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- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseasesPublication . Rojo, Ana I.; Buttari, Brigitta; Cadenas, Susana; Carlos, Ana Rita; Cuadrado, Antonio; Falcão, Ana Sofia; López, Manuela G.; Georgiev, Milen I.; Grochot-Przeczek, Anna; Gumeni, Sentiljana; Jimenez-Villegas, José; Horbanczuk, Jarosław Olav; Konu, Ozlen; Lastres-Becker, Isabel; Levonen, Anna-Liisa; Maksimova, Viktorija; Michaeloudes, Charalambos; Mihaylova, Liliya V.; Mickael, Michel Edwar; Milisav, Irina; Miova, Biljana; Rada, Patricia; Santos, Marlene; Seabra, Miguel C.; Strac, Dubravka Svob; Tenreiro, Sandra; Trougakos, Ioannis P.; Dinkova-Kostova, Albena T.Non-communicable chronic diseases (NCDs) are most commonly characterized by agerelated loss of homeostasis and/or by cumulative exposures to environmental factors, which lead to low-grade sustained generation of reactive oxygen species (ROS), chronic inflammation and metabolic imbalance. Nuclear factor erythroid 2-like 2 (NRF2) is a basic leucine-zipper transcription factor that regulates the cellular redox homeostasis. NRF2 controls the expression of more than 250 human genes that share in their regulatory regions a cis-acting enhancer termed the antioxidant response element (ARE). The products of these genes participate in numerous functions including biotransformation and redox homeostasis, lipid and iron metabolism, inflammation, proteostasis, as well as mitochondrial dynamics and energetics. Thus, it is possible that a single pharmacological NRF2 modulator might mitigate the effect of the main hallmarks of NCDs, including oxidative, proteostatic, inflammatory and/or metabolic stress. Research on model organisms has provided tremendous knowledge of the molecular mechanisms by which NRF2 affects NCDs pathogenesis. This review is a comprehensive summary of the most commonly used model organisms of NCDs in which NRF2 has been genetically or pharmacologically modulated, paving the way for drug development to combat NCDs. We discuss the validity and use of these models and identify future challenges.
- Warfarin–Supplement Interactions: A Systematic ReviewPublication . Alves, Pedro; Carreira, Bruno; Nogueira, Gonçalo; Sousa, Mariana; Cruz, Agotinho; Cruz, AgostinhoFood supplements, which are concentrated forms of nutrients, play a crucial role in maintaining a balanced diet by providing essential missing nutrients. However, their impact on drug interactions cannot be overlooked. One such drug is warfarin, which is an anticoagulant with a complex interplay involving various medications, foods, and supplements. Given the significant increase in the use of dietary supplements in reent years, there is a compelling rationale to investigate their interactions with warfarin. This systematic review aims to identify supplements that interact with warfarin, thereby providing insights into potential risks and implications. In order to address the research question “What potential drug in‑ teractions may arise when food supplements are taken concomitantly with warfarin?”, a PRISMA 2020 systematic review was conducted. To accomplish a comprehensive under‑ standing of the issue at hand, several databases were consulted. In order to fulfill the search platforms’ requirements, the terms “interactions”, “warfarin”, and “supplements” were combined in multiple ways. The inclusion criteria took into account original, ran‑ domized or non‑randomized studies and case studies that mention a supplement used concomitantly with warfarin. An artificial intelligence‑based tool was used to evaluate the studies’ quality. The obtained results were summarized in a table format, detailing the supplement used and the how the interaction occurs. A search of the literature yielded 968 articles, of which 14 were selected for review. These articles met the specified criteria, namely the use of a dietary supplement concomitantly with warfarin. Of these, 11 indicated a potential interaction, while three articles suggested that no interaction occurred. This work clarified the interactions between supplements and warfarin, emphasizing supplements such as dong quai, milk thistle, and American ginseng, which alter the mechanism of action of the drug. Furthermore, it is imperative for patients to seek counsel from healthcare professionals before modifying their dietary regimen.