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Light exposure affects the circadian system and consequently can affect sleep quality. Only few studies examined this relationship in children. We evaluated associations between light exposure patterns and sleep metrics in children. We measured the sleep parameters of 247 Dutch children, aged between 11 and 13 years and recruited from the ABCD cohort, using actigraphy and sleep records for 7 consecutive nights. Personal light exposures were measured with a light meter during the whole day and night. We applied generalized mixed-effects regression models, adjusted for possible confounders, to evaluate the associations of light exposure patterns on sleep duration, sleep efficiency and sleep-onset delay. In the models mutually adjusted for potential confounders, we found the amount of hours between the first time of bright light in the morning and going to sleep and the duration of bright light to be significantly associated with decreased sleep duration (in min; β: -2.02 [95% confidence interval: -3.84, -0.25], β: -8.39 [95% confidence interval: -16.70, -0.07], respectively) and with shorter sleep-onset delay (odds ratio: 0.88 [95% confidence interval: 0.80, 0.97], odds ratio: 0.40 [95% confidence interval: 0.19, 0.87], respectively). Increased light intensities at night were associated with decreased sleep duration (T2 β: -8.54 [95% confidence interval: -16.88, -0.20], T3 β: -14.83 [95% confidence interval: -28.04, -1.62]), while increased light intensities before going to bed were associated with prolonged sleep onset (odds ratio: 4.02 [95% confidence interval: 2.09, 7.73]). These findings further suggest that children may be able to influence their sleep quality by influencing the light exposure patterns during day and night., (© 2024 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Background: Environmental factors such as air pollution have been associated with Parkinson's disease (PD), but findings have been inconsistent. We investigated the association between exposure to several air pollutants, road traffic noise, and PD risk in two Dutch cohorts., Methods: Data from 50,087 participants from two Dutch population-based cohort studies, European Prospective Investigation into Cancer and Nutrition in the Netherlands and Arbeid, Milieu en Gezondheid Onderzoek were analyzed. In these cohorts, 235 PD cases were ascertained based on a previously validated algorithm combining self-reported information (diagnosis, medication, and symptoms) and registry data. We assigned the following traffic-related exposures to residential addresses at baseline: NO 2, NO x , particulate matter (PM) 2.5absorbance (as a marker for black carbon exposure), PM with aerodynamic diameter ≤2.5 µm (PM 2.5 ), ≤10 µm (PM 10 ), PM coarse (size fraction 2.5-10 µm), ultrafine particles <0.1 µm (UFP), and road traffic noise (L den ). Logistic regression models were applied to investigate the associations with PD, adjusted for possible confounders., Results: Both single- and two-pollutant models indicated associations between exposure to NO x , road traffic noise, and increasing odds of developing PD. Odds ratios of fully adjusted two-pollutant models in the highest compared with the lowest exposure quartile were 1.62 (95% CI = 1.02, 2.62) for NO x and 1.47 (95% CI = 0.97, 2.25) for road traffic noise, with clear trends across exposure categories., Conclusions: Our findings suggest that NO x and road traffic noise are associated with an increased risk of PD. While the association with NO x has been shown before, further investigation into the possible role of environmental noise on PD is warranted., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

With the aim to design new biologically active bioinorganic drugs of aspirin, whose mode of action is based on the inhibition of the cyclooxygenase(COX) enzymes, derivatives of Zeise's salt were synthesized in this structure-activity relationship study. Surprisingly, not only these Zeise-aspirin compounds but also Zeise's salt itself showed high inhibitory potency against COX enzymes in in vitro assays. In contrast, potassium tetrachloroplatinate and cisplatin did not influence the enzyme activity at equimolar concentrations. It was demonstrated by LC-ESI tandem-mass spectrometry that Zeise's salt platinates the essential amino acids Tyr385 (active site of the enzyme) and Ser516 (will be acetylated by aspirin) of COX-1, thereby strongly impairing the function of the enzyme. This finding demonstrates for the first time that Zeise's salt is pharmacologically active and is a potent enzyme inhibitor., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Metal complexes with N-heterocyclic carbene (NHC) ligands have been widely used in catalytic chemistry and are now increasingly considered for the development of new chemical tools and metal based drugs. Ruthenium complexes of the type (p-cymene)(NHC)RuCl(2) interacted with biologically relevant thiols and selenols, which resulted in the inhibition of enzymes such as thioredoxin reductase or cathepsin B. Pronounced antiproliferative effects could be obtained provided that an appropriate cellular uptake was achieved. Inhibition of tumor cell growth was accompanied by a perturbation of metabolic parameters such as cellular respiration.

An approach to characterize the interactions of RAPTA-T, a novel ruthenium-based anticancer drug candidate with intriguing antimetastatic properties, with human ovarian cancer cells in vitro is described. The distribution profile of the metallodrug within the cancer cells was determined by (size exclusion chromatography)-inductively coupled mass spectrometry combined with subcellular fractionation procedures (metallomics). Multidimensional protein identification technology (MudPIT) was then used to obtain insight into the alteration of the cellular proteome upon RAPTA-T treatment. The metallomics approach reveals striking differences in the intracellular behavior of the drug between cisplatin-sensitive and resistant cell lines and provides clues on possible mechanisms of action as well as detoxification, quantitative proteomics based on spectral counting sheds light on cellular response mechanisms to metallodrug treatment.

Gold(I) complexes with a 1,3-diethylbenzimidazol-2-ylidene N-heterocyclic carbene (NHC) ligand of the type NHC-Au-L (L=-Cl, -NHC, or -PPh3) were comparatively evaluated as thioredoxin reductase (TrxR) inhibitors and antimitochondrial anticancer agents. Different effects were noted in various biochemical assays (e.g., inhibition of TrxR, cellular and mitochondrial uptake, or effects on mitochondrial membrane potential), and this was related to properties of the complexes such as bond dissociation energies and overall charge. Remarkable antiproliferative effects, a strong induction of apoptosis, and enhancement of reactive oxygen species (ROS) formation as well as other effects on tumor cell metabolism confirmed the promising potential of the complexes as novel anticancer chemotherapeutics.

Cisplatin is undoubtedly one of the most common and successful anticancer drugs worldwide. Though its DNA-based mechanism of action is well established, the contribution of the proteome to this process remains unclear. The possible impact of particular Escherichia coli proteins on the cytostatic activity of cisplatin was the subject of this study. Our main focus was not only the "bottom-up" identification of novel cisplatin protein targets through LC/LC-MS/MS analysis, but also a label-free quantification of their regulation profile by spectral-counting. The regulation of two proteins, aconitate hydratase 2 and 60 kDa chaperonin 1, could be linked to a platinated amino acid in the protein sequence, whereas in the cases of 30S ribosomal protein S1 and enolase, it could be shown that cisplatin fragments are coordinated to an essential site for the functionality of the protein. Nucleoside triphosphate pyrophosphohydrolase (MazG) regulates the programmed cell death and was found to be platinated on the protein surface, which probably correlates with the established mode of action. A possible new chapter in the understanding of cisplatin's mechanism of action and its severe side effects is opened, since evidence is provided that platinated proteins are not only involved in cellular stress response but also in energy metabolism through glycolysis and catabolic processes, in gene regulatory mechanisms and protein synthesis., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Gold(I) complexes such as auranofin have been used for decades to treat symptoms of rheumatoid arthritis and have also demonstrated a considerable potential as new anticancer drugs. The enzyme thioredoxin reductase (TrxR) is considered as the most relevant molecular target for these species. The here investigated gold(I) complexes with benzimidazole derived N-heterocyclic carbene (NHC) ligands represent a promising class of gold coordination compounds with a good stability against the thiol glutathione. TrxR was selectively inhibited by in comparison to the closely related enzyme glutathione reductase, and all complexes triggered significant antiproliferative effects in cultured tumor cells. More detailed studies on a selected complex revealed a distinct pharmacodynamic profile including the high increase of reactive oxygen species formation, apoptosis induction, strong effects on cellular metabolism (related to cell surface properties, respiration, and glycolysis), inhibition of mitochondrial respiration and activity against resistant cell lines.