Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Article Types

Countries / Regions

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Search Results (397)

Search Parameters:
Keywords = cholesterol oxidative products

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
19 pages, 1021 KiB  
Article
Causal Inference Approaches Reveal Associations Between LDL Oxidation, NO Metabolism, Telomere Length and DNA Integrity Within the MARK-AGE Study
by Andrei Valeanu, Denisa Margina, María Moreno-Villanueva, María Blasco, Ewa Sikora, Grazyna Mosieniak, Miriam Capri, Nicolle Breusing, Jürgen Bernhardt, Christiane Schön, Olivier Toussaint, Florence Debacq-Chainiaux, Beatrix Grubeck-Loebenstein, Birgit Weinberger, Simone Fiegl, Efstathios S. Gonos, Antti Hervonen, Eline P. Slagboom, Anton de Craen, Martijn E. T. Dollé, Eugène H. J. M. Jansen, Eugenio Mocchegiani, Robertina Giacconi, Francesco Piacenza, Marco Malavolta, Daniela Weber, Wolfgang Stuetz, Tilman Grune, Claudio Franceschi, Alexander Bürkle and Daniela Gradinaruadd Show full author list remove Hide full author list
Antioxidants 2025, 14(8), 933; https://doi.org/10.3390/antiox14080933 - 30 Jul 2025
Viewed by 281
Abstract
Genomic instability markers are important hallmarks of aging, as previously evidenced within the European study of biomarkers of human aging, MARK-AGE; however, establishing the specific metabolic determinants of vascular aging is challenging. The objective of the present study was to evaluate the impact [...] Read more.
Genomic instability markers are important hallmarks of aging, as previously evidenced within the European study of biomarkers of human aging, MARK-AGE; however, establishing the specific metabolic determinants of vascular aging is challenging. The objective of the present study was to evaluate the impact of the susceptibility to oxidation of serum LDL particles (LDLox) and the plasma metabolization products of nitric oxide (NOx) on relevant genomic instability markers. The analysis was performed on a MARK-AGE cohort of 1326 subjects (635 men and 691 women, 35–75 years old) randomly recruited from the general population. The Inverse Probability of Treatment Weighting causal inference algorithm was implemented in order to assess the potential causal relationship between the LDLox and NOx octile-based thresholds and three genomic instability markers measured in mononuclear leukocytes: the percentage of telomeres shorter than 3 kb, the initial DNA integrity, and the DNA damage after irradiation with 3.8 Gy. The results showed statistically significant telomere shortening for LDLox, while NOx yielded a significant impact on DNA integrity. Overall, the effect on the genomic instability markers was higher than for the confirmed vascular aging determinants, such as low HDL cholesterol levels, indicating a meaningful impact even for small changes in LDLox and NOx values. Full article
(This article belongs to the Special Issue Exploring Biomarkers of Oxidative Stress in Health and Disease)
Show Figures

Figure 1

17 pages, 1463 KiB  
Article
Linseed, Walnut, and Algal Oil Emulsion Gels as Fat Replacers in Chicken Frankfurters: Effects on Composition, Lipid Profile and Sensory Quality
by Tamara Stamenić, Vanja Todorović, Maja Petričević, Tanja Keškić, Bogdan Cekić, Nenad Stojiljković and Nikola Stanišić
Foods 2025, 14(15), 2677; https://doi.org/10.3390/foods14152677 - 30 Jul 2025
Viewed by 411
Abstract
The replacement of animal fat with unsaturated lipid sources in processed meats enhances nutritional value but introduces challenges regarding oxidative stability and sensory acceptability. In this study, the effects of replacing pork back fat with pre-emulsified walnut, linseed, or algal oils on the [...] Read more.
The replacement of animal fat with unsaturated lipid sources in processed meats enhances nutritional value but introduces challenges regarding oxidative stability and sensory acceptability. In this study, the effects of replacing pork back fat with pre-emulsified walnut, linseed, or algal oils on the proximate composition, fatty acid profile, nutritional indices, lipid oxidation, and sensory properties of chicken frankfurters were investigated. Four formulations were prepared: a control group (25% pork fat) and three groups that were completely reformulated using oil emulsions (ratio inulin/water/oil 1:2:1). The fat substitute significantly reduced total fat, SFA, cholesterol (up to 30%), and calorie density, while Ʃn-3 fatty acids were enriched (p < 0.05). The linseed oil samples had the highest levels of α-linolenic acid (47.53%), while the algal oil had the highest levels of eicosapentaenoic acid (10.98%) and docosahexaenoic acid (64.73%) and the most favourable Ʃn-6/Ʃn-3 ratio (p < 0.05). All reformulated groups showed significantly improved atherogenic and thrombogenic indices and increased hypocholesterolaemic/hypercholesterolaemic ratios, which reached 17.43 in the algal oil samples (p < 0.05). Lipid oxidation was increased in the linseed and algal oil treatments, with the walnut oil group showing moderate TBARS levels and minimal accumulation of secondary oxidation products. Principal component analysis revealed that walnut oil offered the most balanced compromise between nutritional improvement, oxidative stability and sensory acceptability. These findings support a healthier reformulation of meat products by identifying oil-based fat substitutes that improve nutritional value without compromising sensory quality, which is beneficial for both research and industry. Full article
(This article belongs to the Section Food Physics and (Bio)Chemistry)
Show Figures

Figure 1

29 pages, 4588 KiB  
Article
The HCV-Dependent Inhibition of Nrf1/ARE-Mediated Gene Expression Favours Viral Morphogenesis
by Olga Szostek, Patrycja Schorsch, Daniela Bender, Mirco Glitscher and Eberhard Hildt
Viruses 2025, 17(8), 1052; https://doi.org/10.3390/v17081052 - 28 Jul 2025
Viewed by 325
Abstract
The life cycle of the hepatitis C virus (HCV) is closely linked to lipid metabolism. Recently, the stress defence transcription factor, nuclear factor erythroid 2 related factor-1 (Nrf1), has been described as a cholesterol sensor that protects the liver from excess cholesterol. Nrf1, [...] Read more.
The life cycle of the hepatitis C virus (HCV) is closely linked to lipid metabolism. Recently, the stress defence transcription factor, nuclear factor erythroid 2 related factor-1 (Nrf1), has been described as a cholesterol sensor that protects the liver from excess cholesterol. Nrf1, like its homologue Nrf2, further responds to oxidative stress by binding with small Maf proteins (sMaf) to the promotor antioxidant response element (ARE). Given these facts, investigating the crosstalk between Nrf1 and HCV was a logical next step. In HCV-replicating cells, we observed reduced levels of Nrf1. Furthermore, activation of Nrf1-dependent target genes is impaired due to sMaf sequestration in replicase complexes. This results in a shortage of sMaf proteins in the nucleus, trapping Nrf1 at the replicase complexes and further limiting its function. Weakened Nrf1 activity contributes to impaired cholesterol removal, which occurs alongside an elevated intracellular cholesterol level and inhibited LXRα promoter activation. Furthermore, inhibition of Nrf1 activity correlated with a kinome profile characteristic of steatosis and enhanced inflammation—factors contributing to HCV pathogenesis. Our results indicate that activation of Nrf1-dependent target genes is impaired in HCV-positive cells. This, in turn, favours viral morphogenesis, as evidenced by enhanced replication and increased production of viral progeny. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
Show Figures

Figure 1

19 pages, 3827 KiB  
Article
A Refined Carbohydrate-Rich Diet Reduces Vascular Reactivity Through Endothelial Oxidative Stress and Increased Nitric Oxide: The Involvement of Inducible Nitric Oxide Synthase
by Karoline Neumann, Nina Bruna de Souza Mawandji, Ingridy Reinholz Grafites Schereider, Emanuelle Coutinho de Oliveira, Julia Martins Vieira, Andressa Bolsoni-Lopes, Jones Bernardes Graceli, Julia Antonietta Dantas, Lorena Silveira Cardoso, Dalton Valentim Vassallo and Karolini Zuqui Nunes
Nutrients 2025, 17(15), 2395; https://doi.org/10.3390/nu17152395 - 22 Jul 2025
Viewed by 316
Abstract
Background/Objectives: The consumption of refined carbohydrates has increased globally. It is associated with inflammation and oxidative stress, both recognized as risk factors for cardiovascular disease. This study investigated the effects of a refined carbohydrate-rich diet on the vascular reactivity of rat aorta. Methods: [...] Read more.
Background/Objectives: The consumption of refined carbohydrates has increased globally. It is associated with inflammation and oxidative stress, both recognized as risk factors for cardiovascular disease. This study investigated the effects of a refined carbohydrate-rich diet on the vascular reactivity of rat aorta. Methods: We acclimatized adult male Wistar rats for two weeks and then randomly assigned them to two experimental groups: a control (CT) group and a high-carbohydrate diet (HCD) group. The CT group received standard laboratory chow for 15 days, while the HCD group received a diet composed of 45% sweetened condensed milk, 10% refined sugar, and 45% standard chow. After the dietary exposure period, we evaluated the vascular reactivity of aortic rings, gene expression related to inflammation, superoxide dismutase activity, and biochemical parameters, including cholesterol, triglycerides, fasting glucose, and glucose and insulin tolerance. Results: The results demonstrate a reduction in vascular reactivity caused by endothelial alterations, including increased NO production, which was observed as higher vasoconstriction in the presence of L-NAME and aminoguanidine and upregulation of iNOS gene expression. In addition, increased production of free radicals, such as O2-, was observed, as well as immune markers like MCP-1 and CD86 in the HCD group. Additionally, the HCD group showed an increase in the TyG index, suggesting early metabolic impairment. GTT and ITT results revealed higher glycemic levels, indicating early signs of insulin resistance. Conclusions: These findings indicate that short-term consumption of a refined carbohydrate-rich diet may trigger oxidative stress and endothelial dysfunction, thereby increasing the risk of cardiovascular complications. Full article
(This article belongs to the Section Nutrition and Metabolism)
Show Figures

Graphical abstract

22 pages, 2139 KiB  
Article
Nutritional and Technological Benefits of Pine Nut Oil Emulsion Gel in Processed Meat Products
by Berik Idyryshev, Almagul Nurgazezova, Zhanna Assirzhanova, Assiya Utegenova, Shyngys Amirkhanov, Madina Jumazhanova, Assemgul Baikadamova, Assel Dautova, Assem Spanova and Assel Serikova
Foods 2025, 14(15), 2553; https://doi.org/10.3390/foods14152553 - 22 Jul 2025
Viewed by 334
Abstract
A high intake of saturated fats and cholesterol from processed meats is associated with increased cardiovascular disease risk. This study aimed to develop a nutritionally enhanced Bologna-type sausage by partially replacing the beef content with a structured emulsion gel (EG) formulated from pine [...] Read more.
A high intake of saturated fats and cholesterol from processed meats is associated with increased cardiovascular disease risk. This study aimed to develop a nutritionally enhanced Bologna-type sausage by partially replacing the beef content with a structured emulsion gel (EG) formulated from pine nut oil, inulin, carrageenan, and whey protein concentrate. The objective was to improve its lipid quality and functional performance while maintaining product integrity and consumer acceptability. Three sausage formulations were prepared: a control and two variants with 7% and 10% EG, which substituted for the beef content. The emulsion gel was characterized regarding its physical and thermal stability. Sausages were evaluated for their proximate composition, fatty acid profile, cholesterol content, pH, cooking yield, water-holding capacity, emulsion stability, instrumental texture, microstructure (via SEM), oxidative stability (TBARSs), and sensory attributes. Data were analyzed using a one-way and two-way ANOVA with Duncan’s test (p < 0.05). The EG’s inclusion significantly reduced the total and saturated fat and cholesterol, while increasing protein and unsaturated fatty acids. The 10% EG sample achieved a PUFA/SFA ratio of 1.00 and an over 80% reduction in atherogenic and thrombogenic indices. Functional improvements were observed in emulsion stability, cooking yield, and water retention. Textural and visual characteristics remained within acceptable sensory thresholds. SEM images showed more homogenous matrix structures in the EG samples. TBARS values increased slightly over 18 days of refrigeration but remained below rancidity thresholds. This period was considered a pilot-scale evaluation of oxidative trends. Sensory testing confirmed that product acceptability was not negatively affected. The partial substitution of beef content with pine nut oil-based emulsion gel offers a clean-label strategy to enhance the nutritional quality of Bologna-type sausages while preserving functional and sensory performance. This approach may support the development of health-conscious processed meat products aligned with consumer and regulatory demands. Full article
(This article belongs to the Section Meat)
Show Figures

Figure 1

53 pages, 2310 KiB  
Review
Metabolic Reprogramming in Respiratory Viral Infections: A Focus on SARS-CoV-2, Influenza, and Respiratory Syncytial Virus
by Jordi Camps, Simona Iftimie, Andrea Jiménez-Franco, Antoni Castro and Jorge Joven
Biomolecules 2025, 15(7), 1027; https://doi.org/10.3390/biom15071027 - 16 Jul 2025
Viewed by 512
Abstract
Respiratory infections caused by severe acute respiratory syndrome coronavirus 2, influenza virus, and respiratory syncytial virus pose significant global health challenges, leading to high morbidity and mortality, particularly in vulnerable populations. Despite their distinct virological characteristics, these viruses exploit host cellular metabolism to [...] Read more.
Respiratory infections caused by severe acute respiratory syndrome coronavirus 2, influenza virus, and respiratory syncytial virus pose significant global health challenges, leading to high morbidity and mortality, particularly in vulnerable populations. Despite their distinct virological characteristics, these viruses exploit host cellular metabolism to support replication, modulate immune responses, and promote disease progression. Emerging evidence shows that they induce metabolic reprogramming, shifting cellular energy production toward glycolysis to meet the bioenergetic demands of viral replication. Additionally, alterations in lipid metabolism, including enhanced fatty acid synthesis and disrupted cholesterol homeostasis, facilitate viral entry, replication, and immune evasion. The dysregulation of mitochondrial function and oxidative stress pathways also contributes to disease severity and long-term complications, such as persistent inflammation and immune exhaustion. Understanding these metabolic shifts is crucial for identifying new therapeutic targets and novel biomarkers for early disease detection, prognosis, and patient stratification. This review provides an overview of the metabolic alterations induced by severe acute respiratory syndrome coronavirus 2, influenza virus, and respiratory syncytial virus, highlighting shared and virus-specific mechanisms and potential therapeutic interventions. Full article
Show Figures

Figure 1

16 pages, 614 KiB  
Article
Bioactive Properties of Persea americana Peel Extract and Their Role in Hypercholesterolemia Management and Cardiovascular Health
by Laura M. Teixeira, Catarina P. Reis and Rita Pacheco
Foods 2025, 14(14), 2482; https://doi.org/10.3390/foods14142482 - 16 Jul 2025
Viewed by 237
Abstract
Cardiovascular diseases remain the leading cause of death worldwide, with hypercholesterolemia being a major contributing risk factor. Although cholesterol-lowering drugs are widely available, concerns about several adverse side effects have increased the demand for natural alternatives, with the most common approaches involving the [...] Read more.
Cardiovascular diseases remain the leading cause of death worldwide, with hypercholesterolemia being a major contributing risk factor. Although cholesterol-lowering drugs are widely available, concerns about several adverse side effects have increased the demand for natural alternatives, with the most common approaches involving the incorporation of foods rich in bioactive compounds into the diet. To explore this growing interest in food-based strategies for cardiovascular health, this study formulated and evaluated an aqueous peel extract of Persea americana to assess its potential role as a complementary approach to managing hypercholesterolemia. The extract was characterized, revealing the presence of various bioactive compounds, including pyridoxine-O-Hex, which was identified for the first time in a P. americana extract component. The safety profile of the extract was confirmed through in vivo assessment. Furthermore, the extract demonstrated protective effects against oxidative stress in HepG2 cells. Additionally, permeability studies using Caco-2 cells, as a model of the gastrointestinal barrier, indicated that the extract effectively reduced cholesterol’s permeation. In summary, these findings suggest that P. americana peel extract may serve as a promising natural product for functional foods for cardiovascular health and hypercholesterolemia management. Full article
(This article belongs to the Special Issue Advances in Biological Activities of Functional Food (3rd Edition))
Show Figures

Graphical abstract

21 pages, 3852 KiB  
Article
PCSK9 Inhibitor Inclisiran Attenuates Cardiotoxicity Induced by Sequential Anthracycline and Trastuzumab Exposure via NLRP3 and MyD88 Pathway Inhibition
by Vincenzo Quagliariello, Massimiliano Berretta, Irma Bisceglia, Martina Iovine, Matteo Barbato, Raffaele Arianna, Maria Laura Canale, Andrea Paccone, Alessandro Inno, Marino Scherillo, Stefano Oliva, Christian Cadeddu Dessalvi, Alfredo Mauriello, Carlo Maurea, Celeste Fonderico, Anna Chiara Maratea, Domenico Gabrielli and Nicola Maurea
Int. J. Mol. Sci. 2025, 26(14), 6617; https://doi.org/10.3390/ijms26146617 - 10 Jul 2025
Viewed by 435
Abstract
Cardiotoxicity related to anthracyclines and trastuzumab represents a significant clinical challenge in cancer therapy, often limiting treatment efficacy and patient survival. The underlying mechanisms of cardiotoxicity involve the activation of NLRP3 and the MyD88-dependent signaling pathway. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), [...] Read more.
Cardiotoxicity related to anthracyclines and trastuzumab represents a significant clinical challenge in cancer therapy, often limiting treatment efficacy and patient survival. The underlying mechanisms of cardiotoxicity involve the activation of NLRP3 and the MyD88-dependent signaling pathway. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), such as inclisiran, are known for their lipid-lowering effects, but emerging data indicate that they may also exert pleiotropic benefits beyond cholesterol reduction. This study investigates whether inclisiran can mitigate the cardiotoxic effects of anthracyclines and trastuzumab through reduction of NLRP3 activation and MyD88 signaling, independently of its effects on dyslipidemia. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were exposed to subclinical concentrations of doxorubicin (1 µM) and trastuzumab in sequential therapy (200 nM), alone or in combination with inclisiran (100 nM) for 24 h. After the incubation period, we performed the following tests: determination of cardiomyocytes apoptosis, analysis of intracellular reactive oxygen species, lipid peroxidation products (including malondialdehyde and 4-hydroxynonenal), intracellular mitofusin-2 and Ca++ levels. Troponin and BNP were quantified through selective ELISA methods. A confocal laser scanning microscope was used to study cardiomyocyte morphology and F-actin staining after treatments. Moreover, pro-inflammatory studies were also performed, including the intracellular expression of NLRP-3, MyD-88 and twelve cytokines/growth factors involved in cardiotoxicity (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IFN-γ, TNF-α, G-CSF, GM-CSF). Inclisiran co-incubated with doxorubicin and trastuzumab exerts significant cardioprotective effects, enhancing cell viability by 88.9% compared to only DOXO/TRA treated cells (p < 0.001 for all). Significant reduction of oxidative stress, and intracellular levels of NLRP-3, MyD88, IL-1α, IL-1β, IL-6, IL-12, IL17-α, TNF-α, G-CSF were seen in the inclisiran group vs. only DOXO/TRA (p < 0.001). For the first time, PCSK9i inclisiran has been shown to exert significant anti-inflammatory effects to reduce anthracycline-HER-2 blocking agent-mediated cardiotoxicity through NLRP-3 and Myd-88 related pathways. The overall conclusions of the study warrant further investigation of the use of PCSK9i in primary prevention of CTRCD in cancer patients, independently from dyslipidemia. Full article
Show Figures

Figure 1

16 pages, 3566 KiB  
Article
Effects of Dietary β-Carotene on the Gonadal Color, Pigmentation, and Regulation Mechanisms in Sea Urchin Strongylocentrotus Intermedius
by Weixiao Di, Yinuo Zhang, Huinan Zuo, Haijing Liu, Lina Wang, Jun Ding, Yaqing Chang and Rantao Zuo
Fishes 2025, 10(7), 304; https://doi.org/10.3390/fishes10070304 - 24 Jun 2025
Viewed by 370
Abstract
This study aims to clarify the dose–response relationship between dietary β-carotene levels and gonadal pigment deposition and regulation mechanisms related to the carotenoid synthesis of Strongylocentrotus intermedius based on a 60-day feeding trial and subsequent transcriptome analysis. Adult sea urchins (initial weight: 9.33 [...] Read more.
This study aims to clarify the dose–response relationship between dietary β-carotene levels and gonadal pigment deposition and regulation mechanisms related to the carotenoid synthesis of Strongylocentrotus intermedius based on a 60-day feeding trial and subsequent transcriptome analysis. Adult sea urchins (initial weight: 9.33 ± 0.21 g) of three cages were given one of the dry feeds with different doses of β-carotene (0 mg/kg, 150 mg/kg, 300 mg/kg) or fresh kelp (Saccharina japonica). The results indicated that the weight gain rate (WGR) of sea urchins increased with the addition of β-carotene, with that of the C300 group being markedly higher than that of the C0 group. The addition of β-carotene significantly improved the redness (a*) and yellowness (b*) values of the gonads, with sea urchins in the C300 group exhibiting closest gonad coloration to those in the kelp-fed group. Meanwhile, β-carotene and echinenone in the gonads of the C300 group showed the highest contents, reaching 1.96 μg/kg and 11.97 μg/kg, respectively. Several differential genes, enriched in the pathways of steroid biosynthesis, oxidative phosphorylation, and ubiquitination, were screened based on transcriptome analysis. Real-time PCR further demonstrated that β-carotene significantly upregulated the expression of cholesterol 25-hydroxylase (CH25H), NADH dehydrogenase subunit 1 (ND1), NADH dehydrogenase subunit 2 (ND2), and NADH dehydrogenase subunit 4 (ND4) while it downregulated the expression of 24-dehydrocholesterol reductase (DHCR24). These results showed that 300 mg/kg β-carotene significantly increased the WGR, redness, and yellowness values, as well as the contents of β-carotene and echinenone in the gonads of S. intermedius. On the one hand, dietary β-carotene increased NADH enzyme activity, which participates in echinenone synthesis by donating electrons for the transformation of β-carotene to echinenone synthesis. On the other hand, the addition of β-carotene inhibited cholesterol synthesis by increasing the expression of CH25H and decreasing the expression of DHCR24, which could in turn increase the fluidity and permeability of the cell membranes and the transport efficiency of β-carotene and echinenone from the digestive tract to the gonads. These results provided fundamental insights into the production of sea urchin gonads with market-favored colors. Full article
(This article belongs to the Special Issue Advances in Aquaculture Feed Additives)
Show Figures

Graphical abstract

54 pages, 2627 KiB  
Review
Calcium Signaling Dynamics in Vascular Cells and Their Dysregulation in Vascular Disease
by Chang Dai and Raouf A. Khalil
Biomolecules 2025, 15(6), 892; https://doi.org/10.3390/biom15060892 - 18 Jun 2025
Viewed by 1262
Abstract
Calcium (Ca2+) signaling is a fundamental regulatory mechanism controlling essential processes in the endothelium, vascular smooth muscle cells (VSMCs), and the extracellular matrix (ECM), including maintaining the endothelial barrier, modulation of vascular tone, and vascular remodeling. Cytosolic free Ca2+ concentration [...] Read more.
Calcium (Ca2+) signaling is a fundamental regulatory mechanism controlling essential processes in the endothelium, vascular smooth muscle cells (VSMCs), and the extracellular matrix (ECM), including maintaining the endothelial barrier, modulation of vascular tone, and vascular remodeling. Cytosolic free Ca2+ concentration is tightly regulated by a balance between Ca2+ mobilization mechanisms, including Ca2+ release from the intracellular stores in the sarcoplasmic/endoplasmic reticulum and Ca2+ entry via voltage-dependent, transient-receptor potential, and store-operated Ca2+ channels, and Ca2+ elimination pathways including Ca2+ extrusion by the plasma membrane Ca2+-ATPase and Na+/Ca2+ exchanger and Ca2+ re-uptake by the sarco(endo)plasmic reticulum Ca2+-ATPase and the mitochondria. Some cell membranes/organelles are multifunctional and have both Ca2+ mobilization and Ca2+ removal pathways. Also, the individual Ca2+ handling pathways could be integrated to function in a regenerative, capacitative, cooperative, bidirectional, or reciprocal feed-forward or feed-back manner. Disruption of these pathways causes dysregulation of the Ca2+ signaling dynamics and leads to pathological cardiovascular conditions such as hypertension, coronary artery disease, atherosclerosis, and vascular calcification. In the endothelium, dysregulated Ca2+ signaling impairs nitric oxide production, reduces vasodilatory capacity, and increases vascular permeability. In VSMCs, Ca2+-dependent phosphorylation of the myosin light chain and Ca2+ sensitization by protein kinase-C (PKC) and Rho-kinase (ROCK) increase vascular tone and could lead to increased blood pressure and hypertension. Ca2+ activation of matrix metalloproteinases causes collagen/elastin imbalance and promotes vascular remodeling. Ca2+-dependent immune cell activation, leukocyte infiltration, and cholesterol accumulation by macrophages promote foam cell formation and atherosclerotic plaque progression. Chronic increases in VSMCs Ca2+ promote phenotypic switching to mesenchymal cells and osteogenic transformation and thereby accelerate vascular calcification and plaque instability. Emerging therapeutic strategies targeting these Ca2+-dependent mechanisms, including Ca2+ channel blockers and PKC and ROCK inhibitors, hold promise for restoring Ca2+ homeostasis and mitigating vascular disease progression. Full article
(This article belongs to the Special Issue Calcium Signaling in Cell Function and Dysfunction)
Show Figures

Figure 1

23 pages, 858 KiB  
Article
An Adapted Cardioprotective Diet with or Without Phytosterol and/or Krill Oil Supplementation in Familial Hypercholesterolemia: Results of a Pilot Randomized Clinical Trial
by Erlon Oliveira de Abreu-Silva, Rachel Helena Vieira Machado, Bianca Rodrigues dos Santos, Flávia Cristina Soares Kojima, Renato Hideo Nakagawa Santos, Karina do Lago Negrelli, Letícia Barbante Rodrigues, Pedro Gabriel Melo de Barros e Silva, Andressa Gusmão de Lima, João Gabriel Sanchez, Fernanda Jafet El Khouri, Ângela Cristine Bersch-Ferreira, Adriana Bastos Carvalho, Thaís Martins de Oliveira, Maria Cristina Izar, Geni Rodrigues Sampaio, Nágila Raquel Teixeira Damasceno, Marcelo Macedo Rogero, Elizabeth Aparecida Ferraz da Silva Torres, Flávia De Conti Cartolano, Julia Pinheiro Krey, Patrícia Vieira de Luca, Cristiane Kovacs Amaral, Elisa Maia dos Santos, Rodrigo Morel Vieira de Melo, Eduardo Gomes Lima, André de Luca dos Santos, Thiago Gomes Heck, Ana Paula Perillo Ferreira Carvalho, Silvia Bueno Garofallo, Alexandre Biasi Cavalcanti and Aline Marcadentiadd Show full author list remove Hide full author list
Nutrients 2025, 17(12), 2008; https://doi.org/10.3390/nu17122008 - 15 Jun 2025
Viewed by 1188
Abstract
Background/Objectives: Familial hypercholesterolemia (FH) is an increasingly common inherited disorder that increases cardiovascular risk. Despite the importance of lifestyle interventions, adherence to a healthy diet among individuals with FH remains suboptimal. This pilot, multicenter, double-blind, placebo-controlled randomized trial aimed to evaluate the feasibility [...] Read more.
Background/Objectives: Familial hypercholesterolemia (FH) is an increasingly common inherited disorder that increases cardiovascular risk. Despite the importance of lifestyle interventions, adherence to a healthy diet among individuals with FH remains suboptimal. This pilot, multicenter, double-blind, placebo-controlled randomized trial aimed to evaluate the feasibility and preliminary effects of a culturally adapted cardioprotective diet (DICA-FH), alone or in combination with phytosterol and/or krill oil supplementation, on lipid parameters in Brazilian adults with probable or definitive FH. Methods: Between May and August 2023, 58 participants were enrolled across nine Brazilian centers and randomized (1:1:1:1) into four groups: DICA-FH + phytosterol placebo + krill oil placebo; DICA-FH + phytosterol 2 g/day + krill oil placebo; DICA-FH + phytosterol placebo + krill oil 2 g/day; and DICA-FH + phytosterol 2 g/day + krill oil 2 g/day. Interventions lasted 120 days. The primary outcomes were mean low-density lipoprotein cholesterol (LDL-c) and lipoprotein(a) (Lp[a]) levels, as well as adherence to treatment at follow-up. Secondary outcomes included mean levels of other lipids, frequency of adverse events, and assessment of protocol implementation components. All data were presented separately for the allocation groups: phytosterol vs. placebo and krill oil vs. placebo. Results: Mean age was 54.5 ± 13.7 years, and 58.6% were women. Both adherence to protocol (91.8% attendance; 79.1% investigational product intake) and retention (86.2%) were high. No significant differences between groups were found for LDL-c or Lp(a). However, regardless of allocation to active supplementation or placebo, a significant reduction in Lp(a) concentrations was observed following the DICA-FH intervention (median difference: −3.8 mg/dL [interquartile range: −7.5 to −1.2]; p < 0.01). Significant reductions in oxidized LDL (LDL-ox) and LDL-ox/LDL-c ratio were also observed in the overall sample (p < 0.01). Although not statistically significant, all groups showed improvements in diet quality after 120 days. No serious adverse events related to the interventions were reported. Additionally, most protocol implementation components were successfully achieved. Conclusions: The DICA-FH strategy, with or without supplementation, was safe and well-tolerated. Although not powered to detect clinical efficacy (which is acceptable in exploratory pilot trials), the study supports the feasibility of a larger trial and highlights the potential of dietary interventions in the management of HF. Full article
(This article belongs to the Special Issue Lipids and Lipoproteins in Cardiovascular Diseases)
Show Figures

Figure 1

23 pages, 2126 KiB  
Review
Current Insight into Biological Markers of Depressive Disorder in Children and Adolescents: A Narrative Review
by Jana Trebatická, Martin Vatrál, Barbora Katrenčíková, Jana Muchová and Zdeňka Ďuračková
Antioxidants 2025, 14(6), 699; https://doi.org/10.3390/antiox14060699 - 9 Jun 2025
Viewed by 883
Abstract
Depressive disorder (DD) in children and adolescents is a growing public health concern with a complex and multifactorial etiology. While most biomarker research has focused on adults, increasing attention is being paid to age-specific molecular mechanisms. This narrative review provides a comprehensive overview [...] Read more.
Depressive disorder (DD) in children and adolescents is a growing public health concern with a complex and multifactorial etiology. While most biomarker research has focused on adults, increasing attention is being paid to age-specific molecular mechanisms. This narrative review provides a comprehensive overview of current knowledge on potential biomarkers of DD, including genetic, neurotransmitter, hormonal, inflammatory, lipid, and oxidative stress markers, in youth compared to adult populations. Special emphasis is given to findings from the DEPOXIN project (Molecular basis of depressive disorder in children and adolescents, the influence of omega-3 fatty acids and oxidative stress), a multicenter study investigating biological markers in children and adolescents with DD. The project identified significantly increased oxidative stress markers (8-isoprostanes, advanced oxidation protein products, nitrotyrosine) and decreased antioxidant enzyme activity (glutathione peroxidase). Moreover, HDL (high density lipoproteins) cholesterol and its subfractions were negatively correlated with depression severity. At the same time, thromboxane B2, omega-6/omega-3 fatty acid ratios, and salivary cortisol levels showed strong positive correlations with depressive symptoms and biochemical markers of inflammation. These results suggest a distinct molecular profile of depression in paediatric populations, emphasizing the importance of developmental context in biomarker research. The review aims to synthesize existing evidence, compare findings across age groups, and highlight the need for personalized, age-appropriate strategies in the diagnosis and treatment of depressive disorders. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
Show Figures

Graphical abstract

25 pages, 6477 KiB  
Article
Endarachne binghamiae Ameliorates Hepatic Steatosis, Obesity, and Blood Glucose via Modulation of Metabolic Pathways and Oxidative Stress
by Sang-Seop Lee, Sang-Hoon Lee, So-Yeon Kim, Ga-Young Lee, Seung-Yun Han, Bong-Ho Lee and Yung-Choon Yoo
Int. J. Mol. Sci. 2025, 26(11), 5103; https://doi.org/10.3390/ijms26115103 - 26 May 2025
Viewed by 776
Abstract
Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are major contributors to the rise in metabolic disorders, particularly in developed countries. Despite the need for effective therapies, natural product-based interventions remain underexplored. This study investigated the therapeutic effects of Endarachne binghamiae, a [...] Read more.
Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are major contributors to the rise in metabolic disorders, particularly in developed countries. Despite the need for effective therapies, natural product-based interventions remain underexplored. This study investigated the therapeutic effects of Endarachne binghamiae, a type of brown algae, hot water extract (EB-WE) in ameliorating obesity and MASLD using high-fat diet (HFD)-induced ICR mice for an acute obesity model (4-week HFD feeding) and C57BL/6 mice for a long-term MASLD model (12-week HFD feeding). EB-WE administration significantly reduced body and organ weights and improved serum lipid markers, such as triglycerides (TG), total cholesterol (T-CHO), HDL (high-density lipoprotein), LDL (low-density lipoprotein), adiponectin, and apolipoprotein A1 (ApoA1). mRNA expression analysis of liver and skeletal muscle tissues revealed that EB-WE upregulated Ampkα and Cpt1 while downregulating Cebpα and Srebp1, suppressing lipogenic signaling. Additionally, EB-WE activated brown adipose tissue through Pgc1α and Ucp1, contributing to fatty liver alleviation. Western blot analysis of liver tissues demonstrated that EB-WE enhanced AMPK phosphorylation and modulated lipid metabolism by upregulating PGC-1α and UCP-1 and downregulating PPAR-γ, C/EBP-α, and FABP4 proteins. It also reduced oxidation markers, such as OxLDL (oxidized low-density lipoprotein) and ApoB (apolipoprotein B), while increasing ApoA1 levels. EB-WE suppressed lipid peroxidation by modulating oxidative stress markers, such as SOD (superoxide dismutase), CAT (catalase), GSH (glutathione), and MDA (malondialdehyde), in liver tissues. Furthermore, EB-WE regulated the glucose regulatory pathway in the liver and muscle by inhibiting the expression of Sirt1, Sirt4, Glut2, and Glut4 while increasing the expression of Nrf2 and Ho1. Tentative liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis for EB-WE identified bioactive compounds, such as pyropheophorbide A and digiprolactone, which are known to have antioxidant or metabolic regulatory activities. These findings suggest that EB-WE improves obesity and MASLD through regulation of metabolic pathways, glucose homeostasis, and antioxidant activity, making it a promising candidate for natural product-based functional foods and pharmaceuticals targeting metabolic diseases. Full article
(This article belongs to the Special Issue Advances and Emerging Trends in Marine Natural Products)
Show Figures

Figure 1

15 pages, 5624 KiB  
Article
The Activity of Phytotherapic Extracts Combined in a Unique Formulation Alleviates Oxidative Stress and Protects Mitochondria Against Atorvastatin-Induced Cardiomyopathy
by Maria Gemma Nasoni, Serena Benedetti, Erik Bargagni, Sabrina Burattini, Riham Osman, Michela Battistelli and Francesca Luchetti
Int. J. Mol. Sci. 2025, 26(10), 4917; https://doi.org/10.3390/ijms26104917 - 20 May 2025
Viewed by 411
Abstract
Statins, in addition to their main beneficial lipid-lowering effects (lowering cholesterol and LDL levels), have many additional adverse effects. Among them, the most common is skeletal myopathy. Mitochondria not only play a pivotal role in statin-induced adverse skeletal muscle effects but also seem [...] Read more.
Statins, in addition to their main beneficial lipid-lowering effects (lowering cholesterol and LDL levels), have many additional adverse effects. Among them, the most common is skeletal myopathy. Mitochondria not only play a pivotal role in statin-induced adverse skeletal muscle effects but also seem to be involved in the adverse effects of statins on human cardiac function. However, given that similar oxidative phosphorylation pathways are relevant in skeletal and cardiac muscles, whether long-term statin treatment may alter cardiac muscle is currently unknown. Natural products have been widely employed in skeletal muscle disorders thanks to their antioxidant and anti-inflammatory properties. The purpose of this study was to evaluate the effects of a novel phytotherapic formulation (PF) composed of Curcuma and Boswellia essential oils, Harpagophytum procumbens root, and Bromelain on the human AC16 cell line in an in vitro model of atorvastatin-induced cardiomyopathy. Our results showed that atorvastatin decreased cell viability by approximately 50% and induced ROS production and mitochondrial structural damage. Interestingly, supplementation of cells with PF reduced oxidative stress by 20%, improved mitochondrial reshape and function, and restored the expression of the Nrf2/HO-1/GPX4 axis. These results provide new insights into statin-induced cardiomyopathy and suggest the employment of PF as a promising agent in the recovery of cardiac function. Full article
(This article belongs to the Special Issue Targeting Oxidative Stress for Disease: 2nd Edition)
Show Figures

Graphical abstract

17 pages, 1540 KiB  
Article
Effects of Grape Seed Proanthocyanidins on Growth Performance, Jejunal Antioxidant Capacity, Gut Microbial Diversity, and Metabolites in Kangle Chickens
by Qianqian Wang, Qingcan Fan, Xue Yang, Wei Hu, Lucheng Zheng, Lijun Zhou, Jinmeng Shi, Xingxu Zhao and Yong Zhang
Animals 2025, 15(10), 1481; https://doi.org/10.3390/ani15101481 - 20 May 2025
Viewed by 443
Abstract
This study examined the effects of dietary supplementation with grape seed proanthocyanidins (GSPs) on the growth performance, serum biochemistry, jejunal antioxidant capacity, and jejunal microbiota and metabolites in Chinese indigenous Kangle chicken. In this experiment, 120 female Kangle chickens aged 30 days old [...] Read more.
This study examined the effects of dietary supplementation with grape seed proanthocyanidins (GSPs) on the growth performance, serum biochemistry, jejunal antioxidant capacity, and jejunal microbiota and metabolites in Chinese indigenous Kangle chicken. In this experiment, 120 female Kangle chickens aged 30 days old were randomly allocated into three treatment groups: a control group (CON) fed a standard diet and two experimental groups fed diets supplemented with 200 mg/kg (LGSP) or 400 mg/kg (HGSP) of GSPs. The experiment consisted of a 7-day adaptation period followed by a 30-day feeding trial. The results demonstrated that GSP supplementation did not significantly improve their average daily gain or feed efficiency. However, the HGSP group showed significant improvements in their liver and jejunal indices, a reduced jejunal crypt depth, and increased villus-height-to-crypt-depth ratios compared to these values in the CON group. Furthermore, the HGSP group also exhibited elevated concentrations of cholesterol in their serum. Additionally, the oxidative stress levels were probably reduced in the jejuna of the HGSP group, as evidenced by reduced malondialdehyde (MDA) contents. Although jejunal microbial diversity remained unchanged, the metabolomic analysis identified significant upregulation of jejunal metabolites, particularly those associated with free radical scavenging, protein nutrition, and bile acid metabolism, which would be beneficial for maintaining intestinal health. These findings indicate that supplementing their diet with 400 mg/kg of GSPs could improve the health of Kangle chickens, underscoring their potential as a functional feed additive in the production of indigenous Chinese chickens. Full article
(This article belongs to the Collection Comparative Animal Nutrition and Metabolism)
Show Figures

Figure 1

Back to TopTop