90 research outputs found
Polyphenols from Cocoa and Vascular Health—A Critical Review
Cocoa is a rich source of dietary polyphenols. In vitro as well as cell culture data indicate that cocoa polyphenols may exhibit antioxidant and anti-inflammatory, as well as anti-atherogenic activity. Several molecular targets (e.g., nuclear factor kappa B, endothelial nitric oxide synthase, angiotensin converting enzyme) have been recently identified which may partly explain potential beneficial cardiovascular effects of cocoa polyphenols. However cocoa polyphenol concentrations, as used in many cell culture studies, are not physiologically achievable. Bioavailability studies indicate that plasma concentrations of cocoa polyphenols following dietary intake are low and in the nanomolar range. Human studies regarding the effect of cocoa polyphenols on vascular health are often underpowered and lack a rigorous study design. If dietary cocoa polyphenol intake is due to chocolate its high energy content needs to be taken into account. In order to determine potential health benefits of cocoa polyphenols large scale, long term, randomized, placebo controlled studies, (ideally with a cross-over design) as well as prospective studies are warranted
Morphological characteristics, bioactive compounds content, and antioxidant activity of different accessions of African eggplant (Solanum anguivi Lam.)
African eggplant (Solanum anguivi Lam.) fruits reportedly exhibit antidiabetic properties, possibly due to the presence of bioactive compounds. This study aimed to assess the bioactive compounds content (BCC) and antioxidant activity (AA) in the fruits of fourteen African eggplant accessions. The relationship between the fruit BCC and AA, and the plant (leaf, stem and fruit) morphological characteristics was determined. Morphological traits for the plant accessions were characterized based on existing Solanum species descriptors. Total phenolics, flavonoids, saponins, vitamin C and AA were determined by spectrophotometry, while total alkaloids were detected by gravimetry. HPLC was used for the quantification of phenolic compounds. Morphological characteristics, BCC and AA differed among the accessions. The fruit’s accessions contained total phenolics (8.0-12.4 mg gallic acid equivalent/g dry weight (DW)), saponins (51.1-124.8 mg diosgenin equivalent/g DW), alkaloids (81.4-127.7 mg/g DW), vitamin C (3.6-6.4 mg ascorbic acid equivalent/g DW), and flavonoids (0.9-2.1 mg quercetin equivalent (QE)/ g DW) and exhibited a high AA (1.2-4.6 mg QE/g DW). Amongst the quantified phenolic compounds, chlorogenic acid (21.4-301.3 μg/ g DW) had the highest content. Cluster analyses showed that morphological characteristics might be useful to predict accessions with similar BCC and AA. Accessions with high total phenolics provided the highest AA, and, therefore, may mediate health benefits
Chemical Characterization, Free Radical Scavenging, and Cellular Antioxidant and Anti-Inflammatory Properties of a Stilbenoid-Rich Root Extract of Vitis vinifera
Dietary stilbenoids are receiving increasing attention due to their potential health benefits. However, most studies concerning the bioactivity of stilbenoids were conducted with pure compounds, for example, resveratrol. The aim of this study was to characterize a complex root extract of Vitis vinifera in terms of its free radical scavenging and cellular antioxidant and anti-inflammatory properties. HPLC-ESI-MS/MS analyses of the root extract of Vitis vinifera identified seven stilbenoids including two monomeric (resveratrol and piceatannol), two dimeric (trans-ɛ-viniferin and ampelopsin A), one trimeric (miyabenol C), and two tetrameric (r-2-viniferin = vitisin A and r-viniferin = vitisin B) compounds which may mediate its biological activity. Electron spin resonance and spin trapping experiments indicate that the root extract scavenged 2,2-diphenyl-1-picrylhydrazyl, hydroxyl, galvinoxyl, and superoxide free radicals. On a cellular level it was observed that the root extract of Vitis vinifera protects against hydrogen peroxide-induced DNA damage and induces Nrf2 and its target genes heme oxygenase-1 and γ-glutamylcysteine synthetase. Furthermore, the root extract could induce the antiatherogenic hepatic enzyme paraoxonase 1 and downregulate proinflammatory gene expression (interleukin 1β, inducible nitric oxide synthase) in macrophages. Collectively our data suggest that the root extract of Vitis vinifera exhibits free radical scavenging as well as cellular antioxidant and anti-inflammatory properties
Stress Resistance and Longevity Are Not Directly Linked to Levels of Enzymatic Antioxidants in the Ponerine Ant Harpegnathos saltator
BACKGROUND: The molecular mechanisms of variations in individual longevity are not well understood, even though longevity can be increased substantially by means of diverse experimental manipulations. One of the factors supposed to be involved in the increase of longevity is a higher stress resistance. To test this hypothesis in a natural system, eusocial insects such as bees or ants are ideally suited. In contrast to most other eusocial insects, ponerine ants show a peculiar life history that comprises the possibility to switch during adult life from a normal worker to a reproductive gamergate, therewith increasing their life expectancy significantly. RESULTS: We show that increased resistance against major stressors, such as reactive oxygen species and infection accompanies the switch from a life-history trait with normal lifespan to one with a longer life expectancy. A short period of social isolation was sufficient to enhance stress resistance of workers from the ponerine ant species Harpegnathos saltator significantly. All ant groups with increased stress resistances (reproducing gamergates and socially isolated workers) have lower catalase activities and glutathione levels than normal workers. Therewith, these ants resemble the characteristics of the youngest ants in the colony. CONCLUSIONS: Social insects with their specific life history including a switch from normal workers to reproducing gamergates during adult life are well suited for ageing research. The regulation of stress resistance in gamergates seemed to be modified compared to foraging workers in an economic way. Interestingly, a switch towards more stress resistant animals can also be induced by a brief period of social isolation, which may already be associated with a shift to a reproductive trajectory. In Harpegnathos saltator, stress resistances are differently and potentially more economically regulated in reproductive individuals, highlighting the significance of reproduction for an increase in longevity in social insects. As already shown for other organisms with a long lifespan, this trait is not directly coupled to higher levels of enzymatic and non-enzymatic antioxidants
Calibration by differentiation – Self‐supervised calibration for X‐ray microscopy using a differentiable cone‐beam reconstruction operator
High‐resolution X‐ray microscopy (XRM) is gaining interest for biological investigations of extremely small‐scale structures. XRM imaging of bones in living mice could provide new insights into the emergence and treatment of osteoporosis by observing osteocyte lacunae, which are holes in the bone of few micrometres in size. Imaging living animals at that resolution, however, is extremely challenging and requires very sophisticated data processing converting the raw XRM detector output into reconstructed images. This paper presents an open‐source, differentiable reconstruction pipeline for XRM data which analytically computes the final image from the raw measurements. In contrast to most proprietary reconstruction software, it offers the user full control over each processing step and, additionally, makes the entire pipeline deep learning compatible by ensuring differentiability. This allows fitting trainable modules both before and after the actual reconstruction step in a purely data‐driven way using the gradient‐based optimizers of common deep learning frameworks. The value of such differentiability is demonstrated by calibrating the parameters of a simple cupping correction module operating on the raw projection images using only a self‐supervisory quality metric based on the reconstructed volume and no further calibration measurements. The retrospective calibration directly improves image quality as it avoids cupping artefacts and decreases the difference in grey values between outer and inner bone by 68–94%. Furthermore, it makes the reconstruction process entirely independent of the XRM manufacturer and paves the way to explore modern deep learning reconstruction methods for arbitrary XRM and, potentially, other flat‐panel computed tomography systems. This exemplifies how differentiable reconstruction can be leveraged in the context of XRM and, hence, is an important step towards the goal of reducing the resolution limit of in vivo bone imaging to the single micrometre domain
Aerosol-cloud-radiation interaction during Saharan dust episodes: The dusty cirrus puzzle
Dusty cirrus clouds are extended optically thick cirrocumulus decks that occur during strong mineral dust events. So far they have been mostly documented over Europe associated with dust-infused baroclinic storms. Since today's numerical weather prediction models neither predict mineral dust distributions nor consider the interaction of dust with cloud microphysics, they cannot simulate this phenomenon. We postulate that the dusty cirrus forms through a mixing instability of moist clean air with drier dusty air. A corresponding sub-grid parameterization is suggested and tested in the ICON-ART model. Only with help of this parameterization ICON-ART is able to simulate the formation of the dusty cirrus, which leads to substantial improvements in cloud cover and radiative fluxes compared to simulations without this parameterization. A statistical evaluation over six Saharan dust events with and without observed dusty cirrus shows robust improvements in cloud and radiation scores. The ability to simulate dusty cirrus formation removes the linear dependency on mineral dust aerosol optical depth from the bias of the radiative fluxes. This suggests that the formation of dusty cirrus clouds is the dominant aerosol-cloud-radiation effect of mineral dust over Europe.</p
Atlantic Salmon (Salmo salar L.) as a Marine Functional Source of Gamma-Tocopherol
Gamma tocopherol (gT) exhibits beneficial cardiovascular effects partly due to its anti-inflammatory activity. Important sources of gT are vegetable oils. However, little is known to what extent gT can be transferred into marine animal species such as Atlantic salmon by feeding. Therefore, in this study we have investigated the transfer of dietary gT into salmon. To this end, fish were fed a diet supplemented with 170 ppm gT for 16 weeks whereby alpha tocopherol levels were adjusted to 190 ppm in this and the control diet. Feeding gT-rich diets resulted in a three-fold increase in gT concentrations in the liver and fillet compared to non-gT-supplemented controls. Tissue alpha tocopherol levels were not decreased indicating no antagonistic interaction between gamma- and alpha tocopherol in salmon. The concentration of total omega 3 fatty acids slightly increased in response to dietary gT. Furthermore, dietary gT significantly decreased malondialdehyde in the fillet, determined as a biomarker of lipid peroxidation. In the liver of gT fed salmon we observed an overall down-regulation of genes involved in lipid homeostasis. Additionally, gT improved the antioxidant capacity by up-regulating Gpx4a gene expression in the pyloric caeca. We suggest that Atlantic salmon may provide a marine functional source capable of enriching gT for human consumption
Epigallocatechin gallate (EGCG) affects glucose metabolism and enhances fitness and life span in Drosophila melanogaster
In this study, we tested whether a standardized epigallocatechin-3-gallate (EGCG) rich green tea extract (comprising > 90% EGCG) affects fitness and lifespan as well as parameters of glucose metabolism and energy homeostasis in the fruit fly, Drosophila melanogaster. Following the application of the green tea extract a significant increase in the mean lifespan (+ 3.3 days) and the 50% survival (+ 4.3 days) as well as improved fitness was detected. These effects went along an increased expression of Spargel, the homolog of mammalian PGC1α, which has been reported to affect lifespan in flies. Intriguingly, in flies, treatment with the green tea extract decreased glucose concentrations, which were accompanied by an inhibition of α-amylase and α-glucosidase activity. Computational docking analysis proved the potential of EGCG to dock into the substrate binding pocket of α-amylase and to a greater extent into α-glucosidase. Furthermore, we demonstrate that EGCG downregulates insulin-like peptide 5 and phosphoenolpyruvate carboxykinase, major regulators of glucose metabolism, as well as the Drosophila homolog of leptin, unpaired 2. We propose that a decrease in glucose metabolism in connection with an upregulated expression of Spargel contribute to the better fitness and the extended lifespan in EGCG-treated flies
Central memory phenotype drives success of checkpoint inhibition in combination with CAR T cells
The immunosuppressive microenvironment in solid tumors is thought to form a barrier to the entry and efficacy of cell-based therapies such as chimeric antigen receptor (CAR) T cells. Combining CAR T cell therapy with checkpoint inhibitors has been demonstrated to oppose immune escape mechanisms in solid tumors and augment antitumor efficacy. We evaluated PD-1/PD-L1 signaling capacity and the impact of an inhibitor of this checkpoint axis in an in vitro system for cancer cell challenge, the coculture of L1CAM-specific CAR T cells with neuroblastoma cell lines. Fluorescence-activated cell sorting-based analyses and luciferase reporter assays were used to assess PD-1/PD-L1 expression on CAR T and tumor cells as well as CAR T cell ability to kill neuroblastoma cells. Coculturing neuroblastoma cell lines with L1CAM-CAR T cells upregulated PD-L1 expression on neuroblastoma cells, confirming adaptive immune resistance. Exposure to neuroblastoma cells also upregulated the expression of the PD-1/PD-L1 axis in CAR T cells. The checkpoint inhibitor, nivolumab, enhanced L1CAM-CAR T cell-directed killing. However, nivolumab-enhanced L1CAM-CAR T cell killing did not strictly correlate with PD-L1 expression on neuroblastoma cells. In fact, checkpoint inhibitor success relied on strong PD-1/PD-L1 axis expression in the CAR T cells, which in turn depended on costimulatory domains within the CAR construct, and more importantly, on the subset of T cells selected for CAR T cell generation. Thus, T cell subset selection for CAR T cell generation and CAR T cell prescreening for PD-1/PD-L1 expression could help determine when combination therapy with checkpoint inhibitors could improve treatment efficacy
A Novel Labeling Approach Identifies Three Stability Levels of Acetylcholine Receptors in the Mouse Neuromuscular Junction In Vivo
The turnover of acetylcholine receptors at the neuromuscular junction is regulated in an activity-dependent manner. Upon denervation and under various other pathological conditions, receptor half-life is decreased., in our setup the same animals are used throughout the whole measurement period, thereby permitting a dramatic reduction of animal numbers at increased data quality. We identified three stability levels of acetylcholine receptors depending on the presence or absence of innervation: one pool of receptors with a long half-life of ∼13 days, a second with an intermediate half-life of ∼8 days, and a third with a short half-life of ∼1 day. Data were highly reproducible from animal to animal and followed simple exponential terms. The principal outcomes of these measurements were reproduced by an optical pulse-labeling assay introduced recently.A novel assay to determine kinetics of acetylcholine receptor turnover with small animal numbers is presented. Our data show that nerve activity acts on muscle acetylcholine receptor stability by at least two different means, one shifting receptor lifetime from short to intermediate and another, which further increases receptor stability to a long lifetime. We hypothesize on possible molecular mechanisms
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