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The adaptation to hypoxia is mainly controlled by the HIF transcription factors. Increased expression/activity of HIF-1α correlates with poor prognosis in cancer patients. PARP-1 inhibitors are used in the clinic to treat BRCAness breast/ovarian cancer and have been shown to regulate the hypoxic response; therefore, their use could be expanded.
In this work by integrating molecular/cell biology approaches, genome-wide ChIP-seq, and patient samples, we elucidate the extent to which PARP-1 exerts control over HIF-1-regulated genes.
In human melanoma, PARP-1 and HIF-1α expression are strongly associated. In response to a hypoxic challenge poly(ADP-ribose) (PAR) is synthesized, HIF-1α is post-transcriptionally modified (PTM) and stabilized by PARylation at specific K/R residues located at its C-terminus. Using an unbiased ChIP-seq approach we demonstrate that PARP-1 dictates hypoxia-dependent HIF-recruitment to chromatin in a range of HIF-regulated genes while analysis of HIF-binding motifs (RCGTG) reveals a restriction on the recognition of hypoxia responsive elements in the absence of PARP-1. Consequently, the cells are poorly adapted to hypoxia, showing a reduced fitness during hypoxic induction.
These data characterize the fine-tuning regulation by PARP-1/PARylation of HIF activation and suggest that PARP inhibitors might have therapeutic potential against cancer types displaying HIF-1α over-activation.
These data characterize the fine-tuning regulation by PARP-1/PARylation of HIF activation and suggest that PARP inhibitors might have therapeutic potential against cancer types displaying HIF-1α over-activation.Several changes can take place in wine after blotting. Some of them lead to the desired evolution of wine being more complex, round and pleasant. However, unexpected changes can also occur ascribable to the premature wine oxidation (PremOx) arising when a wine, presumably with aging potential, results oxidized and often undrinkable. The complexity of PremOx, where aromas are also involved, makes difficult to identify all the oxidation products, and to predict its occurrence in wines. Despite most studies have been focused on the effect of time after wine bottling on PremOx as well as pinking phenomena, identification of pinking markers, reliable methods for their detection in wine, and correlations between markers and the wine-bottle-closure system are still unknown. This review aimed to highlight aspects PremOx-related, including wine-bottle-closure system, color change, with particular emphasis on pinking, and aroma decay based on the current knowledge becoming the bases for future perspectives.Graphene oxide (GO) and GO-based materials have shown excellent adsorption properties because of bounteous structure and rich oxygen functional groups. Many studies have shown that GO are utilized as adsorbents to remove organic dyes from wastewater. GO was prepared by modified Hummers method using graphite powder as raw material. On this basis, β-cyclodextrin/graphene oxide composite (β-CD/GO) was prepared by modifying graphene oxide via β-cyclodextrin(β-CD) crosslinking method. GO and β-CD were characterized by Fourier transform infrared spectroscopy (FT-IR), energy-dispersive X-ray (XRD), scanning electron (SEM) and thermogravimetric analysis (TGA). Their adsorbents properties have been studied with methylene blue (MB) as adsorbate. The factors affecting the study include the temperature, adsorption time, amount of adsorbent and system pH value. Adsorption isotherm and kinetics of the adsorption process are systematically analyzed. The results show that β-CD/GO has a different adsorption capacity from GO under the same adsorption factors. Under the optimized conditions (the reaction temperature is 70 °C, the reaction time is 60 min and the concentration of adsorbent is 0.04 g/L), the removal efficiency of β-CD/GO is 20% higher than that of GO from 70% to 90%. The maximum adsorption capacity of β-CD/GO is 76.4 mg/g. β-CD/GO can be effectively regenerated by elution with absolute alcohol. In these tests, β-CD/GO was suggested to be more efficient than GO in the removal of organic dyes.Photochemoprotection of the skin can be achieved by inhibiting inflammation and oxidative stress, which we tested using Cordia verbenacea extract, a medicinal plant known for its rich content of antioxidant molecules and anti-inflammatory activity. find more In vitro antioxidant evaluation of Cordia verbenacea leaves ethanolic extract (CVE) presented the following results ferric reducing antioxidant power (886.32 μM equivalent of Trolox/g extract); IC50 of 19.128 μg/ml for scavenging 2,2-diphenyl-1-picrylhydrazyl; IC50 of 12.48 μg/mL for scavenging 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid); decrease of hydroperoxides from linoleic acid (IC50 of 10.20 μg/mL); inhibition of thiobarbituric acid reactive substances (IC50 8.90 μg/mL); iron-chelating ability in bathophenanthroline iron assay (IC50 47.35 μg/mL); chemiluminescence triggered by free radicals in the H2O2/horseradish peroxidase/luminol (IC50 0.286 μg/mL) and xanthine/xanthine oxidase/luminol (IC50 0.42 μg/mL) methods. CVE (10-100 mg per kg, 30 min before and immediately after UVB exposure) treatment was performed by gavage in hairless mice. CVE inhibited skin edema, neutrophil infiltration, and overproduction of MMP-9; reduced levels of TNF-α, IL-1β, and IL- 6; numbers of skin mast cells, epidermal thickening, number of epidermal apoptotic keratinocytes, and collagen degradation. CVE increased the skin's natural antioxidant defenses as observed by Nrf-2, NAD(P)H quinone oxidoreductase 1, and heme oxygenase 1 mRNA expression enhancement. Furthermore, CVE inhibited lipid peroxidation and superoxide anion production and recovered antioxidant reduced glutathione, catalase activity, and ROS scavenging capacity of the skin. Concluding, CVE downregulates the skin inflammatory and oxidative damages triggered by UVB, demonstrating its potentialities as a therapeutic approach.
The Protective Behavioral Strategies for Marijuana Scale (PBSM), a 17-item scale targeting strategies for mitigating the negative consequences of cannabis use, highlights a range of behaviors that can reduce harm beyond straightforward decreases in quantity or frequency. The 17-item scale's factor structure remains under-examined but could reveal meaningful distinctions among strategies. This study aimed to confirm the factor structure of the short form of the PBSM.
This study recruited cannabis-using undergraduates (N=454,M
=19.6, 68.8% female, 39% White), who reported using cannabis approximately 2.3days per week with mild cannabis-related consequences (CAPQ; M=9.74).
A confirmatory factor analysis demonstrated poor fit for the one-factor model of the PBSM, prompting an exploratory factor analysis. Analyses revealed two internally reliable factors a "Quantity" factor, strategies specific to mitigating overuse and limiting amounts consumed and an "Context" factor loosely related to troubles with others.
Read More: https://www.selleckchem.com/products/sbp-7455.html
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