Unveiling interactions between DNA and cytotoxic 2-arylpiperidinyl-1,4-naphthoquinone derivatives: A combined electrochemical and computational study

Indexación: Scopus.Three 2-arylpiperidinyl-1,4-naphthoquinone derivatives were synthesized and evaluated in vitro to determine their cytotoxicity on cancer and normal cell lines. In order to establish their possible action mechanism, the electrochemical behaviour of these quinones was examined using cyclic voltammetry (CV) as technique by using a three-electrode setup: a glassy carbon, Ag/AgCl (in 3 M KCl), and platinum wire as working, reference, and counter electrodes, respectively. Kinetic studies were done to determine the control of the reduction reaction and the number of transferred electrons in the process. Furthermore, the addition of dsDNA to the quinone solutions allowed for the observation of an interaction between each quinone and dsDNA as the current-peaks became lower in presence of dsDNA. Otherwise, motivated to support the aforementioned results, electronic structure calculations at the TPSS-D3/6-31+G(d,p) level of theory were carried out in order to find the most favourable noncovalently bonded complexes between quinones and DNA. Noncovalent complexes formed between DNA and 2-arylpiperidinyl-1,4-naphthoquinones and stabilized by π-stacking interactions along with the well-known hydrogen-bonded complexes were found, with the former being more stable than the latter. These results suggest that the intercalation of these quinone derivatives in DNA is the most likely action mechanism. © 2018 King Saud Universityhttps://www.sciencedirect.com/science/article/pii/S1878535218300893?via%3Dihu

Ventilatory function in young adults and dietary antioxidant intake

Artículo de publicación ISIDietary antioxidants may protect against poor ventilatory function. We assessed the relation between ventilatory function and antioxidant components of diet in young Chileans. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and the ratio FEV1/FVC were measured in 1232 adults aged 22-28 years, using a Vitalograph device. Dietary intake was ascertained with a food frequency questionnaire (FFQ) designed for this study, from which nutrient and flavonoid intakes were estimated. Dietary patterns were derived with Principal Component Analysis (PCA). After controlling for potential confounders, dietary intake of total catechins was positively associated with FVC (Regression coefficient (RC) of highest vs. lowest quintile of intake 0.07; 95% CI 0.01 to 0.15; p per trend 0.006). Total fruit intake was related to FVC (RC of highest vs. lowest quintile 0.08; 95% CI 0.003 to 0.15; p per trend 0.02). Intake of omega 3 fatty acids was associated with a higher FEV1 (RC for highest vs. lowest quintile 0.08; 95% CI 0.01 to 0.15 L; p per trend 0.02) and with FVC 0.08 (RC in highest vs. lowest quintile of intake 0.08, 95% CI 0.001 to 0.16; p per trend 0.04). Our results show that fresh fruits, flavonoids, and omega 3 fatty acids may contribute to maintain ventilatory function.Wellcome Trust 059448Z

Using a Gridded Global Dataset to Characterize Regional Hydroclimate in Central Chile

Central Chile is facing dramatic projections of climate change, with a consensus for declining precipitation, negatively affecting hydropower generation and irrigated agriculture. Rising from sea level to 6000 m within a distance of 200 km, precipitation characterization is difficult because of a lack of long-term observations, especially at higher elevations. For understanding current mean and extreme conditions and recent hydroclimatological change, as well as to provide a baseline for downscaling climate model projections, a temporally and spatially complete dataset of daily meteorology is essential. The authors use a gridded global daily meteorological dataset at 0.25° resolution for the period 1948–2008, adjusted by monthly precipitation observations interpolated to the same grid using a cokriging method with elevation as a covariate. For validation, daily statistics of the adjusted gridded precipitation are compared to station observations. For further validation, a hydrology model is driven with the gridded 0.25° meteorology and streamflow statistics are compared with observed flow. The high elevation precipitation is validated by comparing the simulated snow extent to Moderate Resolution Imaging Spectroradiometer (MODIS) images. Results show that the daily meteorology with the adjusted precipitation can accurately capture the statistical properties of extreme events as well as the sequence of wet and dry events, with hydrological model results displaying reasonable agreement with observed streamflow and snow extent. This demonstrates the successful use of a global gridded data product in a relatively data-sparse region to capture hydroclimatological characteristics and extremes

Valor predictivo de la procalcitonina en niños con sospecha de sepsis

ResumenIntroducciónEl uso de biomarcadores podría constituir una herramienta en el diagnóstico, pronóstico y estratificación en la sepsis. El objetivo fue analizar el valor de la procalcitonina (PCT), proteína C reactiva (PCR) y lactato en la predicción de shock séptico, mortalidad y en la estratificación en niños con sospecha de sepsis.Pacientes y métodoEstudio prospectivo en 81 pacientes en los cuales se midió niveles plasmáticos de PCT, PCR y lactato al ingreso en la unidad de cuidados intensivos. Los pacientes se categorizaron en síndrome de respuesta inflamatoria sistémica, sepsis, sepsis grave y shock séptico.ResultadosLas concentraciones de la PCT (ng/mL) aumentaron significativamente de acuerdo a la gravedad de la sepsis: 0,36 (0-1,2) para síndrome de respuesta inflamatoria sistémica; 1,96 (0,4-3,5) para sepsis; 7,5 (3,9-11,1) en sepsis grave; y 58,9 (35,1-82,7) para shock séptico (p<0,001). Comparada con la PCR y el lactato, el área bajo la curva ROC reveló un poder discriminativo favorable de la PCT para predecir shock séptico y mortalidad: 0,91 (IC95%: 0,83-0,97) y 0,80 (IC95%: 0,69-0,88), respectivamente.ConclusionesA diferencia de la PCR y el lactato, la determinación de la PCT al ingreso en la unidad de cuidados intensivos es un buen predictor de shock séptico y mortalidad, y permite estratificar a los pacientes de acuerdo a la gravedad de la sepsis.AbstractIntroductionThe use of biomarkers could be a tool for diagnosis, prognosis and stratifying children with sepsis. Our main goal was to analyze the value of procalcitonin (PCT), C reactive protein (CRP) and lactate in predicting mortality, septic shock and the stratification in children with suspected sepsisPatients and methodProspective study in 81 patients. Plasma levels of PCT, CRP and lactate were measured at admission in the pediatric intensive care unit. Patients were categorized into systemic inflammatory response syndrome, sepsis, severe sepsis and septic shock.ResultsConcentrations of PCT (ng/mL) increased significantly according to the severity of sepsis: 0.36 (0-1.2) for systemic inflammatory response syndrome; 1.96 (0.4-3.5) for sepsis; 7.5 (3.9-11.1) for severe sepsis; and 58.9 (35.1-82.7) for septic shock (P<.001). Compared to CRP and lactate, the area under the ROC curve revealed a good discriminative power of PCT to predict septic shock and mortality, 0.91 (95% CI: 0.83-0.97) and 0.80 (95% CI: 0.69-0.88), respectively.ConclusionsIn contrast to CRP and lactate, the determination of PCT in pediatric intensive care unit admission is a good predictor of mortality and septic shock and can stratify patients according to severity of sepsis

Redox-Active Nanomaterials For Nanomedicine Applications

Nanomedicine utilizes the remarkable properties of nanomaterials for the diagnosis, treatment, and prevention of disease. Many of these nanomaterials have been shown to have robust antioxidative properties, potentially functioning as strong scavengers of reactive oxygen species. Conversely, several nanomaterials have also been shown to promote the generation of reactive oxygen species, which may precipitate the onset of oxidative stress, a state that is thought to contribute to the development of a variety of adverse conditions. As such, the impacts of nanomaterials on biological entities are often associated with and influenced by their specific redox properties. In this review, we overview several classes of nanomaterials that have been or projected to be used across a wide range of biomedical applications, with discussion focusing on their unique redox properties. Nanomaterials examined include iron, cerium, and titanium metal oxide nanoparticles, gold, silver, and selenium nanoparticles, and various nanoscale carbon allotropes such as graphene, carbon nanotubes, fullerenes, and their derivatives/variations. Principal topics of discussion include the chemical mechanisms by which the nanomaterials directly interact with biological entities and the biological cascades that are thus indirectly impacted. Selected case studies highlighting the redox properties of nanomaterials and how they affect biological responses are used to exemplify the biologically-relevant redox mechanisms for each of the described nanomaterials