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    Antioxidative Effects of Curcumin on Erastin-Induced Ferroptosis Through GPX4 Signalling
    (MDPI, 2025) Kose, T; Sharp, PA; Latunde-Dada, GO
    Background/Objectives: Pancreatic cancer is a common gastrointestinal cancer with high risk of mortality. Currently, the therapeutic strategies for pancreatic cancers are surgery, chemotherapy, and radiotherapy, none of which are effective treatments. Ferroptosis is a new form of cell death that is iron (Fe)-dependent and characterized by lipid peroxidation, which is a new approach for treatment of pancreatic cancer. Therefore, this study was dedicated to investigating the effect of erastin and Ras-selective lethal small molecule 3 (RLS3) as ferroptosis inducers as well as focusing on the antioxidant effects of two natural products, curcumin and (-)-epigallocatechin-3-gallate (EGCG), against ferroptosis. Methods: PANC1 cells were treated with 20 mu mol/L curcumin or EGCG and then exposed to 20 mu mol/L erastin. Cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay, Reactive Oxygen Species (ROS) were measured by dihydrodichlorofluorescein (H2DCF) cell-permeant probe, Fe levels were determined by inductively coupled plasma mass spectrometry (ICP-MS), and glutathione (GSH), lipid peroxidation, Western blot, and mRNA were assayed with commercially available kits. Results: Curcumin and EGCG enhanced cell viability in erastin-treated PANC1 cells in a dose-and time-dependent manner. Erastin-treated PANC1 cells exhibited the elevated levels of GSH depletion, ROS productions, and lipid peroxidation while curcumin reversed the erastin-induced ferroptotic effects. The treatment of erastin-induced PANC1 cells with curcumin increased the GPX4 mRNA gene and protein levels. Also, curcumin decreased the FTH1 mRNA gene levels as a strong Fe chelator. Conclusions: In conclusion, this study shows that erastin can be potentially a therapeutic strategy for treatment of cancer cells. Additionally, curcumin might play an antioxidant role at the specific concentrations, potentially mitigating ferroptosis in cells.
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    Dietary hempseed and cardiovascular health: nutritional composition, mechanisms and comparison with other seeds
    (FRONTIERS MEDIA SA, 2025) Kaçar, ÖF; Kose, T; Kaçar, HK
    Cardiovascular disease (CVD) remains the leading cause of global mortality, with dietary habits playing a significant role in its prevention and management. Hempseed (Cannabis sativa L.) has gained recognition as a functional food due to its rich nutritional profile, including high-quality plant proteins, optimal omega-6 to omega-3 fatty acid ratios, and a variety of bioactive compounds such as tocopherols, phytosterols, and polyphenols. This review critically evaluates the potential cardioprotective effects of hempseed, focusing on its impact on lipid metabolism, inflammation, oxidative stress, and other cardiometabolic markers. Preclinical studies suggest that hempseed can improve lipid profiles, reduce blood pressure, and reduce oxidative stress and inflammation, though clinical evidence remains limited and findings from animal models may not directly translate to human cardiovascular benefits due to physiological differences between species. This review further evaluates hempseed's potential in cardiovascular disease prevention and highlights its potential advantages when compared with other widely consumed seeds (flaxseed and chia seeds), emphasizing its unique fatty acid composition, optimal omega-6 to omega-3 ratio, and diverse bioactive compounds. Despite the promising findings, there is a need for long-term randomized controlled trials to establish the efficacy and safety of hempseed in diverse populations. This review emphasizes the potential of hempseed as a dietary intervention for CVD prevention and calls for further research to optimize its use in clinical and public health settings.
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    Effect of histidine and carnosine on haemoglobin recovery in anaemia induced-kidney damage and iron-loading mouse models
    (SPRINGER WIEN, 2025) Vera-Aviles, M; Moreno-Fernandez, J; Kose, T; Hider, R; Latunde-Dada, GO
    Histidine and carnosine can form complexes with divalent metal ions such as Fe2+, potentially providing stability to intracellular labile iron. Anaemia is a common comorbidity in the late stages of kidney disease, and patients are treated with erythropoiesis-stimulating agents (ESAs) and iron supplementation. However, iron supplementation is also associated with worse long-term outcomes. The purpose of this study is to investigate how histidine and carnosine supplementation can reduce symptoms of anaemia of chronic kidney disease (CKD) and the effects associated with iron-overloaded conditions. Adenine-induced chronic kidney disease mice were treated with histidine and carnosine by oral gavage for 10 days. Additionally, a model involving iron overload in mice was established, and these mice received concurrent treatment with histidine and carnosine. Haemoglobin, non-haem iron, malondialdehyde (MDA) and iron parameters were measured. Carnosine increased erythropoietin (EPO) levels (35.62 mu g/ml +/- 11.43) and resulted in haemoglobin repletion (16.7 g/dL +/- 3.4). When iron was supplemented alongside with histidine or carnosine, there were better effects on haemoglobin repletion (14.22 +/- 1.7 and 13.82 +/- 2.15 g/ dL respectively), ferritin (59.5 +/- 16.4, 52 +/- 29.5 mu g/ml) and non-haem iron (0.8 +/- 0.21, 0.7 +/- 0.38 nmol/mg), than the group receiving iron alone (p < 0.05). Furthermore, histidine and carnosine reduced non-haem iron and MDA, in iron-loaded conditions (p < 0.05). These positive effects observed in histidine and carnosine could be associated with reactive oxygen species (ROS) scavenging. EPO restoring levels in CKD model and the increment in haemoglobin and ferritin in carnosine treatments suggested the potential formation of a ternary complex with iron-glutathione. In conclusion, our results indicate the beneficial effect of histidine and carnosine in the context of iron supplementation for the correction of haemoglobin and protection against iron-loaded conditions.
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    The effect of fortification on in vitro iron and zinc bioavailability in plant-based meat alternatives
    (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2025) Kose, T; de Bie, T; Wang, RZ; Eilander, A; Wanders, A; Sharp, PA
    Plant-based diets are increasingly popular due to their perceived health benefits and positive environmental impact. However, there are concerns that long-term adherence to plant-based diets could result in nutritional deficiencies, especially for minerals found in abundance in animal foods. Therefore, plant-based meat substitutes may be a vehicle for fortification to provide a source of bioavailable minerals. This study investigated the iron (Fe), zinc (Zn) and calcium (Ca) content and bioavailability from unfortified and Fe and/or Zn fortified plant-based mince (PBM) compared with animal mince. Total and bioaccessible mineral levels in animal mince, and PBM were determined using microwave digestion and in vitro simulated gastrointestinal digestion, respectively. Mineral bioavailability was assessed by exposure of Caco-2 cells to the digested food samples and measuring mineral uptake into the cells using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Total phytate levels were measured to calculate the phytic acid:mineral molar ratio (PA:Fe, PA:Zn, PA:Ca) as indication of the mineral bioavailability. Fe bioavailability from animal mince was significantly greater than from unfortified PBM. Fortification of PBM with Fe reduced the PA:Fe molar ratio to below 10, and increased Fe bioavailability compared with the unfortified PBM. Total Fe uptake from fortified PBM was equivalent to that from animal mince. Following fortification of PBM with Zn, the PA:Zn ratio remained high (>14), and bioavailability was not enhanced compared with the unfortified PBM (P > 0.1). This study highlights that Fe-fortified PBM can improve Fe bioavailability and provide similar amounts of Fe compared to beef mince, whereas more research is needed for Zn fortification of PBM. Fortification can be a promising approach to reduce the phytic acid:mineral molar ratio to mitigate the inhibitory effect of PA on mineral bioavailability.