as being directly associated with maturation, whereas the miRNA families miR160, miR165, miR167, miR3930, miR395, miR398, and miR535 were classified as being indirectly associated. With this study, we intended to increase our knowledge and understanding of the regulatory process involved in the ripening process, thereby providing valuable information for future research on the ripening of guava fruit.

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Mammillaria bombycina is a cactus distributed in the central region of Mexico. Cactaceae have the particularity of surviving drought and high temperatures, which is why in vitro propagation studies have been carried out successfully to preserve this species and use it as a study model in cacti. In this contribution, a de novo transcriptome of M. bombycina was produced under in vitro conditions for the identification and expression of genes related to abiotic stress. Samples were sequenced using an Illumina platform, averaging 24 million clean readings. From assembly and annotation, 84,975 transcripts were generated, 55% of which were unigenes. Among these, the presence of 13 isoforms of genes belonging to glyoxalase I, II and III were identified. An analysis of the qRT-PCR expression of these genes was performed under in vitro and ex vitro conditions and dehydration at 6 and 24 h. The highest expression was observed under greenhouse conditions and dehydration at 24 h, according to the control. The de novo assembly of the M. bombycina transcriptome remains a study model for future work in cacti.

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A clear understanding of the dependence of mechanical properties of bone remains a task not fully achieved. In order to estimate the mechanical properties in bones for implants, pore cross-section area, calcium content, and apparent density were measured in trabecular bone samples for human implants. Samples of fresh and defatted bone tissue, extracted from one year old bovines, were cut in longitudinal and transversal orientation of the trabeculae. Pore cross-section area was measured with an image analyzer. Compression tests were conducted into rectangular prisms. Elastic modulus presents a linear tendency as a function of pore cross-section area, calcium content and apparent density regardless of the trabecular orientation. The best variable to estimate elastic modulus of trabecular bone for implants was pore cross-section area, and affirmations to consider Nukbone process appropriated for marrow extraction in trabecular bone for implantation purposes are proposed, according to bone mechanical properties. Considering stress-strain curves, defatted bone is stiffer than fresh bone. Number of pores against pore cross-section area present an exponential decay, consistent for all the samples. These graphs also are useful to predict elastic properties of trabecular samples of young bovines for implants.

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The significance of microorganisms in root canals with regard to the aetiology of periapical infection and the need for crucial bacteria control during treatment are undeniable. In this study, we report and discuss a review of the literature on Microbiological Root Canal Sampling (MRS). The procedure is analyzed in detail, discussing its powers, limitations and the influence of sample collection procedures on the incidence of true and false positive results. Data sources: MEDLINE/PUBMED, B-On and library files of Oporto University were accessed. Selection: Papers were selected using the keywords: “root ca¬nal sampling”; “apical periodontitis”; “endodontic pathogens”; “root canal infection”; “Culture”; “molecular biology”. The references were selected under inclusion criteria such as English language, accessibility, relevance to the theme and scientific rigor. Conclusions: This review illustrated the absolute need to adhere to strict methodology procedures if valid samples are to be obtained. A combination of Culture and molecular identification approaches have confirmed the polymicrobial nature of endodontic infections with a predominance of anaerobic bacteria. Nucleic acid-based techniques provide significant additional information particularly regarding the not-yet-cultivable species of the microbial community, but greatly increase the budget of the procedure. Thus, assessment of the endodontic microflora, in the context of a polymicrobial biofilm ecosystem, and its relevance to endodontic treatments must rely in the complementariness of Culture and Metagenomics approaches as they are neither mutually exclusive nor competitive, but strongly complementary...

A importância de microrganismos em canais radiculares no que diz respeito à etiologia da infecção periapical e a necessidade de controlar bactérias durante o tratamento são incontestáveis. Neste estudo, relata-se e discute-se uma revisão da literatura sobre a amostragem microbiológica de canal radicular. O procedimento é analisado em detalhes, discutindo suas atribuições, limitações e influência de procedimentos de coleta de amostra sobre a incidência de verdadeiros e falsos resultados positivos. Fontes de dados: Foram usados MEDLINE/PubMed, B-On e arquivos da biblioteca da Universidade do Porto. Seleção: Os trabalhos foram selecionados utilizando as palavras-chave: “root canal sampling”; “apical periodontitis”; “endodontic pathogens”; “root canal infection”; “Culture”; “molecular biology”. As referências foram selecionadas de acordo com critérios de inclusão como o idioma inglês, acessibilidade, relevância para o tema e rigor científico. Conclusões: Esta revisão ilustrou a absoluta necessidade de aderir aos procedimentos metodológicos rigorosos se se pretende obter amostras válidas para análise. Uma combinação de cultura e abordagens de iden¬tificação molecular confirmaram a natureza polimicrobiana das infeções endodônticas com predominância de bactérias anaeróbias. Técnicas baseadas em ácidos nucleicos fornecem informação adicional significativa, particularmente em relação às espécies não cultiváveis da comunidade microbiana, mas aumentam muito o orçamento do procedimento. Assim, a avaliação da microflora endodôntica, no contexto de um ecossistema polimicrobiano em biofilme, e sua relevância para tratamentos endodônticos devem confiar na complementaridade entre a abordagem de cultura e de metagenômica, pois não são mutuamente exclusivas nem competitivas, mas fortemente complementares...

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Small angle X-ray scattering (SAXS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) have been used to look at enamel from nine premolars, three each from individuals in low, medium and high risk caries groups. Only SAXS was able to detect consistent differences between any of the groups. In enamel from the high caries risk group, the micropores between the hydroxyapatite crystals were laminar. In enamel from the low caries risk group, the micropores were cylindrical. Other parameters varied between teeth but were not correlated with caries risk.

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En la práctica de la angioplastía coronaria transluminal percutánea (ACTP), los problemas más importantes por resolver son la disección aguda, los resultados insatisfactorios y fundamentalmente el desarrollo de reestenosis; uno de los enfoques para resolver estas complicaciones ha sido el desarrollo de férulas endovasculares universalmente conocidas como stents (S). Esta tecnología es costosa para nuestro país, lo que estimuló el diseño y construcción de un S denominado SAQ que es motivo del estudio. Se presenta: La Metodología del desarrollo, fabricación y resultados in vitro y en vivo del SAQ; los resultados ex vivo, obtenidos en arterias coronarias de cerdo y en corazón humano; los resultados de dos modelos en animales: aorta de conejo y arterias periféricas en perro. En este trabajo se demuestra que el SAQ es seguro y efectivo, con propiedades generales semejantes a los existentes en el mercado

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Para confirmar la hipótesis de que la hidrodinámica de los aneurismas cerebrales depende en parte de la posición de éstos, respecto a la fuerza de la gravedad, se desarrolló un modelo experimental de aneurisma en látex, sometido a flujo pulsátil. Con inyección de tintes y radioisótopos, se hicieron registros en 4 posiciones diferentes. Se diseñó un modelo físico que permitió el análisis cuantitativo de los resultados y que abre además la posibilidad de analizar matemáticamente la hidrodinámica de los aneurismas. Los resultados sugieren que cuando el aneurisma se encuentra orientado en contra de la fuerza de gravedad, tiene muy bajo riesgo de trombosis y la escasa turbulencia de su flujo condiciona un menor riesgo de crecimiento y ruptura respecto a cualquier otra posición. La mayor turbulencia en el flujo de la pared la tiene el aneurisma orientado hacia abajo, es decir, paralelo a la fuerza de gravedad. El aneurisma orientado hacia abajo es el que por su hidrodinámica, tiene más posibilidades de complicarse, ya que se tiene: a) un mayor riesgo de ruptura debido al impacto del chorro sobre la pared y la turbulencia que este impacto produce, b) un mayor riesgo de trombosis producida por la éstasis circulatoria que tiene en su cúpula. Esta combinación de factores (ruptura y trombosis) hace que estos aneurismas tiendan a crecer más que otros

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