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Antioxidants, Volume 14, Issue 2 (February 2025) – 70 articles

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18 pages, 7346 KiB  
Article
Osteosarcoma Cells and Undifferentiated Human Mesenchymal Stromal Cells Are More Susceptible to Ferroptosis than Differentiated Human Mesenchymal Stromal Cells
by Yuliya D. Smirnova, Dominik Hanetseder, Lukas Derigo, Andreas Sebastian Gasser, Annette Vaglio-Garro, Simon Sperger, Regina Brunauer, Olga S. Korneeva, Johanna Catharina Duvigneau, Darja Marolt Presen and Andrey V. Kozlov
Antioxidants 2025, 14(2), 189; https://doi.org/10.3390/antiox14020189 - 6 Feb 2025
Abstract
Current research suggests that promoting ferroptosis, a non-apoptotic form of cell death, may be an effective therapy for osteosarcoma, while its inhibition could facilitate bone regeneration and prevent osteoporosis. Our objective was to investigate whether the susceptibility to and regulation of ferroptosis differ [...] Read more.
Current research suggests that promoting ferroptosis, a non-apoptotic form of cell death, may be an effective therapy for osteosarcoma, while its inhibition could facilitate bone regeneration and prevent osteoporosis. Our objective was to investigate whether the susceptibility to and regulation of ferroptosis differ between undifferentiated (UBC) and differentiated (DBC) human bone marrow stromal cells, as well as human osteosarcoma cells (MG63). Ferroptosis was induced by either inhibiting glutathione peroxidase 4 (GPX4) using RSL3 or blocking all glutathione-dependent enzymes through inhibition of the glutamate/cysteine antiporter with Erastin. Lipid peroxidation was assessed using the fluorescent probe BODIPY™581/591C11, while Ferrostatin-1 was used to inhibit ferroptosis. We demonstrate that neither Erastin nor RSL3 induces ferroptosis in DBC. However, both RSL3 and Erastin induce ferroptosis in UBC, while Erastin predominantly induces ferroptosis in MG63 cells. Our data suggest that ferroptosis induction in undifferentiated hBMSCs is primarily regulated by GPX4, whereas glutathione S-Transferase P1 (GSTP1) plays a key role in controlling ferroptosis in osteosarcoma cells. In conclusion, targeting the key pathways involved in ferroptosis across different bone cell types may improve the efficacy of cancer treatments while minimizing collateral damage and supporting regenerative processes, with minimal impact on cancer therapy. Full article
(This article belongs to the Section Aberrant Oxidation of Biomolecules)
13 pages, 559 KiB  
Article
(Poly)phenols and Multiple Sclerosis: Results from an Observational Cross-Sectional Study
by Monica Guglielmetti, Cinzia Ferraris, Anna Tagliabue, Evelyn Frias-Toral, Eleonora Tavazzi, Alessandro La Malfa, Giacomo Greco, Roberto Bergamaschi, Raynier Zambrano-Villacres, Justyna Godos and Giuseppe Grosso
Antioxidants 2025, 14(2), 188; https://doi.org/10.3390/antiox14020188 - 6 Feb 2025
Viewed by 101
Abstract
(Poly)phenols are a wide and heterogeneous class of substances with several potential health benefits. Their role in neuroprotection and cognition is still questionable. This study’s scope is to examine the possible association between total and individual (poly)phenol intake, major dietary sources, and the [...] Read more.
(Poly)phenols are a wide and heterogeneous class of substances with several potential health benefits. Their role in neuroprotection and cognition is still questionable. This study’s scope is to examine the possible association between total and individual (poly)phenol intake, major dietary sources, and the severity of multiple sclerosis (MS) in a cohort of MS patients. Participants’ demographics, physical activity, smoking, and dietary information were collected, alongside clinical parameters including the Expanded Disability Status Score (EDSS), Multiple Sclerosis Severity Score (MSSS), MS phenotype, and current therapy. A validated 110-item food frequency questionnaire (FFQ) was used to assess participants’ habits. The (poly)phenol content of foods was estimated using the Phenol-Explorer database. Data from 106 participants were analyzed. A high intake of vegetables was associated with a 4.6-fold higher probability of mild MS (95% CI: 1.49, 14.28), whereas no association was found for other food and beverage sources. Hydroxycinnamic acids were significantly related to MSSS (OR: 6.55, 95% CI: 2.15, 19.92). Although coffee intake differed significantly between patients with mild and severe MS (90.5 ± 53.9 vs. 59.4 ± 40.8 mL/d, respectively), linear regression analysis did not confirm an association with MSSS. A higher intake of hydroxycinnamic acids and vegetables may impact MS severity. Coffee’s role remains unclear and needs to be further investigated. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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25 pages, 775 KiB  
Review
The Heme Oxygenase/Biliverdin Reductase System and Its Genetic Variants in Physiology and Diseases
by Cesare Mancuso
Antioxidants 2025, 14(2), 187; https://doi.org/10.3390/antiox14020187 - 6 Feb 2025
Viewed by 167
Abstract
Heme oxygenase (HO) metabolizes heme into ferrous iron, carbon monoxide (CO), and biliverdin-IXα (BV), the latter being reduced into bilirubin-IXα (BR) by the biliverdin reductase-A (BVR). Heme oxygenase exists as two isoforms, HO-1, inducible and involved in the cell stress response, and HO-2, [...] Read more.
Heme oxygenase (HO) metabolizes heme into ferrous iron, carbon monoxide (CO), and biliverdin-IXα (BV), the latter being reduced into bilirubin-IXα (BR) by the biliverdin reductase-A (BVR). Heme oxygenase exists as two isoforms, HO-1, inducible and involved in the cell stress response, and HO-2, constitutive and committed to the physiologic turnover of heme and in the intracellular oxygen sensing. Many studies have identified genetic variants of the HO/BVR system and suggested their connection in free radical-induced diseases. The most common genetic variants include (GT)n dinucleotide length polymorphisms and single nucleotide polymorphisms. Gain-of-function mutations in the HO-1 and HO-2 genes foster the ventilator response to hypoxia and reduce the risk of coronary heart disease and age-related macular degeneration but increase the risk of neonatal jaundice, sickle cell disease, and Parkinson’s disease. Conversely, loss-of-function mutations in the HO-1 gene increase the risk of type 2 diabetes mellitus, chronic obstructive pulmonary disease, and some types of cancers. Regarding BVR, the reported loss-of-function mutations increase the risk of green jaundice. Unfortunately, the physiological role of the HO/BVR system does not allow for the hypothesis gene silencing/induction strategies, but knowledge of these mutations can certainly facilitate a medical approach that enables early diagnoses and tailored treatments. Full article
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21 pages, 5783 KiB  
Article
Gossypin-Loaded Ethosome Gel for Cutaneous Administration: A Preliminary Study on Melanoma Cells
by Agnese Bondi, Walter Pula, Mascia Benedusi, Giulia Trinchera, Anna Baldisserotto, Stefano Manfredini, Maria Grazia Ortore, Alessia Pepe, Paolo Mariani, Marc C. A. Stuart, Giuseppe Valacchi and Elisabetta Esposito
Antioxidants 2025, 14(2), 186; https://doi.org/10.3390/antiox14020186 - 5 Feb 2025
Viewed by 238
Abstract
A preformulative study was conducted to produce and characterize ethosomes for the transdermal delivery of gossypin. This plant-derived compound possesses many pharmacological properties, including antitumoral potential. Ethosome dispersions were designed as transdermal delivery systems for gossypin, employing two different production procedures. The evaluation [...] Read more.
A preformulative study was conducted to produce and characterize ethosomes for the transdermal delivery of gossypin. This plant-derived compound possesses many pharmacological properties, including antitumoral potential. Ethosome dispersions were designed as transdermal delivery systems for gossypin, employing two different production procedures. The evaluation of vesicle size distribution by photon correlation spectroscopy, morphology by cryogenic transmission electron microscopy, and gossypin entrapment capacity, as well as in vitro release and permeation by vertical diffusion cells, enabled us to select a production strategy based on the injection of a phosphatidylcholine ethanolic solution in water. Indeed, vesicles prepared by this method were almost unilamellar and measured roughly 150 nm mean diameter while displaying an entrapment capacity higher than 94%. Moreover, vesicles prepared by the ethanol injection method enabled us to control gossypin release and to improve its permeation with respect to the solution of the drug. To obtain semi-solid forms suitable for cutaneous gossypin administration, ethosome dispersions were thickened with 0.5% w/w xanthan gum, selected by a spreadability test. These ethosome gels were then further characterized by small- and wide-angle X-ray scattering, while their antioxidant activity was demonstrated in vitro by a radical scavenging assay. Finally, in vitro biological studies were conducted on A375 melanoma cell lines. Namely, wound healing and cell migration assays confirmed the potential antitumoral effect of gossypin, especially when loaded in the selected ethosomal gel. The promising results suggest further investigation of the potential of gossypin-loaded ethosomal gel in the treatment of melanoma. Full article
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4 pages, 151 KiB  
Editorial
Natural Antioxidants and Aquatic Animal Health
by Rui Jia
Antioxidants 2025, 14(2), 185; https://doi.org/10.3390/antiox14020185 - 5 Feb 2025
Viewed by 155
Abstract
In intensive aquaculture, aquatic animals inevitably encounter multiple stressors due to environmental fluctuations, triggering various stress responses, with oxidative stress being the most prevalent [...] Full article
(This article belongs to the Special Issue Natural Antioxidants and Aquatic Animal Health)
17 pages, 289 KiB  
Article
Fetal Growth Is Associated with Amniotic Fluid Antioxidant Capacity, Oxidative Stress, Minerals and Prenatal Supplementation: A Retrospective Study
by Mozhgan Kohzadi, Stan Kubow and Kristine G. Koski
Antioxidants 2025, 14(2), 184; https://doi.org/10.3390/antiox14020184 - 5 Feb 2025
Viewed by 238
Abstract
Background: Associations of antioxidants in prenatal over-the-counter multivitamin-mineral (OTC MVM) supplements with in-utero oxidative stress (OS), antioxidant capacity, and fetal growth are limited. Our objectives were to determine if five fetal ultrasound measurements [biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur [...] Read more.
Background: Associations of antioxidants in prenatal over-the-counter multivitamin-mineral (OTC MVM) supplements with in-utero oxidative stress (OS), antioxidant capacity, and fetal growth are limited. Our objectives were to determine if five fetal ultrasound measurements [biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), and estimated fetal weight] were associated with OTC MVM supplements and with minerals, biomarkers of OS, and total antioxidant capacity in amniotic fluid (AF). Methods: For this retrospective study, 176 pregnant women who had undergone age-related amniocentesis for genetic testing were included. Questionnaires recorded prenatal OTC MVM supplementation (yes, no). Ultrasound measurements for early (16–20 weeks) and late (32–36 weeks) gestation were extracted from medical charts. AF concentrations for 15 minerals and trace elements and OS biomarkers in AF [nitric oxide (NO), thiobarbituric acid-reactive substances (TBARS), and ferric-reducing antioxidant power (FRAP)] were measured at 12–20 weeks of gestation. Associations of AF minerals, OS biomarkers, and ultrasound measures were analyzed using multiple linear regressions. Results: Positive associations were observed between AF TBARS and seven AF minerals/elements (calcium, copper, magnesium, nickel, strontium, zinc and iron). At 16–20 weeks, AF copper, nickel, strontium, and selenium were positively associated with BPD, HC, AC, and FL, respectively, NO was positively associated with FL, and FRAP was inversely associated with estimated weight. At 32–36 weeks, calcium was positively associated with BPD and chromium and arsenic were negatively with HC. At 16–20 weeks, higher AF FRAP was inversely associated with FL and this exposure continued to be inversely associated with estimated weight at 32–36 weeks. Conclusions: Concentrations of AF minerals, trace elements and biomarkers of OS and in-utero antioxidant capacity were linked to specific ultrasound measurements at different stages of gestation, suggesting a complex interplay among in utero OS, antioxidant capacity, OTC MVM supplements, and fetal growth. Full article
(This article belongs to the Special Issue Oxidative Stress in Reproduction of Mammals)
41 pages, 5000 KiB  
Review
Transcription Factor Blimp-1: A Central Regulator of Oxidative Stress and Metabolic Reprogramming in Chronic Inflammatory Diseases
by Aline Yen Ling Wang, Ana Elena Aviña, Yen-Yu Liu, Yun-Ching Chang and Huang-Kai Kao
Antioxidants 2025, 14(2), 183; https://doi.org/10.3390/antiox14020183 - 4 Feb 2025
Viewed by 373
Abstract
B-lymphocyte-induced maturation protein 1 (Blimp-1) is a transcription factor that, among other functions, modulates metabolism and helps to regulate antioxidant pathways, which is important in the context of chronic inflammatory diseases like diabetes, cardiovascular disease, and autoimmune disease. In immune cell function, Blimp-1 [...] Read more.
B-lymphocyte-induced maturation protein 1 (Blimp-1) is a transcription factor that, among other functions, modulates metabolism and helps to regulate antioxidant pathways, which is important in the context of chronic inflammatory diseases like diabetes, cardiovascular disease, and autoimmune disease. In immune cell function, Blimp-1 has a modulatory role in the orchestration of metabolic reprogramming and as a promoter of anti-inflammatory cytokines, including IL-10, responsible for modulating oxidative stress and immune homeostasis. Moreover, Blimp-1 also modulates key metabolic aspects, such as glycolysis and fatty acid oxidation, which regulate reactive oxygen species levels, as well as tissue protection. This review depicts Blimp-1 as an important regulator of antioxidant defenses and anti-inflammation and suggests that the protein could serve as a therapeutic target in chronic inflammatory and metabolic dysregulation conditions. The modulation of Blimp-1 in diseases such as diabetic coronary heart disease and atherosclerosis could alleviate oxidative stress, augment the protection of tissues, and improve disease outcomes. The therapeutic potential for the development of new treatments for these chronic conditions lies in the synergy between the regulation of Blimp-1 and antioxidant therapies, which are future directions that may be pursued. This review emphasizes Blimp-1’s emerging importance as a novel regulator in the pathogenesis of inflammatory diseases, providing new opportunities for therapeutic intervention. Full article
(This article belongs to the Special Issue Oxidative Stress in Chronic Diseases: A Focus on Rheumatoid Arthritis)
18 pages, 4044 KiB  
Article
The Effects of Fisetin on Gene Expression Profile and Cellular Metabolism in IFN-γ-Stimulated Macrophage Inflammation
by Ziyu He, Xuchi Pan, Kun Xie, Kozue Sakao, Jihua Chen, Masaharu Komatsu and De-Xing Hou
Antioxidants 2025, 14(2), 182; https://doi.org/10.3390/antiox14020182 - 4 Feb 2025
Viewed by 357
Abstract
Although interferon-gamma (IFN-γ) is known as a critical factor in polarizing macrophages into the pro-inflammatory state for immune response, how dietary flavonoids regulate IFN-γ response for anti-inflammation is incompletely elucidated. This study aims to investigate the effect of fisetin, a typical flavonol, on [...] Read more.
Although interferon-gamma (IFN-γ) is known as a critical factor in polarizing macrophages into the pro-inflammatory state for immune response, how dietary flavonoids regulate IFN-γ response for anti-inflammation is incompletely elucidated. This study aims to investigate the effect of fisetin, a typical flavonol, on the inhibition of IFN-γ-induced inflammation by RNA sequencing (RNA-Seq) and cellular metabolism analysis. RAW264 macrophages pretreated with fisetin following IFN-γ stimulation were subjected to RNA-Seq to analyze alterations in gene expression. Cellular signaling and transcription were investigated using enrichment analysis, motif analysis, and transcription factor prediction. Cellular metabolic state was assessed by measuring the oxygen consumption rate (OCR) and lactate level to reflect mitochondrial respiration and glycolysis. Alterations in signaling proteins were confirmed by Western blot. The results revealed that fisetin downregulated the IFN-γ-induced expression of pro-inflammatory genes and M1 marker genes such as Cxcl9, Il6, Cd80, Cd86, and Nos2. In cellular metabolism, fisetin upregulated the oxidative phosphorylation (OXPHOS) pathway, restored impaired OCR, and reduced lactate production induced by IFN-γ. Motif analysis suggested that fisetin suppressed the activation of IFN-regulatory factor 1 (IRF1). Western blot data further confirmed that fisetin inhibited the phosphorylation of Jak1, Jak2, and STAT1, and decreased the nuclear accumulation of phosphorylated STAT1 and IRF1 induced by IFN-γ. Taken together, our data revealed that fisetin is a potent flavonoid that attenuates IFN-γ-stimulated murine macrophage inflammation and ameliorates disrupted cellular metabolism with a possible Jak1/2-STAT1-IRF1 pathway. Full article
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22 pages, 1335 KiB  
Article
Exploring the Epicarp Potential from Acrocomia aculeata Fruits: Chemical Analysis, Antioxidant and Antimicrobial Activities
by Fabiane da Conceição Vieira Santos, Gabriel Rocha Martins, Sandra Regina da Silva Luiz, Isadora de Araújo Oliveira, Leandro Pereira da Silva, Antonio Jorge Ribeiro da Silva, Marcos Dias Pereira, Rosana Conrado Lopes, Celuta Sales Alviano and Daniela Sales Alviano Moreno
Antioxidants 2025, 14(2), 181; https://doi.org/10.3390/antiox14020181 - 4 Feb 2025
Viewed by 410
Abstract
The interest in new sources of bioactive compounds has been driven by the search for natural antioxidants capable of attenuating the toxicity of reactive oxygen species, as well as the emergence of pathogens resistant to antimicrobials. In this sense, we explored the potential [...] Read more.
The interest in new sources of bioactive compounds has been driven by the search for natural antioxidants capable of attenuating the toxicity of reactive oxygen species, as well as the emergence of pathogens resistant to antimicrobials. In this sense, we explored the potential of the macaúba epicarp. Compounds such as piceatannol, 3,4,5,3′,5′-penta-hydroxy-trans-stilbene (PHS), and in lower amounts, resveratrol were identified in extracts through techniques such as medium-pressure liquid chromatography, HPLC-MS, and imaging mass spectrometry (IMS), which confirmed the exclusive localization of PHS and piceatannol in the outer epicarp. Extraction with aqueous acetone (Me2CO:H2O) and its EtOAC fraction showed the highest yields of stilbenes and, moreover, it efficiently increased the tolerance of Saccharomyces cerevisiae to oxidative stress. Additionally, the Me2CO:H2O extract presented antibacterial and anti-cryptococcal activity, with piceatannol and resveratrol increasing survival rates of Galleria mellonella subjected to fungal infection. In silico ADMET (absorption, distribution, metabolism, excretion and toxicity) analysis indicates low toxicity for piceatannol, PHS, and resveratrol, in addition to pharmacokinetic parameters that allow their use. These findings indicate the use of macaúba epicarp as a source of bioactive compounds valuable for the food, cosmetic, and pharmaceutical industries. Full article
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14 pages, 1023 KiB  
Article
Evidence for a Functional Link Between the Nrf2 Signalling Pathway and Cytoprotective Effect of S-Petasin in Human Retinal Pigment Epithelium Cells Exposed to Oxidative Stress
by Michela Pizzoferrato, Giacomo Lazzarino, Anna Brancato, Elisabetta Tabolacci, Maria Elisabetta Clementi and Giuseppe Tringali
Antioxidants 2025, 14(2), 180; https://doi.org/10.3390/antiox14020180 - 4 Feb 2025
Viewed by 418
Abstract
The retinal pigment epithelium (RPE) is a highly specialised monolayer epithelium subjected to constant oxidative stress, which, in the long term, favours the development of a complex pathological process that is the underlying cause of macular damage. Therefore, counteracting the overproduction of ROS [...] Read more.
The retinal pigment epithelium (RPE) is a highly specialised monolayer epithelium subjected to constant oxidative stress, which, in the long term, favours the development of a complex pathological process that is the underlying cause of macular damage. Therefore, counteracting the overproduction of ROS is the best-researched approach to preserve the functional integrity of the RPE. S-Petasin, a secondary metabolite extracted from the plant Petasites hybridus, has numerous biological effects, which highlight its anti-inflammatory and antioxidative properties. The aim of our study is to investigate whether S-Petasin exerts cytoprotective effects by protecting the RPE from oxidative damage. The effects of pretreatment with S-Petasin were assessed by the determination of the cell viability, intracellular ROS levels, activation of the Nrf2 pathway and the resulting post-transcriptional antioxidant/antiapoptotic response. Our results show that S-Petasin pretreatment (1) reduces intracellular ROS levels, improving cell viability of RPE exposed to oxidative damage; (2) activates the Nrf2 signalling pathway, modulating the post-transcriptional response of its antioxidant chemical biomarkers; (3) reduces the Bax levels, and an increase in those of Bcl-2, with a concomitant downregulation of the Bax/Bc-2 ratio. Overall, our results provide the first evidence that S-Petasin is able to protect the RPE from oxidative damage. Full article
(This article belongs to the Special Issue Oxidative Stress and NRF2 in Health and Disease—2nd Edition)
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14 pages, 1694 KiB  
Article
The Influence of 2.45 GHz Wi-Fi Exposure Duration on Sperm Quality and Testicular Histopathology: An Exploration of Peroxidative Injury
by Norazurashima Jamaludin, Siti Fatimah Ibrahim, Farah Hanan Fathihah Jaffar, Aini Farzana Zulkefli and Khairul Osman
Antioxidants 2025, 14(2), 179; https://doi.org/10.3390/antiox14020179 - 4 Feb 2025
Viewed by 402
Abstract
Concerns have arisen about the impact of wireless technology on male fertility, particularly regarding the duration of 2.45 GHz Wi-Fi radiation exposure. This study examines the influence of various exposure durations on sperm parameters and testicular histopathology, focusing on malondialdehyde as an oxidative [...] Read more.
Concerns have arisen about the impact of wireless technology on male fertility, particularly regarding the duration of 2.45 GHz Wi-Fi radiation exposure. This study examines the influence of various exposure durations on sperm parameters and testicular histopathology, focusing on malondialdehyde as an oxidative stress marker. Twenty-four Sprague Dawley rats were exposed for eight weeks, after which their sperm concentration, motility, and viability and testicular histopathology were assessed. Malondialdehyde levels were measured using an Enzyme-Linked Immunosorbent Assay. One-way ANOVAs with Tukey’s post hoc tests were conducted for the sperm concentration, motility, and viability; the seminiferous epithelium height; and malondialdehyde. The Kruskal–Wallis H test was used for the Johnsen Score and seminiferous tubule diameter. The results indicated that 4 h of exposure to 2.45 GHz radiation induced oxidative stress and adversely affected sperm parameters and the testicular ultrastructure. Gradual recovery was observed at 8 h, with further improvement at 24 h, suggesting the activation of cell repair mechanisms. This was supported by significant changes in testicular organ coefficients, indicating potential recovery. Our findings suggest that Wi-Fi exposure reduces sperm fertility potential, with the body showing limited capacity for complete recovery from the damage. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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27 pages, 3854 KiB  
Article
Oxidative Score and Microvesicle Profile Suggest Cardiovascular Risk in Chronic Kidney Disease
by Gemma Valera-Arévalo, María del Mar Rodríguez-San Pedro, Paula Jara Caro, Víctor Cabanillas, María Gabriela Ortiz-Diaz, Andrea Figuer, Claudia Yuste, Rafael Ramírez, Matilde Alique, Enrique Morales, Natalia Guerra-Pérez and Julia Carracedo
Antioxidants 2025, 14(2), 178; https://doi.org/10.3390/antiox14020178 - 3 Feb 2025
Viewed by 413
Abstract
Chronic kidney disease (CKD) is associated with a high incidence of cardiovascular disease (CVD) due to the accumulation of uremic toxins, altered redox state, and chronic systemic inflammation. This study aimed to analyze the relationship between the redox status of patients with CKD [...] Read more.
Chronic kidney disease (CKD) is associated with a high incidence of cardiovascular disease (CVD) due to the accumulation of uremic toxins, altered redox state, and chronic systemic inflammation. This study aimed to analyze the relationship between the redox status of patients with CKD and the phenotype of microvesicles (MVs) subtypes, and cardiovascular events. The oxidative stress level of each participant was determined using an individualized OXY-SCORE. The relationship between pro-oxidant and antioxidant parameters and the expression of membrane markers in endothelial-derived microvesicles (EMVs) and platelet-derived microvesicles (PMVs) was established. Patients with advanced CKD (ACKD) and hemodialysis (HD) had a higher OXY-SCORE than healthy subjects (HS), whereas peritoneal dialysis (PD) patients had similar scores to HS. PD patients showed elevated PMVs and CD41 expression, whereas HD patients had higher EMVs and CD31 expression. Patients with ACKD had higher tissue factor (TF) expression in the PMVs and EMVs. TF expression was correlated with xanthine oxidase (XO) activity and was negatively correlated with antioxidant parameters. Patients with cardiovascular events show elevated TF. In conclusion, microvesicles and oxidative stress may serve as markers of cardiovascular risk in CKD, with TF expression in PMVs and EMVs being potential predictive and prognostic biomarkers of CVD. Full article
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23 pages, 2670 KiB  
Review
The Role of Extracellular Vesicles in Aging and Age-Related Disorders
by Bharathi Hassan Ganesh, Himabindu Padinjarathil, Ramya Lakshmi Rajendran, Prasanna Ramani, Prakash Gangadaran and Byeong-Cheol Ahn
Antioxidants 2025, 14(2), 177; https://doi.org/10.3390/antiox14020177 - 3 Feb 2025
Viewed by 462
Abstract
A variety of molecular and cellular changes distinguish the multifaceted biological process of aging. Recent studies in this decade have demonstrated the essential role of extracellular vesicles (EVs) in the aging process. Mitochondrial malfunction and increased oxidative stress are major contributors for the [...] Read more.
A variety of molecular and cellular changes distinguish the multifaceted biological process of aging. Recent studies in this decade have demonstrated the essential role of extracellular vesicles (EVs) in the aging process. Mitochondrial malfunction and increased oxidative stress are major contributors for the aging process. This review investigates the role of EVs in intercellular communication, tissue regeneration, and inflammation in the context of aging. We also discuss the exosome and its utility to reduce oxidative stress, which is a key part of aging, as well as the possibility of using the exosomes (EVs) as anti-aging drugs. Changes in cargo composition can influence the aging phenotype and impact the functionality of cells and tissues. Additionally, the role of EVs in oxidative stress during the aging process addresses potential treatment strategies and the development of biomarkers for age-associated disorders. The review also highlighted the role of exosomes in providing antioxidant properties, which help reduce excessive reactive oxygen species (ROS) and strengthen cellular defenses against oxidative stress. Additionally, it emphasized the role of extracellular vesicles (EVs) in age-related pathologies, such as neurodegenerative diseases, cardiovascular disorders, and immunosenescence, offering insights into targeted interventions for promoting healthy aging. This article provides a comprehensive analysis of the current body of knowledge regarding the therapeutic effects of EVs on aging, with a particular emphasis on the implications of this emerging field of research and its relationship to oxidative stress. Full article
(This article belongs to the Special Issue The OxInflammation Process and Tissue Repair)
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12 pages, 3043 KiB  
Article
Analysis of Singlet Oxygen Luminescence Generated By Protoporphyrin IX
by Vikas Vikas, Weibing Yang, Brian C. Wilson, Timothy C. Zhu and Robert H. Hadfield
Antioxidants 2025, 14(2), 176; https://doi.org/10.3390/antiox14020176 - 31 Jan 2025
Viewed by 583
Abstract
The effectiveness of photodynamic therapy (PDT) for cancer treatment relies on the generation of cytotoxic singlet oxygen (1O2) in type II PDT. Hence, monitoring of 1O2 generation during PDT enables optimal treatment delivery to the tumor target [...] Read more.
The effectiveness of photodynamic therapy (PDT) for cancer treatment relies on the generation of cytotoxic singlet oxygen (1O2) in type II PDT. Hence, monitoring of 1O2 generation during PDT enables optimal treatment delivery to the tumor target with reduced off-target effects. Direct 1O2 observation by measuring its luminescence at 1270 nm remains challenging due to the very weak signal. This study presents 1O2 luminescence measurements using a time-resolved singlet oxygen luminescence detection system (TSOLD) applied to protoporphyrin IX (PpIX) in different solvents (ethanol and acetone) and biological media (bovine serum albumin and agarose-based solid phantom). The compact experimental setup includes a nanosecond diode laser with a function generator, a cuvette with photosensitizer solution, optical filtering and mirrors, an InGaAs single-photon avalanche diode detector, and time-tagger electronics. Increasing the concentration of PpIX in these media from 1 to 10 µg/g resulted in a 3–5 × increase in the 1O2 luminescence signal. Furthermore, increasing light scattering in the sample using Intralipid from 0.1 to 1% led to a decrease in the 1O2 luminescence signal and lifetime. These results confirm the marked effect of the microenvironment on the 1O2 signal and, hence, on the photodynamic efficacy. Full article
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24 pages, 11816 KiB  
Article
Coffee Compounds Protection Against Lipotoxicity Is Associated with Lipid Droplet Formation and Antioxidant Response in Primary Rat Hepatocytes
by Johanna C. Arroyave-Ospina, Magnolia Martínez, Manon Buist-Homan, Victoria Palasantzas, Marco Arrese and Han Moshage
Antioxidants 2025, 14(2), 175; https://doi.org/10.3390/antiox14020175 - 31 Jan 2025
Viewed by 507
Abstract
Metabolic dysfunction associated with steatotic liver disease (MASLD) is the result of disturbed lipid metabolism. In MASLD, the accumulation of free fatty acids (FFAs) in hepatocytes causes lipotoxicity mediated by oxidative stress. Coffee compounds are known for their beneficial effects in MASLD; however, [...] Read more.
Metabolic dysfunction associated with steatotic liver disease (MASLD) is the result of disturbed lipid metabolism. In MASLD, the accumulation of free fatty acids (FFAs) in hepatocytes causes lipotoxicity mediated by oxidative stress. Coffee compounds are known for their beneficial effects in MASLD; however, the mechanisms still need to be further explored. The aim of this study was to elucidate the protective mechanisms of coffee compounds against palmitate-induced lipotoxicity in primary hepatocytes. Methods: Primary hepatocytes were isolated from male Wistar rats and treated with palmitate (1 mmol/L) in combination with caffeine (CF: 1 mmol/L) or chlorogenic acid (CGA: 5 µmol/L). Mitochondrial ROS production, palmitate-induced necrosis, antioxidant response, ER stress markers and lipid droplet (LD) formation were assessed. Monoacylglycerols 2-SG (2-Stearolylglycerol), 2-OG (2-Oleoylglycerol) and SCD-1 (Stearoyl-CoA Desaturase 1) inhibitors were used to modulate LD formation. LD formation in steatotic Zucker rat hepatocytes was also investigated. Results: CF and CGA prevented palmitate-induced cell death and reduced ROS production. CF and CGA induced the antioxidant response, especially HO-1 expression, but had no significant effect on ER stress markers. CF and CGA increased LD formation in palmitate-treated cells. This effect was significantly reduced by 2-SG and SCD-1 inhibitors but enhanced by 2-OG. Lipid droplets were associated with lower palmitate toxicity and reduced ROS production. Conclusions: CF and CGA protect hepatocytes from lipotoxicity via modulation of the antioxidant response and enhance lipid droplet formation via an SCD-1-dependent mechanism. Oxidative stress-related toxicity in hepatocytes can be prevented by enhancing LD formation. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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25 pages, 18944 KiB  
Article
Effects of Black Cumin Seed Extract on Pancreatic Islet β-Cell Proliferation and Hypoglycemic Activity in Streptozotocin-Induced Diabetic Rats
by Jongkyu Kim, Yoon-Seok Chun, Namkyu Yoon, Byungkwon Kim, Kiin Choi, Sae-Kwang Ku and Namju Lee
Antioxidants 2025, 14(2), 174; https://doi.org/10.3390/antiox14020174 - 31 Jan 2025
Viewed by 484
Abstract
Thymoquinone (TQ), a bioactive compound derived from black cumin seeds, is renowned for its potent anti-obesity and anti-diabetic properties. Due to the stability challenges of TQ, it has predominantly been utilized in oil formulations. This study aimed to enhance the stability of TQ [...] Read more.
Thymoquinone (TQ), a bioactive compound derived from black cumin seeds, is renowned for its potent anti-obesity and anti-diabetic properties. Due to the stability challenges of TQ, it has predominantly been utilized in oil formulations. This study aimed to enhance the stability of TQ and investigated the impact of consuming insoluble fiber from black cumin seeds on restoring antioxidant function compromised by diabetes and improving hyperglycemia management. We evaluated the restorative effects of a 35-day administration of black cumin seed extract (BCS) on antioxidant function impaired by streptozotocin (STZ)-induced diabetes, alongside structural and functional alterations in the pancreas, liver, and kidneys. The results demonstrated significant improvements in organ weight, particularly in pancreatic tissue. Moreover, BCS administration markedly suppressed the expression of key genes associated with pancreatic dysfunction and damage, including caspase-3, transforming growth factor-beta 1 (TGF-β1), and interleukin-1 beta (IL-1β). Through oral glucose tolerance tests (OGTTs), BCS was found to effectively regulate chronic hyperglycemia and exhibit potential for managing acute hyperglycemia. These findings suggest that BCS not only addresses both glycemic and non-glycemic complications of diabetes but also offers a safe, long-term solution. Consequently, BCS emerges as a promising therapeutic agent for hyperglycemia management, including in prediabetic stages. Full article
24 pages, 4300 KiB  
Article
Screening and Whole-Genome Analysis of Probiotic Lactic Acid Bacteria with Potential Antioxidants from Yak Milk and Dairy Products in the Qinghai–Tibet Plateau
by Diyan Wu, Haichuan Li, Xuan Wang, Runtong Chen, Di Gong, Danfeng Long, Xiaodan Huang, Zhenchuang Tang and Ying Zhang
Antioxidants 2025, 14(2), 173; https://doi.org/10.3390/antiox14020173 - 31 Jan 2025
Viewed by 520
Abstract
This study aimed to isolate lactic acid bacteria (LAB) with strong antioxidant activity and potential probiotic properties from yak milk and dairy products in the Qinghai–Tibet Plateau. Initial screening of the isolates was performed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay and a hydrogen [...] Read more.
This study aimed to isolate lactic acid bacteria (LAB) with strong antioxidant activity and potential probiotic properties from yak milk and dairy products in the Qinghai–Tibet Plateau. Initial screening of the isolates was performed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay and a hydrogen peroxide tolerance test. Subsequently, the antioxidant capacity of the isolates was assessed through five distinct assays: 2,2′-azino-bis (3-ethylbenzthiazoline)-6-sulfonic acid (ABTS) radical scavenging ability, superoxide anion radical scavenging ability, hydroxyl radical scavenging ability, a DPPH scavenging assay, and a reducing activity assay. The strains with the stronger antioxidant potential were then further evaluated for their probiotic properties. Whole-genome sequencing was conducted on Lactobacillus plantarum QL01. Among 1205 isolates, 9 strains exhibited potential antioxidant capabilities. Following probiotic property evaluation, QL01 was identified as a safe candidate due to its strong growth, strong adhesion ability, and resilience to acidic, bile, and simulated gastrointestinal conditions. Genome analysis revealed that most of QL01’s genes were involved in carbohydrate metabolism. Further examination of antibiotic resistance and virulence factors confirmed its safety, meanwhile genes linked to adhesion and stress responses underscored its probiotic potential. In conclusion, QL01, a strong antioxidant strain, was successfully isolated, and its probiotic potential was confirmed through comprehensive in vitro and genomic analyses. Full article
(This article belongs to the Section Natural and Synthetic Antioxidants)
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20 pages, 4227 KiB  
Article
PFKFB3 Connects Glycolytic Metabolism with Endothelial Dysfunction in Human and Rodent Obesity
by Robert K. Batori, Zsuzsanna Bordan, Caleb A. Padgett, Yuqing Huo, Feng Chen, Reem T. Atawia, Rudolf Lucas, Masuko Ushio-Fukai, Tohru Fukai, Eric J. Belin de Chantemele, David W. Stepp and David J. R. Fulton
Antioxidants 2025, 14(2), 172; https://doi.org/10.3390/antiox14020172 - 31 Jan 2025
Viewed by 401
Abstract
Obesity and type 2 diabetes (T2D) increase cardiovascular risk, largely due to altered metabolic state. An early consequence of T2D/obesity is the loss of endothelial function and impaired nitric oxide (NO) signaling. In blood vessels, endothelial nitric oxide synthase (eNOS) synthesizes NO to [...] Read more.
Obesity and type 2 diabetes (T2D) increase cardiovascular risk, largely due to altered metabolic state. An early consequence of T2D/obesity is the loss of endothelial function and impaired nitric oxide (NO) signaling. In blood vessels, endothelial nitric oxide synthase (eNOS) synthesizes NO to maintain vessel homeostasis. The biological actions of NO are compromised by superoxide that is generated by NADPH oxidases (NOXs). Herein we investigated how altered metabolism affects superoxide/NO balance in obesity. We found that eNOS expression and NO bioavailability are significantly decreased in endothelial cells (ECs) from T2D patients and animal models of obesity. In parallel, PFKFB3, a key glycolytic regulatory enzyme, is significantly increased in ECs of obese animals. EC overexpression of wild-type and a cytosol-restricted mutant PFKFB3 decreased NO production due to increased eNOS-T495 phosphorylation. PFKFB3 also blunted Akt-S473 phosphorylation, reducing stimulus-dependent phosphorylation of S1177 and the activation of eNOS. Furthermore, PFKFB3 enhanced the activities of NOX1 and NOX5, which are major contributors to endothelial dysfunction. Prolonged exposure of ECs to high glucose or TNFα, which are hallmarks of T2D, leads to increased PFKFB3 expression. These results demonstrate a novel functional relationship between endothelial metabolism, ROS, and NO balance that may contribute to endothelial dysfunction in obesity. Full article
(This article belongs to the Special Issue NADPH Oxidases (NOXs))
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20 pages, 10130 KiB  
Article
Extra Virgin Olive Oil Polyphenol-Enriched Extracts Exert Antioxidant and Anti-Inflammatory Effects on Peripheral Blood Mononuclear Cells from Rheumatoid Arthritis Patients
by Bartolo Tamburini, Diana Di Liberto, Giovanni Pratelli, Chiara Rizzo, Lidia La Barbera, Marianna Lauricella, Daniela Carlisi, Antonella Maggio, Antonio Palumbo Piccionello, Antonella D’Anneo, Nadia Caccamo and Giuliana Guggino
Antioxidants 2025, 14(2), 171; https://doi.org/10.3390/antiox14020171 - 31 Jan 2025
Viewed by 575
Abstract
Rheumatoid arthritis (RA) is a long-term systemic autoimmune disorder that causes joint inflammation, swelling, pain, bone erosion, and deformities. Recent findings emphasize the anti-inflammatory and antioxidant properties of bioactive natural compounds, such as polyphenols extracted from plants and fruits, and their possible synergistic [...] Read more.
Rheumatoid arthritis (RA) is a long-term systemic autoimmune disorder that causes joint inflammation, swelling, pain, bone erosion, and deformities. Recent findings emphasize the anti-inflammatory and antioxidant properties of bioactive natural compounds, such as polyphenols extracted from plants and fruits, and their possible synergistic effect when used in combination with current therapies to improve the prognosis and symptoms of inflammatory rheumatic diseases. Here, we report that Sicilian extra virgin olive oil polyphenol-enriched extracts (PE-EVOOs) reduce intracellular reactive oxygen species (ROS) and pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β), in peripheral mononuclear cells (PBMCs) obtained from both RA patients and healthy subjects (HSs) treated with lipopolysaccharides (LPS) as a control. HPLC-ESI-MS analysis highlighted that PE-EVOOs are rich in different polyphenolic compounds responsible for many of the observed biological effects. At molecular levels, Western blotting analyses revealed that PE-EVOO treatment is associated with the downregulation of the phosphorylated and active form of the inflammatory transcription factor NF-κB and the pro-inflammatory enzyme cyclooxygenase 2 (COX2). In addition, PE-EVOOs upregulated the transcription factor Nrf2 and its target antioxidant enzyme catalase and manganese superoxide dismutase (MnSOD). Collectively, these results suggest a possible use of PE-EVOOs as potential adjuvants for the treatment of RA. Full article
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20 pages, 10108 KiB  
Article
Intense Caloric Restriction from Birth Protects the Heart Against Ischemia/Reperfusion Injury and Reduces Reactive Oxygen Species in Ovariectomized Rats
by Vinícius Lopes Cantuária, Cíntia Maria Rodrigues, Isabella Rocha Dias, Vinícius de Oliveira Ottone, Bruna Oliveira Costa, Lourdes Fernanda Godinho, Gabriela Silva, Marco Antônio Alves Schetino, Etel Rocha-Vieira, Marco Fabrício Dias-Peixoto and Kinulpe Honorato-Sampaio
Antioxidants 2025, 14(2), 169; https://doi.org/10.3390/antiox14020169 - 31 Jan 2025
Viewed by 423
Abstract
This study investigates the cardioprotective effects of intense caloric restriction (ICR) from birth in ovariectomized rats, a model of estrogen deficiency mimicking menopause. Our findings demonstrate that ICR significantly improved both basal and post-ischemic cardiac function, even in the absence of estrogens. The [...] Read more.
This study investigates the cardioprotective effects of intense caloric restriction (ICR) from birth in ovariectomized rats, a model of estrogen deficiency mimicking menopause. Our findings demonstrate that ICR significantly improved both basal and post-ischemic cardiac function, even in the absence of estrogens. The restricted animals exhibited enhanced cardiac contractility and relaxation, particularly after ischemia/reperfusion (I/R) injury, with superior functional recovery compared to control groups. Notably, ICR reduced key cardiometabolic risk factors, including blood pressure, heart rate, and adiposity, while improving glucose tolerance and insulin sensitivity. Additionally, while mitochondrial biogenesis remained unaffected, ICR preserved mitochondrial integrity by reducing the number of damaged mitochondria. This was linked to a reduction in oxidative stress, as evidenced by lower reactive oxygen species (ROS) production in the hearts of restricted animals. These results suggest that ICR offers a protective effect against cardiovascular dysfunction induced by estrogen depletion, potentially through enhanced antioxidant defenses and mitochondrial protection. Full article
(This article belongs to the Special Issue Novel Antioxidant Mechanisms for Health and Diseases)
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25 pages, 1261 KiB  
Article
Energy Intake-Dependent Genetic Associations with Obesity Risk: BDNF Val66Met Polymorphism and Interactions with Dietary Bioactive Compounds
by Ting Zhang and Sunmin Park
Antioxidants 2025, 14(2), 170; https://doi.org/10.3390/antiox14020170 - 30 Jan 2025
Viewed by 431
Abstract
Obesity represents a complex interplay between genetics, nutrition, and lifestyle. This study aimed to elucidate the intricate relationship between genetic variants, energy intake, and bioactive compounds in influencing obesity risk, particularly in low energy intake, to reveal how dietary intake modulates molecular-level interactions. [...] Read more.
Obesity represents a complex interplay between genetics, nutrition, and lifestyle. This study aimed to elucidate the intricate relationship between genetic variants, energy intake, and bioactive compounds in influencing obesity risk, particularly in low energy intake, to reveal how dietary intake modulates molecular-level interactions. We analyzed 53,117 participants stratified by obesity status and energy intake levels. Genome-wide association studies explored the genetic variants associated with obesity risk in low-energy- and high-energy-intake subgroups. Advanced computational approaches, including molecular docking, k-means clustering, and uniform manifold approximation and projection (UMAP), were employed to analyze interactions between missense variants and natural compounds. Ten genetic variants were significantly associated with obesity, particularly in participants with low energy intake. The most prominent variants included brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265). Molecular docking identified 152 bioactive compounds with strong binding affinity to BDNF Val66Met, including 107 compounds binding to both wild and mutant types. Citrus fruits and green vegetables showed selective binding to the mutant type. Antioxidant nutrient intake (anthocyanins, isoflavonoids, vitamins C and E, selenium) was higher in lean versus obese individuals in the high-energy-intake group. Alcohol consumption and selenium intake modulated polygenic risk scores’ influence on obesity risk in high-energy-intake individuals. Notably, citrus fruit intake correlated with lower BMI across all BDNF rs6265 genotypes. In conclusion, energy intake-specific genetic associations with obesity and identifies potential bioactive compounds for targeted interventions. The findings suggest that antioxidant nutrient intake, particularly from citrus fruits, may help manage obesity risk, especially in individuals with specific genetic variants. Full article
25 pages, 2140 KiB  
Article
Curcumin Attenuates Fumonisin B1-Induced PK-15 Cell Apoptosis by Upregulating miR-1249 Expression to Inhibit the IRE1/MKK7/JNK/CASPASE3 Signaling Pathway
by Jia Chen, Dongwei Xiong and Miao Long
Antioxidants 2025, 14(2), 168; https://doi.org/10.3390/antiox14020168 - 30 Jan 2025
Viewed by 338
Abstract
Fumonisin B1 (FB1) is an important toxin which poses global concerns in terms of food safety. Curcumin (Cur), a natural polyphenolic compound, has strong antioxidant and anti-inflammatory effects. Meanwhile, the mechanisms underlying the mitigation of FB1-induced toxicity by Cur are not fully understood, [...] Read more.
Fumonisin B1 (FB1) is an important toxin which poses global concerns in terms of food safety. Curcumin (Cur), a natural polyphenolic compound, has strong antioxidant and anti-inflammatory effects. Meanwhile, the mechanisms underlying the mitigation of FB1-induced toxicity by Cur are not fully understood, limiting its potential application as a novel feed additive to prevent FB1 toxicity. In this study, porcine kidney cells (PK-15) were used as an experimental model, utilizing mRNA and miRNA transcriptome technologies. The results revealed that Cur upregulated miR-1249 and inhibited the target gene Ern1 in the PK-15 cells, thereby suppressing the IRE1/MKK7/JNK/CASPASE3 endoplasmic reticulum (ER) stress pathway and alleviating FB1-induced cell apoptosis. Cell transfection experiments confirmed that Cur effectively attenuated the apoptosis induced by ER stress following transfection with a miR-1249 inhibitor. Similarly, transfection with a miR-1249 mimic alleviated the ER stress and FB1-induced PK-15 cell apoptosis. These findings reveal that Cur mitigates FB1-induced ER stress and significantly reduces apoptotic damage in porcine kidney cells. Full article
13 pages, 1431 KiB  
Article
The Role of Paraoxonase-1 Activity, Apolipoprotein B Levels, and Apolipoprotein B/Apolipoprotein A-I Ratio as Risk Markers for Aortic Stenosis in Patients with a Bicuspid Aortic Valve
by Maria Kwiatkowska, Agnieszka Mickiewicz, Aleksandra Krzesińska, Agnieszka Kuchta, Maciej Jankowski, Marcin Gruchała and Marcin Fijałkowski
Antioxidants 2025, 14(2), 167; https://doi.org/10.3390/antiox14020167 - 30 Jan 2025
Viewed by 416
Abstract
The bicuspid aortic valve (BAV) is commonly associated with the early degeneration of the aortic valve. Up to 45% of BAV patients over the age of 50 develop aortic stenosis (AS). Although published data indicate a robust interplay between lipids and calcific AS [...] Read more.
The bicuspid aortic valve (BAV) is commonly associated with the early degeneration of the aortic valve. Up to 45% of BAV patients over the age of 50 develop aortic stenosis (AS). Although published data indicate a robust interplay between lipids and calcific AS in tricuspid aortic valve patients, the studies on the BAV population are lacking. We aimed to evaluate the association between selected lipid markers and the occurrence of AS in BAV patients. Methods: The study included 76 adults (21 female) with a BAV diagnosed by echocardiography, divided by age and AS diagnosis. Biochemical parameters concentrations in serum were measured: high density lipoprotein cholesterol (HDL-C) levels by standard enzymatic colorimetric tests, low density lipoprotein cholesterol (LDL-C) levels by the Friedewald formula, apolipoprotein A-I (Apo AI) and apolipoprotein B (Apo B) serum concentration by the nephelometric method, and paraoxonase-1 activity (PON-1 ASE) and arylesterase activity (PON-1 ARE) based on paraoxon and phenyl acetate hydrolysis. Results: A total of 54 patients (15 female) were more than 45 years old and 22 (6 female) were 45 or less years old. BAV patients with AS aged ≤45 had higher levels of Apo B, compared to those without AS [110.5 (102–132) vs. 95.6 (77–101) mg/d; p 0.044]. Similarly, Apo B/Apo AI ratio was higher in BAV patients with AS aged ≤45, compared to those without AS [(0.8 (0.7–1) vs. 0.6 (0.5–0.7); p 0.029]. In the group aged ≤45, Apo B showed a positive correlation with the aortic valve peak transvalvular velocity (AV Vmax) measurement (R Spearman 0.6, p 0.004). We found also that, among young BAV patients, those with AS had a lower level of PON-1 ARE compared to the cohort without AS [63.4 (52–80) vs. 85.3 (70–102); p 0.012]. We did not find any differences in lipid parameters in patients aged >45. Conclusions The metabolic link between Apo B level and Apo B/AI ratio with AS presence in BAV patients under 45 years of age suggests a significant impact of these parameters on the earlier development of AS in the BAV population. Molecules associated with high density lipoprotein and its antioxidant function, such as PON1, are valuable markers for AS development, compared to HDL-C and LDL-C levels. Full article
(This article belongs to the Special Issue Antioxidant Role of High-Density Lipoprotein)
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24 pages, 7385 KiB  
Article
Therapeutic Effects of Lavender Oil on Streptozotocin-Induced Diabetes Mellitus and Experimental Thrombosis
by Valeriu Mihai But, Vasile Rus, Tamás Ilyés, Mădălina Luciana Gherman, Ioana Cristina Stănescu, Sorana D. Bolboacă and Adriana Elena Bulboacă
Antioxidants 2025, 14(2), 166; https://doi.org/10.3390/antiox14020166 - 30 Jan 2025
Viewed by 853
Abstract
Diabetes mellitus is a metabolic disorder associated with oxidative stress, inflammation, and coagulation disturbances, which contribute to microvascular and macrovascular complications. We evaluated the therapeutic effects of lavender oil (Lavandula angustifolia) in a streptozotocin (STZ)-induced rat model of type 1 diabetes [...] Read more.
Diabetes mellitus is a metabolic disorder associated with oxidative stress, inflammation, and coagulation disturbances, which contribute to microvascular and macrovascular complications. We evaluated the therapeutic effects of lavender oil (Lavandula angustifolia) in a streptozotocin (STZ)-induced rat model of type 1 diabetes mellitus (T1DM) with experimentally induced thrombosis. Sixty male Wistar rats were divided into control, thrombosis, diabetes, thrombosis–diabetes, and lavender oil pretreatment groups (100 and 200 mg/kg body weight [bw]). Lavender oil exhibited dose-dependent benefits, with the 200 mg/kg bw dose leading to significant reductions in proinflammatory cytokines (e.g., tumor necrosis factor α (TNF-α); regulated upon activation, normal T cell expressed and secreted (RANTES); and monocyte chemoattractant protein-1 (MCP-1)) and oxidative stress, along with improved glycemic control, the partial restoration of C-peptide levels, and the attenuation of matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9) activity (p < 0.0001). Histopathological and coagulation analyses confirmed its organ-protective and antithrombotic effects, including reduced tissue damage, vascular inflammation, and thrombus formation, and prolonged bleeding and clotting times. Our findings suggest that lavender oil exhibits dose-dependent antioxidant, anti-inflammatory, hypoglycemic, and organ-protective effects, indicating its potential as a complementary therapy for managing inflammation in T1DM with or without thrombosis. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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17 pages, 553 KiB  
Review
Association Between Zinc Levels and the Impact of Its Deficiency on Idiopathic Male Infertility: An Up-to-Date Review
by Nebojša Zečević, Aleksandra Veselinović, Milan Perović and Aleksandar Stojsavljević
Antioxidants 2025, 14(2), 165; https://doi.org/10.3390/antiox14020165 - 29 Jan 2025
Viewed by 283
Abstract
Background: Zinc (Zn) is an essential metal that plays a critical role in normal testicular development, spermatogenesis, prevention of sperm degradation, and overall male fertility. This review aims to offer a comprehensive and current overview of seminal plasma Zn levels in fertile men [...] Read more.
Background: Zinc (Zn) is an essential metal that plays a critical role in normal testicular development, spermatogenesis, prevention of sperm degradation, and overall male fertility. This review aims to offer a comprehensive and current overview of seminal plasma Zn levels in fertile men worldwide. It also aims to compare Zn levels in seminal plasma and blood (serum/plasma) between infertile men (cases) and fertile men (controls), examine the impact of Zn on sperm quality and the reproductive hormone, and highlight the effects of Zn supplementation therapy in male infertility. Methods: To achieve these goals, peer-reviewed studies from 2000 to 2024 were interrogated with regard to strict inclusion/exclusion criteria and were then thoroughly reviewed and analyzed. Results: Our findings indicate that maintaining optimal seminal plasma Zn levels is crucial, as low Zn levels are linked to impaired spermatogenesis and male infertility, while high Zn levels can cause oxidative stress and other changes that contribute to infertility. Seminal plasma Zn levels from 100 to 200 mg/L among fertile men worldwide can be roughly considered safe. Comparative analysis showed that a greater number of studies reported lower levels of seminal Zn in cases than in controls. Research into the impact of Zn levels in seminal plasma has shown that, although the results are not yet conclusive, altered (non-normal) Zn levels could influence semen parameters—particularly motility, morphology, and sperm count—and the level of the reproductive hormone, testosterone. Zinc-deficient infertile men could benefit from supplement therapy. Conclusions: Assessment of seminal plasma Zn levels in infertile men could provide valuable information and aid in diagnosis and treatment planning. Full article
(This article belongs to the Section Antioxidant Enzyme Systems)
29 pages, 610 KiB  
Article
Antioxidant, Antithrombotic and Anti-Inflammatory Properties of Amphiphilic Bioactives from Water Kefir Grains and Its Apple Pomace-Based Fermented Beverage
by Dimitra Papadopoulou, Vasiliki Chrysikopoulou, Aikaterini Rampaouni, Christos Plakidis, Anna Ofrydopoulou, Katie Shiels, Sushanta Kumar Saha and Alexandros Tsoupras
Antioxidants 2025, 14(2), 164; https://doi.org/10.3390/antiox14020164 - 29 Jan 2025
Viewed by 475
Abstract
Kefir-based fermentation products exhibit antioxidant and anti-inflammatory effects against oxidative stress, inflammation, platelet activation and aggregation, and other related manifestations, thereby preventing the onset and development of several chronic diseases. Specifically, water kefir, a symbiotic culture of various microorganisms used for the production [...] Read more.
Kefir-based fermentation products exhibit antioxidant and anti-inflammatory effects against oxidative stress, inflammation, platelet activation and aggregation, and other related manifestations, thereby preventing the onset and development of several chronic diseases. Specifically, water kefir, a symbiotic culture of various microorganisms used for the production of several bio-functional fermented products, has been proposed for its health-promoting properties. Thus, water kefir grains and its apple pomace-based fermentation beverage were studied for bioactive amphiphilic and lipophilic lipid compounds with antioxidant, antithrombotic, and anti-inflammatory properties. Total lipids(TL) were extracted and further separated into their total amphiphilic (TAC) and total lipophilic content (TLC), in which the total phenolic and carotenoid contents (TPC and TCC, respectively) and the fatty acid content of the polar lipids (PL) were quantified, while the antioxidant activity of both TAC and TLC were assessed in vitro, by the ABTS, DPPH, and FRAP bioassays, along with the anti-inflammatory and antithrombotic activity of TAC against human platelet aggregation induced by the thrombo-inflammatory mediator, platelet-activating factor (PAF) or standard platelet agonists like ADP.ATR-FTIR spectra facilitated the detection of specific structural, functional groups of phenolic, flavonoid, and carotenoid antioxidants, while LC−MS analysis revealed the presence of specific anti-inflammatory and antithrombotic PL bioactives bearing unsaturated fatty acids in their structures, with favorable omega-6 (n−6)/omega-3 (n−3)polyunsaturated fatty acids (PUFA), which further support the findings that the most potent antioxidant, anti-inflammatory and antithrombotic bioactivities were observed in the TAC extracts, in both water kefir grains and beverage cases. The detection of such bioactive components in both the uncultured water kefir grains and in the cultured beverage further supports the contribution of water kefir microorganisms to the bioactivity and the bio-functionality of the final fermented product. Nevertheless, the extracts of the beverage showed much stronger antioxidant, anti-inflammatory, and antithrombotic activities, which further suggests that during the culture process for producing this beverage, not only was the presence of bioactive compounds produced by kefir microflora present, but biochemical alterations during fermentation of bioactive components derived from apple pomace also seemed to have taken place, contributing to the higher bio-functionality observed in the apple pomace—water kefir-based beverage, even when compared to the unfermented apple pomace. The overall findings support further studies on the use of water kefir and/or apple pomace as viable sources of antioxidant, anti-inflammatory, and antithrombotic amphiphilic bioactive compounds for the production of novel health-promoting bio-functional fermented products. Full article
(This article belongs to the Special Issue Antioxidants from Sustainable Food Sources)
18 pages, 2376 KiB  
Article
Myocardial DYRK1B Expression Is Increased in Patients with Impaired Cardiac Contractility and Sleep-Disordered Breathing
by Fatma Bayram, Philipp Hegner, Anna-Maria Lauerer, Sönke Schildt, Dominik Wermers, Maria Johanna Baier, Julian Mustroph, Maria Tafelmeier, Zdenek Provaznik, Christof Schmid, Lars Siegfried Maier, Stefan Wagner, Michael Arzt and Simon Lebek
Antioxidants 2025, 14(2), 163; https://doi.org/10.3390/antiox14020163 - 29 Jan 2025
Viewed by 631
Abstract
Heart failure and cardiovascular disease represent a significant burden on healthcare systems worldwide. Recent evidence associates an increased expression of the dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B) with an impaired cardiac function in mice. However, there remains a paucity of data on myocardial [...] Read more.
Heart failure and cardiovascular disease represent a significant burden on healthcare systems worldwide. Recent evidence associates an increased expression of the dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B) with an impaired cardiac function in mice. However, there remains a paucity of data on myocardial DYRK1B expression in patients with cardiovascular disease in the context of other comorbidities. In our study, we examined DYRK1B mRNA expression in human right atrial appendage biopsies from 159 patients undergoing elective coronary artery bypass surgery. Each patient was tested for sleep-disordered breathing the night prior to surgery. In this large representative study cohort with cardiovascular high-risk patients, we found that an impaired cardiac function as well as sleep-disordered breathing (SDB), including various oxidative stress parameters, were associated with an increased myocardial DYRK1B expression. A multivariate regression analysis revealed left ventricular ejection fraction and the presence of SDB as significant predictors of the myocardial DYRK1B expression independent of other clinical covariates. Based on these findings, DYRK1B represents a promising molecular target in patients with heart failure and reduced ejection fraction as well in patients with sleep-disordered breathing. Full article
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19 pages, 7584 KiB  
Article
Causal Impacts of Psychiatric Disorders on Cognition and the Mediating Effect of Oxidative Stress: A Mendelian Randomization Study
by Yan Gao, Dandan Wang, Qian Wang, Jinfeng Wang, Shuhui Li, Tianqi Wang, Xiaowen Hu and Chunling Wan
Antioxidants 2025, 14(2), 162; https://doi.org/10.3390/antiox14020162 - 29 Jan 2025
Viewed by 422
Abstract
Many psychiatric disorders are associated with major cognitive deficits. However, it is uncertain whether these deficits develop as a result of psychiatric disorders and what shared risk factors might mediate this relationship. Here, we utilized the Mendelian randomization (MR) analysis to investigate the [...] Read more.
Many psychiatric disorders are associated with major cognitive deficits. However, it is uncertain whether these deficits develop as a result of psychiatric disorders and what shared risk factors might mediate this relationship. Here, we utilized the Mendelian randomization (MR) analysis to investigate the complex causal relationship between nine major psychiatric disorders and three cognitive phenotypes, while also examining the potential mediating role of oxidative stress as a shared biological underpinning. Schizophrenia (SZ), major depressive disorder (MDD), and attention deficit hyperactivity disorder (ADHD) showed a decreasing effect on cognitive performance, intelligence, and education, while bipolar disorder (BPD) increased educational attainment. MR-Clust results exhibit the shared genetic basis between SZ and other psychiatric disorders in relation to cognitive function. Furthermore, when oxidative stress was considered as a potential mediating factor, the associations between SZ and the three dimensions of cognition, as well as between MDD and intelligence and ADHD and intelligence, exhibited larger effect sizes than the overall. Mediation MR analysis also supported the causal effects between psychiatric disorders and cognition via oxidative stress traits, including carotene, vitamin E, bilirubin, and uric acid. Finally, summary-based MR identified 29 potential causal associations of oxidative stress genes with both cognitive performance and psychiatric disorders. Our findings highlight the importance of considering oxidative stress in understanding and potentially treating cognitive impairments associated with psychiatric conditions. Full article
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19 pages, 3898 KiB  
Article
High Rosmarinic Acid Content Melissa officinalis L. Phytocomplex Modulates Microglia Neuroinflammation Induced by High Glucose
by Giacomina Videtta, Chiara Sasia and Nicoletta Galeotti
Antioxidants 2025, 14(2), 161; https://doi.org/10.3390/antiox14020161 - 29 Jan 2025
Viewed by 465
Abstract
Diabetic patients experience hyperglycemia, which can affect multiple organs, including brain function, leading to disabling neurological complications. Hyperglycemia plays a key role in promoting neuroinflammation, the most common complication in diabetic individuals, through the activation of microglia. Attenuating hyperglycemia-related neuroinflammation in microglia may [...] Read more.
Diabetic patients experience hyperglycemia, which can affect multiple organs, including brain function, leading to disabling neurological complications. Hyperglycemia plays a key role in promoting neuroinflammation, the most common complication in diabetic individuals, through the activation of microglia. Attenuating hyperglycemia-related neuroinflammation in microglia may reduce diabetes-associated neurological comorbidities. Natural remedies containing phenolic compounds have shown efficacy in mitigating microglia-mediated neuroinflammation. The aim of this study was to investigate the potential of a Melissa officinalis L. (MO) phytocomplex, obtained from plant cell cultures and enriched in its main polyphenolic constituent, rosmarinic acid (RA), in attenuating hyperglycemia-induced neuroinflammation in microglia. A time-course morphological analysis of BV2 microglial cells exposed to high glucose (HG) levels showed a shift towards a proinflammatory phenotype, peaking after 48 h, which was reversed by pretreatment with MO. Biochemical assays revealed increased expression of the microglial marker CD11b (187%), activation of the NF-κB pathway (179%), expression of iNOS (225%), enhanced phosphorylation of ERK1/2 (180%), and increased expression of the proinflammatory cytokine IL-6 (173%). Pretreatment with MO prevented the aberrant expression of these proinflammatory mediators and restored SIRT1 levels. Exposure of neuronal SH-SY5Y cells to the conditioned medium from HG-exposed microglia significantly reduced cell viability. MO counteracted this effect, exhibiting neuroprotective activity. RA showed efficacy comparable to that of MO. In conclusion, MO and RA attenuated microglia-mediated oxidative imbalance and neuroinflammation under HG exposure by inhibiting the morphological shift toward a proinflammatory phenotype induced by HG and abrogating the subsequent activation of the downstream ERK1/2–NF-κB–iNOS pathway. Full article
(This article belongs to the Special Issue Plant Antioxidants, Inflammation, and Chronic Disease)
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19 pages, 5996 KiB  
Article
Effect of Photoperiod on Ascorbic Acid Metabolism Regulation and Accumulation in Rapeseed (Brassica napus L.) Seedlings
by Chao Wang, Lieqiong Kuang, Ze Tian, Xinfa Wang, Jinxing Tu, Hanzhong Wang and Xiaoling Dun
Antioxidants 2025, 14(2), 160; https://doi.org/10.3390/antiox14020160 - 29 Jan 2025
Viewed by 459
Abstract
Ascorbic acid (AsA) is an important antioxidant for human health. The concept of “oil-vegetable-duel-purpose” can significantly enhance the economic benefits of the rapeseed industry. Rapeseed, when utilized as a vegetable, serves as a valuable food source of AsA. In this study, we integrated [...] Read more.
Ascorbic acid (AsA) is an important antioxidant for human health. The concept of “oil-vegetable-duel-purpose” can significantly enhance the economic benefits of the rapeseed industry. Rapeseed, when utilized as a vegetable, serves as a valuable food source of AsA. In this study, we integrated transcriptome and metabolome analyses, along with substrate feeding, to identify the L-galactose pathway as the primary source for AsA production, which is primarily regulated by light. Through seven different photoperiod treatments from 12 h/12 h (light/dark) to 24 h/0 h, we found that AsA content increased with longer photoperiods, as well as chlorophyll, carotenoids, and soluble sugars. However, an excessively long photoperiod led to photooxidative stress, which negatively affected biomass accumulation in rapeseed seedlings and subsequently impacted the total accumulation of AsA. Furthermore, different enzymes respond differently to different photoperiods. Analysis of the correlation between the expression levels of AsA biosynthesis-related genes and AsA content highlighted a dynamic balancing mechanism of AsA metabolism in response to different photoperiods. The study revealed that the 16 h/8 h photoperiod is optimal for long-term AsA accumulation in rapeseed seedlings. However, extending the photoperiod before harvest can enhance AsA content without compromising yield. These findings offer novel insights into an effective strategy for the biofortification of AsA in rapeseed. Full article
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