Modulation of the UV-B-induced Oxidative Stress and Apoptosis in HaCaT Cell Line with Calluna vulgaris Extract

The reactive oxygen species (ROS) production due to ultraviolet B (UV-B) exposure is extremely harmful to the skin. It causes lesions of DNA, proteins and lipids and leads to cellular death. In the present study the UV-B-induced ROS and subsequent apoptosis in the human keratinocyte cell line (HaCaT) were counterbalanced by a plant extract with antioxidant capacity. Some molecules modulated by common heather (Calluna vulgaris) (CV) extract through which this may exert its photoprotective effects were also identified. The ROS were evaluated with CM-H2DCFDA assay, while apoptosis and Bax-α/Bcl-xL molecules with ELISA. The extract was standardized according to its polyphenolic content and the most important biologically active compounds, such as hyperozid, quercetin, isoquercetin, kampferol were evidenced by high-performance liquid chromatography. The UV-B induced ROS production occurred at its highest level at 2 h after the exposure of the HaCaT cells, while apoptosis later, at 4 h. The most significant changes in Bax-α and Bcl-XL proteins induced by UV-B, as well as the highest effect of the extract on apoptosis, were both registered at 4 h. The CV extract decreased concentration- and time-dependently the UV-B-induced ROS production and prevented apoptosis. These effects of CV occurred, at least to a certain extent, due to the modulation of Bax-α/Bcl-XL proteins. These findings suggest that skin cells could be protected from some of the UV-B-induced harmful effects by the administration of the CV extract, which may be further exploited as a potential photoprotective agent

Dynamics of ozone and nitrogen oxides at Summit, Greenland: I. Multi-year observations in the snowpack

© 2015 Elsevier Ltd. A multi-year investigation of ozone (O3) and nitrogen oxides (NOx) in snowpack interstitial air down to a depth of 2.8 m was conducted at Summit, Greenland, to elucidate mechanisms controlling the production and destruction of these important trace gases within the snow. Snowpack O3 values ranged from 30 to 40 ppbv during winter months, and dropped below 10 ppbv in summer. Wintertime NOx levels were low at all depths in the snowpack (below 10 pptv for NO and below 25 pptv for NO2). In the summer, NO values up to 120 pptv, and NO2 mixing ratios up to ∼700 pptv were observed. O3 loss within the snowpack was observed throughout all seasons. The magnitude of the O3 loss rate tracked the seasonal and diurnal cycle of incoming short wave solar radiation. Production of NO within a shallow layer of the snowpack was recorded during the spring and summer months. NO2 production also occurred, and heightened levels were measured down to 2.5 m in the snowpack. The average daily maximum in NO was observed at solar noon, and the minimum was seen during night. The daily peak in NO2 was on average 7 h shifted from the incoming solar radiation and NO maxima. NOx levels in interstitial air during spring were enhanced relative to summer and fall. The influence of meteorological effects such as wind pumping on snowpack interstitial air levels of O3 and NOx was investigated using case study periods. Increased snowpack ventilation during high wind events was found to yield enhancement in snowpack NOx, with this effect being enhanced during times when O3 was elevated in ambient air. This behavior suggests that O3 is involved in NOx production in the snowpack. This extensive set of observations is used to re-evaluate physical and chemical processes that describe the dynamic O3 and NOx chemistry occurring within snowpack interstitial air at Summit

Rare coding variation provides insight into the genetic architecture and phenotypic context of autism

International audienceSome individuals with autism spectrum disorder (ASD) carry functional mutations rarely observed in the general population. We explored the genes disrupted by these variants from joint analysis of protein-truncating variants (PTVs), missense variants and copy number variants (CNVs) in a cohort of 63,237 individuals. We discovered 72 genes associated with ASD at false discovery rate (FDR) ≤ 0.001 (185 at FDR ≤ 0.05). De novo PTVs, damaging missense variants and CNVs represented 57.5%, 21.1% and 8.44% of association evidence, while CNVs conferred greatest relative risk. Meta-analysis with cohorts ascertained for developmental delay (DD) (n = 91,605) yielded 373 genes associated with ASD/DD at FDR ≤ 0.001 (664 at FDR ≤ 0.05), some of which differed in relative frequency of mutation between ASD and DD cohorts. The DD-associated genes were enriched in transcriptomes of progenitor and immature neuronal cells, whereas genes showing stronger evidence in ASD were more enriched in maturing neurons and overlapped with schizophrenia-associated genes, emphasizing that these neuropsychiatric disorders may share common pathways to risk

Neonatal outcomes for women at risk of preterm delivery given half dose versus full dose of antenatal betamethasone: a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial

International audienceBackgroundAntenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, reports of growth and neurodevelopmental dose-related side-effects suggest that the current dose (12 mg plus 12 mg, 24 h apart) might be too high. We therefore investigated whether a half dose would be non-inferior to the current full dose for preventing respiratory distress syndrome.MethodsWe designed a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial in 37 level 3 referral perinatal centres in France. Eligible participants were pregnant women aged 18 years or older with a singleton fetus at risk of preterm delivery and already treated with the first injection of antenatal betamethasone (11·4 mg) before 32 weeks’ gestation. We used a computer-generated code producing permuted blocks of varying sizes to randomly assign (1:1) women to receive either a placebo (half-dose group) or a second 11·4 mg betamethasone injection (full-dose group) 24 h later. Randomisation was stratified by gestational age (before or after 28 weeks). Participants, clinicians, and study staff were masked to the treatment allocation. The primary outcome was the need for exogenous intratracheal surfactant within 48 h after birth. Non-inferiority would be shown if the higher limit of the 95% CI for the between-group difference between the half-dose and full-dose groups in the primary endpoint was less than 4 percentage points (corresponding to a maximum relative risk of 1·20). Four interim analyses monitoring the primary and the secondary safety outcomes were done during the study period, using a sequential data analysis method that provided futility and non-inferiority stopping rules and checked for type I and II errors. Interim analyses were done in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT02897076.FindingsBetween Jan 2, 2017, and Oct 9, 2019, 3244 women were randomly assigned to the half-dose (n=1620 [49·9%]) or the full-dose group (n=1624 [50·1%]); 48 women withdrew consent, 30 fetuses were stillborn, 16 neonates were lost to follow-up, and 9 neonates died before evaluation, so that 3141 neonates remained for analysis. In the intention-to-treat analysis, the primary outcome occurred in 313 (20·0%) of 1567 neonates in the half-dose group and 276 (17·5%) of 1574 neonates in the full-dose group (risk difference 2·4%, 95% CI –0·3 to 5·2); thus non-inferiority was not shown. The per-protocol analysis also did not show non-inferiority (risk difference 2·2%, 95% CI –0·6 to 5·1). No between-group differences appeared in the rates of neonatal death, grade 3–4 intraventricular haemorrhage, stage ≥2 necrotising enterocolitis, severe retinopathy of prematurity, or bronchopulmonary dysplasia.InterpretationBecause non-inferiority of the half-dose compared with the full-dose regimen was not shown, our results do not support practice changes towards antenatal betamethasone dose reduction