Effect of DNA repair deficiencies on the cytotoxicity of resveratrol

Numerous preclinical studies have shown that the naturally-occurring polyphenol resveratrol may produce health-beneficial effects in a variety of disorders, including cancer, diabetes, Alzheimer, and cardiovascular diseases. Resveratrol has entered clinical trials for the prevention and treatment of several of these disorders. This polyphenol is also available in the market as a dietary supplement. Experimental data have shown, however, that resveratrol induces DNA damage in a variety of cells. Here we review such evidence and evaluate the cytotoxicity of resveratrol (MTT assay) in cells deficient in several major DNA repair pathways (i.e., homologous recombination, non-homologous end joining, base excision repair, nucleotide excision repair, mismatch repair, and Fanconi anemia repair). Cells deficient in base excision repair (EM9), nucleotide excision repair (UV4 and UV5) and Fanconi Anemia (KO40) were slightly hypersensitive to resveratrol-induced cytotoxicity with respect to their parental cells (AA8). Our results suggest that these pathways may participate in the repair of the DNA damage induced by resveratrol and that deficiencies in these pathways may confer hypersensitivity to the genotoxic activity of this dietary constituen

Universality of cauliflower-like fronts: from nanoscale thin films to macroscopic plants

Chemical vapor deposition (CVD) is a widely used technique to grow solid materials with accurate control of layer thickness and composition. Under mass-transport-limited conditions, the surface of thin films thus produced grows in an unstable fashion, developing a typical motif that resembles the familiar surface of a cauliflower plant. Through experiments on CVD production of amorphous hydrogenated carbon films leading to cauliflower-like fronts, we provide a quantitative assessment of a continuum description of CVD interface growth. As a result, we identify non-locality, non-conservation and randomness as the main general mechanisms controlling the formation of these ubiquitous shapes.We also show that the surfaces of actual cauliflower plants and combustion fronts obey the same scaling laws, proving the validity of the theory over seven orders of magnitude in length scales. Thus, a theoretical justification is provided, which had remained elusive so far, for the remarkable similarity between the textures of surfaces found for systems that differ widely in physical nature and typical scales.Publicad

Implementación de un algoritmo de filtrado en microcontroladores dsPICy PIC32

Se implementa un algoritmo para la Trasformada Rápida de Fourier (FFT) en microcontroladores dsPIC y PIC32 mediante la reutilización software, lo cual permite disminuir el esfuerzo y el tiempo en programación. Los conocimientos necesarios para su implementación son mínimos por parte del programador, utilizándose librerías de funciones matemáticas y números complejos. Se busca generalizar el uso de los algoritmos de filtrado con los dispositivos genéricos utilizados. Se observa que la implementación de Filtros Lineales de Respuesta Finita (FIR) requiere menos cálculo computacional que la FFT. También se observa que existe una limitación en la longitud del vector donde se alojan los valores digitales provenientes de la operación de conversión analógica a digital. Para el caso de los PIC 32 esta longitud es de 512 y para los dsPIC es de 128. Es posible aumentar este número cambiando las condiciones de compilación y linkeo del simulador MPLAB. Los resultados obtenidos del hardware se pueden extender a otros desarrollos genéricos que utilicen dsPIC y PIC32.Sociedad Argentina de Informática e Investigación Operativa (SADIO

Implementación de un algoritmo de filtrado en microcontroladores dsPICy PIC32

Se implementa un algoritmo para la Trasformada Rápida de Fourier (FFT) en microcontroladores dsPIC y PIC32 mediante la reutilización software, lo cual permite disminuir el esfuerzo y el tiempo en programación. Los conocimientos necesarios para su implementación son mínimos por parte del programador, utilizándose librerías de funciones matemáticas y números complejos. Se busca generalizar el uso de los algoritmos de filtrado con los dispositivos genéricos utilizados. Se observa que la implementación de Filtros Lineales de Respuesta Finita (FIR) requiere menos cálculo computacional que la FFT. También se observa que existe una limitación en la longitud del vector donde se alojan los valores digitales provenientes de la operación de conversión analógica a digital. Para el caso de los PIC 32 esta longitud es de 512 y para los dsPIC es de 128. Es posible aumentar este número cambiando las condiciones de compilación y linkeo del simulador MPLAB. Los resultados obtenidos del hardware se pueden extender a otros desarrollos genéricos que utilicen dsPIC y PIC32.Sociedad Argentina de Informática e Investigación Operativa (SADIO

A hydroalcoholic extract from the leaves of Nerium oleander inhibits glycolysis and induces selective killing of lung cancer cells

Recent evidence suggests that cardiac glycosides might be used for the treatment of cancer. The ornamental shrub Nerium oleander has been used in traditional medicine for treating several disorders including cancer, and extracts from the leaves of this plant have already entered phase I clinical trials. In this communication, we have prepared a hydroalcoholic extract from the leaves of Nerium oleander (containing 4.75 ± 0.32 % of cardenolides) and have assessed its cytotoxic activity in A549 lung cancer cells vs. MRC5 nonmalignant lung fibroblasts. The results showed that the cytotoxicity of the Nerium oleander extract against the cancer cell line was significantly higher than that against the nonmalignant cell line, with a potency and selectivity similar to those of the anticancer drug cisplatin. Pretreatment of A549 cells with the antioxidants N-acetylcysteine and catalase slightly prevented the cytotoxicity of the extract, therefore suggesting that the formation of reactive oxygen species participates in its cytotoxic activity but does not play a major role. Nerium oleander extract-induced cytotoxicity and DNA damage (gamma-H2AX focus formation) were slightly higher in cells lacking BRCA2 (deficient in homologous recombination repair) than in parental cells; this indicates that the induction of DNA damage may also play a role in the cytotoxicity of the extract. Nerium oleander extract induced a marked inhibition of glycolysis (glucose consumption and lactate production) in A549 cells, comparable to that of the glycolysis inhibitor dichloroacetate (currently in clinical development for cancer therapy). Because platinum compounds are widely used in the treatment of lung cancer, we tested the cytotoxicity of several combinations of cisplatin with the extract and found a moderate synergism when Nerium oleander extract was administered after cisplatin but a moderate antagonism when it was added before cisplatin. Our results suggest that extracts from Nerium oleander might induce anticancer effects in patients with lung cancer and support their possible advancement into phase II clinical trials for the treatment of this type of cancer

Special issue on surfaces patterned by ion sputtering

We thank all the authors within this issue for their efforts and contributions, and the editorial staff of Journal of Physics: Condensed Matter for their efficient work. We also acknowledge funding by the MINECO/FEDER (Spain/ UE) grant Nos. MAT2017-85089-C2-1-R, MAT2016-80394-R, FIS2015-66020-C2-1-P, FIS2015-73337-JIN, FIS2016-78883-C2-2-P, BIO2016-79618-R, and CTQ2017-84309-C2-2-R, and by Comunidad de Madrid grant NANOAVANSENS ref. S2013/MIT-3029. ARC acknowledges the Ramón y Cajal contract number RYC-2015-18047

Brain complications from odontogenic infections: A systematic review

Purpose: Odontogenic infections can spread through different routes to more remote anatomical areas, such as the brain. Brain abscesses have an incidence of 0.3−1.3 / 100,000 population and only 2−5% are of dental origin. The main objective is to research brain complications derived from odontogenic infections. Secondary objectives were to identify the most common symptoms in brain abscess, to describe the microbiology involved in these infectious processes, report which parts of the brain complex are most commonly affected and report the sequelae of this patients. Methods: A systematic review following the PRISMA Guide and the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports was carried out in PubMed, Scopus and Web of Science. The search terms were: Brain infection, brain abscess, oral health oral origin, odont* infect*. Results: The database search identified a total of 1000 articles. A total of 18 publications were identified after applying inclusion and exclusion criteria. A total of 38 patients were analyzed. Mean age was 49.64§ 18.80 years. Conclusion: The most common symptoms of patients with brain abscess are neurological affectations first and then fever and headache second, without necessarily presenting as a symptomatological triad. Microbiological diagnosis is key to determining the origin of the infection. Anaerobic pathogens such as Streptococcus (F. Milleri), Fusobacterium Nucleatum and Porfiromonas Gingivalis families are common bacterial agents. The frontal lobe is the most frequently affected, followed by the parietal and temporal lobe. The most frequent brain complications are neurological disorders. However, most patients with brain abscesses recover without sequelae

Cells Deficient in the Fanconi Anemia Protein FANCD2 are Hypersensitive to the Cytotoxicity and DNA Damage Induced by Coffee and Caffeic Acid

Epidemiological studies have found a positive association between coffee consumption and a lower risk of cardiovascular disorders, some cancers, diabetes, Parkinson and Alzheimer disease. Coffee consumption, however, has also been linked to an increased risk of developing some types of cancer, including bladder cancer in adults and leukemia in children of mothers who drink coffee during pregnancy. Since cancer is driven by the accumulation of DNA alterations, the ability of the coffee constituent caffeic acid to induce DNA damage in cells may play a role in the carcinogenic potential of this beverage. This carcinogenic potential may be exacerbated in cells with DNA repair defects. People with the genetic disease Fanconi Anemia have DNA repair deficiencies and are predisposed to several cancers, particularly acute myeloid leukemia. Defects in the DNA repair protein Fanconi Anemia D2 (FANCD2) also play an important role in the development of a variety of cancers (e.g., bladder cancer) in people without this genetic disease. This communication shows that cells deficient in FANCD2 are hypersensitive to the cytotoxicity (clonogenic assay) and DNA damage (γ-H2AX and 53BP1 focus assay) induced by caffeic acid and by a commercial lyophilized coffee extract. These data suggest that people with Fanconi Anemia, or healthy people who develop sporadic mutations in FANCD2, may be hypersensitive to the carcinogenic activity of coffee

Evaluating the cancer therapeutic potential of cardiac glycosides

Cardiac glycosides, also known as cardiotonic steroids, are a group of natural products that share a steroid-like structure with an unsaturated lactone ring and the ability to induce cardiotonic effects mediated by a selective inhibition of the Na(+)/K(+)-ATPase. Cardiac glycosides have been used for many years in the treatment of cardiac congestion and some types of cardiac arrhythmias. Recent data suggest that cardiac glycosides may also be useful in the treatment of cancer. These compounds typically inhibit cancer cell proliferation at nanomolar concentrations, and recent high-throughput screenings of drug libraries have therefore identified cardiac glycosides as potent inhibitors of cancer cell growth. Cardiac glycosides can also block tumor growth in rodent models, which further supports the idea that they have potential for cancer therapy. Evidence also suggests, however, that cardiac glycosides may not inhibit cancer cell proliferation selectively and the potent inhibition of tumor growth induced by cardiac glycosides in mice xenografted with human cancer cells is probably an experimental artifact caused by their ability to selectively kill human cells versus rodent cells. This paper reviews such evidence and discusses experimental approaches that could be used to reveal the cancer therapeutic potential of cardiac glycosides in preclinical studie

Concurrent segregation and erosion effects in medium-energy iron beam patterning of silicon surfaces

This paper is part of: Special Issue on Surfaces Patterned by Ion SputteringWe have bombarded crystalline silicon targets with a 40 keV Fe+ ion beam at different incidence angles. The resulting surfaces have been characterized by atomic force, current-sensing and magnetic force microscopies, scanning electron microscopy, and x-ray photoelectron spectroscopy. We have found that there is a threshold angle smaller than 40 degrees for the formation of ripple patterns, which is definitely lower than those frequently reported for noble gas ion beams. We compare our observations with estimates of the value of the critical angle and of additional basic properties of the patterning process, which are based on a continuum model whose parameters are obtained from binary collision simulations. We have further studied experimentally the ripple structures and measured how the surface slopes change with the ion incidence angle. We explore in particular detail the fluence dependence of the pattern for an incidence angle value (40 degrees) close to the threshold. Initially, rimmed holes appear randomly scattered on the surface, which evolve into large, bug-like structures. Further increasing the ion fluence induces a smooth, rippled background morphology. By means of microscopy techniques, a correlation between the morphology of these structures and their metal content can be unambiguously established.This research is supported by the MINECO/FEDER (Spain/UE) grants Nos. MAT2017-85089-C2-1-R, MAT2016-80394-R, FIS2015-66020-C2-1-P, FIS2015-73337-JIN, FIS2016-78883-C2-2-P, and BIO2016-79618-R, and by Comunidad de Madrid grant NANOAVANSENS ref. S2013/MIT-3029. We want to thank C. Ballesteros and B. Galiana for their help in the SEM measurements. ARC acknowledges the Ramón y Cajal contract number RYC-2015-18047 and KL thanks FCT, Portugal, for her grant as Investigador FCT