216 research outputs found

    Carbon nanotubes quench singlet oxygen generated by photosynthetic reaction centers

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    Photosensitizers may convert molecular oxygen into reactive oxygen species (ROS) including, e.g., singlet oxygen (1O2), superoxide anion (O2-•), and hydroxyl radicals (•OH), chemicals with extremely high cyto- and potential genotoxicity. Photodynamic ROS reactions are determinative in medical photodynamic therapy (cancer treatment with externally added photosensitizers) and in reactions damaging the photosynthetic apparatus of plants (via internal pigments). The primary events of photosynthesis take place in the chlorophyll containing reaction center protein complex (RC), where the energy of light is converted into chemical potential. 1O2 is formed by both bacterial bacteriochlorophylls and plant RC triplet chlorophylls in high light and if the quenching of 1O2 is impaired. In plant physiology, reducing the formation of the ROS and thus lessening photooxidative membrane damage (including the RC protein) and increasing the efficiency of the photochemical energy conversion is of special interest. Carbon nanotubes, in artificial systems, are also known to react with singlet oxygen. To investigate the possibility of 1O2 quenching by carbon nanotubes in a biological system, we studied the effect of carbon nanotubes on 1O2 photogenerated by photosynthetic RCs purified from purple bacteria. 1,3-Diphenylisobenzofuran (DPBF), a dye responding to oxidation by 1O2 with absorption decrease at 420nm was used to measure 1O2 concentrations. 1O2 was produced either from a photosensitizer (methylene blue) or from triplet photosynthetic RCs and the antioxidant capacity of carbon nanotubes was assessed. Less 1O2 was detected by DPBF in the presence of carbon nanotubes, suggesting that these are potential quenchers of this ROS. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

    Ecto-nucleoside triphosphate diphosphohydrolase 3 in the ventral and lateral hypothalamic area of female rats: morphological characterization and functional implications

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    <p>Abstract</p> <p>Background</p> <p>Based on its distribution in the brain, ecto-nucleoside triphosphate diphosphohydrolase 3 (NTPDase3) may play a role in the hypothalamic regulation of homeostatic systems, including feeding, sleep-wake behavior and reproduction. To further characterize the morphological attributes of NTPDase3-immunoreactive (IR) hypothalamic structures in the rat brain, here we investigated: 1.) The cellular and subcellular localization of NTPDase3; 2.) The effects of 17β-estradiol on the expression level of hypothalamic NTPDase3; and 3.) The effects of NTPDase inhibition in hypothalamic synaptosomal preparations.</p> <p>Methods</p> <p>Combined light- and electron microscopic analyses were carried out to characterize the cellular and subcellular localization of NTPDase3-immunoreactivity. The effects of estrogen on hypothalamic NTPDase3 expression was studied by western blot technique. Finally, the effects of NTPDase inhibition on mitochondrial respiration were investigated using a Clark-type oxygen electrode.</p> <p>Results</p> <p>Combined light- and electron microscopic analysis of immunostained hypothalamic slices revealed that NTPDase3-IR is linked to ribosomes and mitochondria, is predominantly present in excitatory axon terminals and in distinct segments of the perikaryal plasma membrane. Immunohistochemical labeling of NTPDase3 and glutamic acid decarboxylase (GAD) indicated that γ-amino-butyric-acid- (GABA) ergic hypothalamic neurons do not express NTPDase3, further suggesting that in the hypothalamus, NTPDase3 is predominantly present in excitatory neurons. We also investigated whether estrogen influences the expression level of NTPDase3 in the ventrobasal and lateral hypothalamus. A single subcutaneous injection of estrogen differentially increased NTPDase3 expression in the medial and lateral parts of the hypothalamus, indicating that this enzyme likely plays region-specific roles in estrogen-dependent hypothalamic regulatory mechanisms. Determination of mitochondrial respiration rates with and without the inhibition of NTPDases confirmed the presence of NTPDases, including NTPDase3 in neuronal mitochondria and showed that blockade of mitochondrial NTPDase functions decreases state 3 mitochondrial respiration rate and total mitochondrial respiratory capacity.</p> <p>Conclusion</p> <p>Altogether, these results suggest the possibility that NTPDases, among them NTPDase3, may play an estrogen-dependent modulatory role in the regulation of intracellular availability of ATP needed for excitatory neuronal functions including neurotransmission.</p

    Association of Maternal Autoimmune Diseases With Risk of Mental Disorders in Offspring in Denmark

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    IMPORTANCE Maternal immune activation during pregnancy is associated with increased risks of several mental disorders in offspring during childhood, but little is known about how maternal autoimmune diseases during pregnancy are associated with mental health in offspring during and after childhood.OBJECTIVE To investigate the association between maternal autoimmune diseases before childbirth and risk of mental disorders among offspring up to early adulthood.DESIGN, SETTING, AND PARTICIPANTS This population-based nationwide cohort study used data from Danish national registers on singletons born in Denmark from 1978 to 2015 with up to 38 years of follow-up. Data analyses were conducted from March 1, 2020, through September 30, 2021.EXPOSURES Maternal autoimmune disease diagnosed before or during pregnancy according to the Danish National Patient Register.MAIN OUTCOMES AND MEASURES The main outcome was mental disorders, defined by hospital diagnoses, in offspring. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for mental disorders.RESULTS Of the 2 254 234 singleton infants included in the study (median age, 16.7 years [IQR, 10.5-21.7 years]; 51.28% male), 2.26% were born to mothers with autoimmune diseases before childbirth. Exposed participants had an increased risk of overall mental disorders compared with their unexposed counterparts (HR, 1.16; 95% CI, 1.13-1.19; incidence, 9.38 vs 7.91 per 1000 person-years). Increased risks of overall mental disorders in offspring were seen in different age groups for type 1 diabetes (1-5 years: HR, 1.35 [95% CI, 1.17-1.57]; 6-18 years: HR, 1.24 [95% CI, 1.15-1.33]; >18 years: HR, 1.19 [95% CI, 1.09-1.30]) and rheumatoid arthritis (1-5 years: HR, 1.42 [95% CI, 1.16-1.74]; 6-18 years: HR, 1.19 [95% CI, 1.05436]; >18 years: HR, 1.28 [95% CI, 1.02-1.60]). Regarding specific mental disorders, increased risk after exposure to any maternal autoimmune disorder was observed for organic disorders (HR, 1.54; 95% CI, 1.21-1.94), schizophrenia (HR, 1.35; 95% CI, 1.21-1.51), obsessive-compulsive disorder (HR, 1.42; 95% CI, 1.24-1.63), mood disorders (HR, 1.12; 95% CI, 1.04-121), and a series of neurodevelopmental disorders (eg, childhood autism [HR, 1.21; 95% CI, 1.08436] and attention-deficit/hyperactivity disorder [HR, 1.19; 95% CI, 1.12-1.26]).CONCLUSIONS AND RELEVANCE In this cohort study in Denmark, prenatal exposure to maternal autoimmune diseases was associated with increased risks of overall and type-specific mental disorders in offspring. Maternal type 1 diabetes and rheumatoid arthritis during pregnancy were associated with offspring's mental health up to early adulthood. Individuals prenatally exposed to autoimmune disease may benefit from long-term surveillance for mental disorders.</p

    Small extracellular vesicles convey the stress-induced adaptive responses of melanoma cells

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    Exosomes are small extracellular vesicles (sEVs), playing a crucial role in the intercellular communication in physiological as well as pathological processes. Here, we aimed to study whether the melanoma-derived sEV-mediated communication could adapt to microenvironmental stresses. We compared B16F1 cell-derived sEVs released under normal and stress conditions, including cytostatic, heat and oxidative stress. The miRNome and proteome showed substantial differences across the sEV groups and bioinformatics analysis of the obtained data by the Ingenuity Pathway Analysis also revealed significant functional differences. The in silico predicted functional alterations of sEVs were validated by in vitro assays. For instance, melanoma-derived sEVs elicited by oxidative stress increased Ki-67 expression of mesenchymal stem cells (MSCs); cytostatic stress-resulted sEVs facilitated melanoma cell migration; all sEV groups supported microtissue generation of MSC-B16F1 co-cultures in a 3D tumour matrix model. Based on this study, we concluded that (i) molecular patterns of tumour-derived sEVs, dictated by the microenvironmental conditions, resulted in specific response patterns in the recipient cells; (ii) in silico analyses could be useful tools to predict different stress responses; (iii) alteration of the sEV-mediated communication of tumour cells might be a therapy-induced host response, with a potential influence on treatment efficacy.Peer reviewe

    Tomato Landraces May Benefit from Protected Production—Evaluation on Phytochemicals

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    Plant genetic resources (PGRs) serving as a wide genetic pool of tomato germplasm can provide a solid base for recent breeding efforts to increase consumer acceptance towards the taste and the phytonutrient properties of novel tomato varieties. Old varieties and landraces were abandoned by producers due to unfavorable phenotypic characteristics; however, their high adaptability and nutritional properties are inevitably valuable. This study aims to investigate the impact of open-field vs. protected production on various bioactive compound parameters and on the antioxidant status of seven indeterminate-type tomato PGRs in an organic production system for two years (2015–2016). Genotype main effect plus genotype × environment interaction (GGE) biplots were created for visualizing the which-won-where concept of the PGRs investigated. The GGE analysis revealed that the phytonutrient content of certain PGRs is less dependent on location and more influenced by differences in microclimatic conditions. “Balatonboglár”, “Mátrafüred” and “Fadd” PGRs performed better in a polytunnel, while Tarnaméra provided better results in an open field. “Máriapócs” and “San Marzano” showed a relative independence from production location in terms of their measured phytonutrient values. These findings enrich the nutritional datasets of tomato landraces, which support the in situ conservation and utilization of PGRs in breeding programs

    Novel Neuroprotective Strategies in Ischemic Retinal Lesions

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    Retinal ischemia can be effectively modeled by permanent bilateral common carotid artery occlusion, which leads to chronic hypoperfusion-induced degeneration in the entire rat retina. The complex pathways leading to retinal cell death offer a complex approach of neuroprotective strategies. In the present review we summarize recent findings with different neuroprotective candidate molecules. We describe the protective effects of intravitreal treatment with: (i) urocortin 2; (ii) a mitochondrial ATP-sensitive K+ channel opener, diazoxide; (iii) a neurotrophic factor, pituitary adenylate cyclase activating polypeptide; and (iv) a novel poly(ADP-ribose) polymerase inhibitor (HO3089). The retinoprotective effects are demonstrated with morphological description and effects on apoptotic pathways using molecular biological techniques
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