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In our previous studies, Prunus spinosa fruit (PSF) ethanol extract was showed to exert antioxidant, antimicrobial, anti-inflammatory and wound healing activities. In the present study, an integrated bioinformatics analysis combined with experimental validation was carried out to investigate the biological mechanism(s) that are responsible for the reported PSF beneficial effects as an antioxidant during a pro-inflammatory TLR4 insult. Bioinformatics analysis using miRNet 2.0 was carried out to address which biological process(es) the extract could be involved in. In addition, Chemprop was employed to identify the key targets of nuclear receptor (NR) signaling and stress response (SR) pathways potentially modulated. The miRNet analysis suggested that the PSF extract mostly activates the biological process of cellular senescence. The Chemprop analysis predicted three possible targets for nine phytochemicals found in the extract: (i) ARE signaling, (ii) mitochondrial membrane potential (MMP) and (iii) p53 SR pathways. The PSF extract antioxidant effect was also experimentally validated in vitro using the human monocyte U937 cell line. Our findings showed that Nrf2 is modulated by the extract with a consequent reduction of the oxidative stress level. This was confirmed by a strong decrease in the amount of reactive oxygen species (ROS) observed in the PSF-treated cells subjected to lipopolysaccharide (LPS) (6 h treatment, 1 µg/mL). No visible effects were observed on p53 and MMP modulation. [ABSTRACT FROM AUTHOR]

The nuclear RNA surveillance mechanism is essential for cancer cell survival and is ensured by the RNA nuclear exosome including some co‐factors, such as the RNA helicase MTR4. Recent studies suggest an involvement of DNA repair proteins such as apurinic/apyrimidinic (AP) endodeoxyribonuclease 1 (APE1), a major endodeoxyribonuclease of Base Excision Repair (BER), in RNA metabolism and RNA decay of oxidized and abasic RNA. Cisplatin (CDDP) and 5‐fluorouracil (5‐FU) are commonly used for the treatment of solid tumours. Whether APE1 is involved in the elimination of CDDP‐ or 5‐FU‐damaged RNA is unknown, as is its possible interaction with the nuclear exosome complex. Here, by using different human cancer cell models, we demonstrated that: (a) APE1 is involved in the elimination of damaged‐RNA, upon CDDP‐ and 5‐FU‐treatments, in a MTR4‐independent manner; (b) the interaction between APE1 and MTR4 is stimulated by CDDP‐ and 5‐FU‐treatments through lysine residues in the APE1 N‐terminal region and is, in part, mediated by nucleic acids and (c) APE1‐ and MTR4‐depletion lead to the generation of R‐loop formation causing the activation of the DNA damage response (DDR) pathway through the ATM‐p53‐p21 axis. Our data demonstrate a role of MTR4 in DDR underpinning the function of APE1 in controlling the RNA quality upon genotoxic treatments with possible implications in chemoresistance. [ABSTRACT FROM AUTHOR]

Fruit derivatives are commonly obtained by applying processing operations deemed responsible for the loss of phenol compounds, but very little information is available on the fate of phenols upon digestion of these products. The present study evaluated the effect of thermal and mechanical treatments, commonly applied to turn apple pulp into puree and homogenate, on phenolic bioaccessibility and antioxidant activity. Despite a 20 % decrease in polyphenols due to processing, their bioaccessibility was higher in apple derivatives (>20 %) compared to pulp (∼2 %). Polyphenol oxidase (PPO), inactivated by thermal treatments in apple derivatives but not in the pulp, was hypothesized to be responsible for this difference. Results acquired on an unprocessed PPO-free apple model, only featuring quercetin-3-glucoside and pectin, actually exhibited similar bioaccessibility as processed derivatives. The radical scavenging capacity was unaffected by the structural integrity of apples, indicating independence from the plant tissue's hierarchical arrangement. After digestion, radical scavenging capacity decreased in the real apple matrices, correlating with phenolic content, while it was retained in the apple model, further suggesting the pivotal food matrix role in modulating polyphenols bioaccessibility and subsequent biological activity. Translating these results to an industrial scale, processing conditions can be optimized not only to guarantee that the quality requirements are met, but also to achieve desired nutritional benefits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)