Search Results (780)

Background: Vitamins are micronutrients involved in multiple physiological processes critical for athletic performance. Because athletes are often exposed to increased oxidative stress, higher metabolic turnover, and greater nutritional demands, which can potentially lead to deficiencies in vitamins, understanding vitamin supplementation as a function of sport discipline is of fundamental importance. Methods: This narrative review synthesizes research findings from the past decade, supplemented with earlier studies where necessary, focusing on vitamins A, C, D, E, and the B-complex vitamins. Peer-reviewed literature was evaluated for evidence on the prevalence of deficiencies in athletes, physiological mechanisms, supplementation strategies, and their effects on performance, injury prevention, and recovery. Results: Vitamin D deficiency is highly prevalent among athletes, particularly in indoor sports and during the winter months. Supplementation has been shown to improve musculoskeletal health and potentially reduce injury risk. The antioxidant vitamins C and E can attenuate exercise-induced oxidative stress and muscle damage; however, excessive intake may impair adaptive responses such as mitochondrial biogenesis and protein synthesis. Vitamin A contributes to immune modulation, metabolic regulation, and mitochondrial function, while B-complex vitamins support energy metabolism and red blood cell synthesis. Conclusions: Vitamin supplementation in athletes should be individualized, targeting confirmed deficiencies and tailored to sport-specific demands, age, sex, and training intensity. Dietary optimization should remain the primary strategy, with supplementation serving as an adjunct when intake is insufficient. Further high-quality, sport-specific, and long-term studies are needed to establish clear dosing guidelines and to assess the balance between performance benefits and potential risks associated with over-supplementation. Full article

Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a multifactorial liver disease in which mitochondrial dysfunction, oxidative stress, and inflammation play key roles in driving the progression toward metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC). Dysfunctional mitochondria generate excess reactive oxygen species (ROS), impair antioxidant defenses, activate pro-inflammatory pathways and hepatic stellate cells, and perpetuate liver injury. Mitochondrial Complex I is a major ROS source, particularly under conditions of dysregulated energy metabolism. Since Complex I inhibition by metformin was shown to reduce ROS and activate the adenosine monophosphate-activated protein kinase (AMPK), this study aimed to evaluate whether a novel Complex I Modulator (CIM, BI4500) could attenuate oxidative stress, inflammation, and consequently reduce lipid accumulation and fibrosis in a methionine- and choline-deficient diet (MCD)-fed rat model of MASH. Methods: Rats were fed an MCD or an isocaloric control diet for six weeks. From week four, animals received daily oral treatment with CIM (10 mg/kg) or vehicle (Natrosol). At the endpoint, liver tissue was collected for histological, biochemical, and molecular analyses. Lipid droplet area, inflammatory infiltration, and collagen deposition were evaluated on tissue sections; total lipid content and oxidative stress markers were assessed in homogenates and isolated mitochondria. Molecular pathways related to oxidative stress, lipid metabolism, and fibrosis were assessed at protein and mRNA levels. Results: CIM treatment significantly reduced oxidative stress (ROS, lipid peroxidation, nitrogen species), promoting AMPK activation and metabolic reprogramming. This included increased expression of peroxisome proliferator-activated receptor alpha (PPAR-α) and its target genes, and decreased sterol regulatory element binding protein-1c (SREBP-1c)-driven lipogenesis. These changes halted fibrosis progression, as confirmed by Picro-Sirius Red staining and fibrosis markers. Conclusions: these findings indicate that Complex I modulation may represent a promising strategy to counteract MASLD progression toward MASH. Full article

Mitochondrial dysfunction and oxidative stress are crucial contributors to the pathogenesis of Alzheimer’s disease (AD) and dementia exhibiting cognitive decline at the early stage of neurodegeneration. Natural vitamin antioxidants (NVAs) and novel mitochondria-targeted antioxidants (MTAs) are proposed as potential therapeutics though conclusive evidence is lacking. Objectives were to examine in vivo evidence on NVAs and MTAs for preventing and/or treating cognitive decline leading to dementia, to identify the most promising antioxidants, and highlight translational gaps. Methods followed PRISMA-ScR guidelines. MEDLINE, EMBASE and Scopus were searched for English language in vivo experiments assessing NVAs or MTAs in AD and dementia. A total of 25 studies (13 NVAs; 12 MTAs) met inclusion criteria. NVAs (Vitamin A, B, C, E) demonstrated mixed efficacy in reducing oxidative stress and improving cognitive outcomes, with Vitamin E showing the most consistent neuroprotective effects. MTAs (MitoQ, MitoTEMPO, SS31, SkQ1) improved mitochondrial dynamics and cognitive performance and reduced dementia-related pathology. Both NVAs and MTAs improved biomarker profiles and cognitive outcomes in vivo animal models of AD and dementia, but MTAs showed more robust and consistent efficacy by directly targeting mitochondrial pathways. Given the favourable safety profiles of MTAs in other clinical conditions, early-phase human trials in dementia and AD are warranted to evaluate their long-term cognitive benefits. Full article

Background: Preeclampsia (PE) is a hypertensive disorder of pregnancy associated with oxidative stress and mitochondrial dysfunction. NRF1 and NRF2 are transcription factors that regulate mitochondrial activity and antioxidant defense. This study investigated their expression patterns in placentas from preeclamptic and severe preeclamptic pregnancies by immunohistochemical and bioinformatical methods. Methods: Placentas from 40 healthy controls, 40 PE, and 40 sPE patients were analyzed by histological and immunohistochemical techniques. Protein–protein interaction networks for NRF1, NRF2, and PE-related proteins were constructed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape software, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis performed via ShinyGO, with significance set at false discovery rate (FDR) < 0.05. Results: NRF1 expression was significantly decreased in PE and sPE groups compared to controls, with notably negative staining in syncytial knots and fibrinoid areas. Conversely, NRF2 expression significantly increased, showing intense positivity in syncytiotrophoblasts, stromal cells, and vascular structures. Pathway analysis revealed that decreased NRF1 expression was associated with glutathione metabolism, hypoxia inducible factor-1 (HIF-1) signaling, and AMP-Activated Protein Kinase (AMPK) signaling pathways. Increased NRF2 expression was associated predominantly with inflammatory and immune response pathways, including AGE-RAGE signaling and pathogen–response pathways. Conclusions: Differential expressions of NRF1 and NRF2 in preeclamptic placentas reflect distinct yet interconnected responses to oxidative stress and inflammation. These transcription factors have potential clinical relevance as biomarkers for PE severity assessment and as targets for future therapeutic interventions. Full article

Microalgae are sustainable sources of bioactive compounds with broad hepato-protective potential. This review synthesizes evidence for five major classes—carotenoids such as astaxanthin and fucoxanthin, polysaccharides such as paramylon and fucoidan, phycobiliproteins such as phycocyanin, omega-3 fatty acids, and phenolic extracts—linking their actions to key liver injury mechanisms. Preclinically, these compounds enhance antioxidant defenses, improve mitochondrial function, suppress inflammatory signaling, regulate lipid metabolism, modulate the gut–liver axis, and inhibit hepatic stellate cell activation, thereby attenuating fibrosis. Consistent benefits are observed in models of non-alcoholic and alcoholic fatty liver disease, drug-induced injury, ischemia–reperfusion, and fibrosis, with marked improvements in liver enzymes, oxidative stress, inflammation, steatosis, and collagen deposition. Emerging evidence also highlights their roles in regulating endoplasmic reticulum stress and ferroptosis. Despite their promise, translational challenges include compositional variability, a lack of standardized quality control, limited safety data, and few rigorous human trials. To address these challenges, we propose a framework integrating multi-omics and AI-assisted strain selection with specification-driven quality control and formulation-aware designs—such as lipid carriers for carotenoids or rational combinations like fucoxanthin with low-molecular-weight fucoidan. Future priorities include composition-defined randomized controlled trials in non-alcoholic fatty liver disease, alcoholic liver disease, and drug-induced liver injury; harmonized material specifications; and multi-constituent interventions that synergistically target oxidative, inflammatory, metabolic, and fibrotic pathways. Full article

Mitochondrial dysfunction plays a central role in cardiac aging. Damaged mitochondria release excessive free radicals from the electron transport chain (ETC), leading to an increased production of reactive oxygen species (ROS). The accumulation of ROS, together with impaired ROS clearance mechanisms, results in oxidative stress, further disrupts mitochondrial dynamics, and diminishes bioenergetic capacity. Furthermore, the dysfunctional mitochondria exhibit an impaired endogenous antioxidant system, exacerbating this imbalance. These alterations drive the structural and functional deterioration of the aging heart, positioning mitochondria at the center of mechanisms underlying age-associated cardiovascular decline. In this review, we summarize the current evidence on how mitochondrial oxidative stress, mutations on mitochondrial DNA (mtDNA), and disruptions in the fission—fusion balance contribute to cardiomyocyte aging. This review also explores ways to mitigate oxidative stress, particularly with mitochondria-targeted antioxidants, and discusses the emerging potential of mitochondrial transplantation to replace dysfunctional mitochondria. Full article

Melatonin, an ancient and evolutionarily conserved indolamine, has long attracted attention for its multifunctional roles in redox homeostasis. More recently, it has been studied in relation to immune regulation and cancer biology. Beyond its well-known circadian function, melatonin modulates oxidative stress by directly scavenging reactive oxygen and nitrogen species and by upregulating antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase. At the same time, it exerts wide-ranging immunomodulatory functions by influencing both innate and adaptive immune responses. All these actions converge within the tumor microenvironment, where oxidative stress and immune suppression drive cancer progression. Although the antitumoral effects of melatonin have traditionally been interpreted through its actions on T cells and NK cells, recent studies identify macrophages as an underappreciated and pivotal target. Notably, melatonin influences macrophage polarization, favoring antitumor M1 phenotypes over pro-tumoral M2 states, while attenuating chronic inflammation and restoring mitochondrial function. This review summarizes current knowledge on melatonin’s antioxidant and immunoregulatory mechanisms, highlighting its impact on the tumor immune microenvironment, with a particular focus on the growing recognition of macrophages as a compelling new axis through which melatonin may exert anticancer effects. Full article

Background/Objectives: Infertility is a multifactorial condition with an etiopathology that remains largely unclear. Although substantial evidence implicates oxidative stress (OS) as a key contributor to both male and female infertility, targeted strategies for OS-mediated reproductive dysfunction are still not well defined and require further investigation. Ubiquinol is the reduced form of Coenzyme Q10 involved in mitochondrial bioenergetics. It can be synthesized by humans endogenously or provided by dietary sources—typically egg yolks, oily fish, organ meats, and in smaller amounts in nuts and seeds and leafy green vegetables. The present article reviews possible mechanisms through which Ubiquinol plays a role in the regulation of fertility and reproduction, discussing why it could be positioned as a conditionally essential nutrient. Several questions and areas for further inquiry are also proposed. Methods: The present position paper narratively summarizes evidence related to Ubiquinol fertility and reproduction, focusing on the literature from PubMed, Science Direct, and Semantic Scholar. Results: Research advancements suggest that when physiological demands rise during certain life stages, e.g., the reproductive years, the amount of Ubiquinol produced internally may not be enough to meet heightened needs, particularly with advanced maternal/paternal age. This places a heavier reliance on obtaining Ubiquinol from the diet, thus presenting itself as a conditionally essential nutrient during certain life stages. Conclusions: Overall, Ubiquinol appears to enhance mitochondrial energy production and antioxidant defense in gametes, a process that appears to aid sperm function, oocyte quality, and early embryo development. Collectively, these data indicate a key physiological role for Ubiquinol in male and female fertility, especially given its age-related decline. Full article

Post-oncologic skin is subject to multiple structural and functional impairments following chemotherapy and radiotherapy, including delayed epidermal turnover, compromised barrier integrity, and mitochondrial dysfunction. These changes can lead to persistent dryness, heightened reactivity, impaired regeneration, and reduced patient quality of life. In this context, topical dermocosmetic strategies are essential not only for improving comfort and hydration, but also for supporting key cellular pathways involved in mitochondrial protection and oxidative stress reduction. Despite the promise of natural antioxidant actives, their cutaneous efficacy is often limited by poor stability, low bioavailability, and insufficient penetration of the stratum corneum. The use of nanocarriers promotes deeper skin penetration, protects oxidation-prone antioxidant compounds, and enables a controlled and prolonged release profile. This review summarizes the current evidence (2020–2025) on skin delivery systems designed to enhance the efficacy, stability, and skin penetration of antioxidants. Knowledge gaps and future directions are outlined, highlighting how rationally engineered delivery systems for mitochondria-targeted actives could contribute to safer, more effective strategies for post-oncologic skin regeneration. Full article

Mixed dementia (MD), characterized by overlapping features of Alzheimer’s disease (AD) and vascular dementia (VaD), represents the most prevalent form of late-life cognitive decline. Increasing evidence identifies oxidative stress as a unifying molecular mechanism driving both neurodegenerative and vascular pathologies in MD. Reactive oxygen species (ROS) contribute to amyloid-β aggregation, tau hyperphosphorylation, endothelial dysfunction, and blood–brain barrier disruption, creating a self-perpetuating cycle of neuronal and vascular injury. Mechanistic models demonstrate how chronic hypoperfusion and mitochondrial dysfunction exacerbate ROS generation and neuroinflammation, while impaired Nrf2-mediated antioxidant defense further amplifies damage. Therapeutically, classical antioxidants show inconsistent efficacy, shifting focus toward mitochondrial protection, Nrf2 activation, and lifestyle-based oxidative load reduction. Therefore, we sought to outline therapeutic approaches capable of broadly targeting these mechanisms, through focused narrative analysis of recent studies employing delivery systems for antioxidant proteins and/or redox-regulating miRNAs. In particular, experimental interventions using mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) demonstrate neuroprotective and anti-inflammatory effects via the Nrf2 pathway, suggesting promising avenues for multimodal treatment. Integrating oxidative, vascular, and neurodegenerative paradigms is essential for advancing diagnostic precision and developing targeted interventions capable of addressing the complex pathophysiology of mixed dementia. Full article

Heart failure with preserved ejection fraction (HFpEF) represents a growing clinical challenge, accounting for more than half of all cases of heart failure, for which there are currently no effective treatments. Emerging evidence identifies mitochondrial dysfunction as a central mechanism linking metabolic comorbidities, systemic inflammation, and energy failure in HFpEF. This review provides a comprehensive overview of the metabolic–mitochondrial mechanisms underlying the pathophysiology of HFpEF. Loss of metabolic flexibility, characterized by reduced fatty acid and glucose oxidation, leads to energy inefficiency, lipid accumulation, and oxidative stress. Structural and functional mitochondrial abnormalities, including damaged cristae, altered fission-fusion dynamics, and impaired oxidative phosphorylation, contribute to diastolic dysfunction and ventricular remodeling. In parallel, chronic inflammation and redox imbalance amplify mitochondrial damage through cytokine- and ROS-mediated pathways, creating a cycle of bioenergetic failure. From a therapeutic perspective, strategies aimed at restoring mitochondrial homeostasis, such as physical training, metabolic modulation, SGLT2 inhibition, ketone supplementation, and mitochondria-targeted antioxidants, show promising preclinical results. However, clinical translation remains limited. Deepening the understanding of mitochondrial metabolism could enable the development of personalized treatments capable of improving outcomes for HFpEF patients. Full article

Astaxanthin (AX), a naturally occurring xanthophyll carotenoid, has attracted growing scientific interest due to its potent antioxidant, anti-inflammatory, and metabolic-regulatory properties. This review provides a critical appraisal of the current evidence regarding the nutraceutical potential of AX in muscle metabolism, exercise adaptation, and obesity management. Preclinical and clinical findings indicate that AX enhances lipid utilization, promotes mitochondrial biogenesis through AMPK activation, and improves endurance and muscle strength, particularly among older adults. Moreover, AX mitigates exercise-induced oxidative stress and muscle damage, thereby supporting recovery and physiological adaptation. In obesity models, AX reduces adipose tissue inflammation, improves insulin sensitivity, and modulates adipokine secretion, suggesting a multifaceted role in metabolic syndrome prevention. Despite robust preclinical data, human trials remain limited and often yield inconsistent outcomes, highlighting the need for well-designed, long-term clinical studies. Emerging evidence highlights the importance of optimized delivery strategies to enhance AX bioavailability and mitochondrial targeting. Nanoemulsions, liposomes, and lipid-based carriers improve stability, absorption, and tissue distribution, thereby potentiating AX’s effects on mitochondrial function and exercise adaptation. Overall, AX emerges as a promising nutraceutical candidate for enhancing muscle function, supporting exercise performance, and managing obesity-related metabolic disease, with delivery innovations representing a critical frontier for future translational applications. Full article

High-altitude exposure poses significant health challenges to mountaineers, military personnel, travelers, and indigenous residents. Altitude-related illnesses encompass acute conditions such as acute mountain sickness (AMS), high-altitude pulmonary edema (HAPE), and high-altitude cerebral edema (HACE), and chronic manifestations like chronic mountain sickness (CMS). Hypobaric hypoxia induces oxidative stress and inflammatory cascades, causing alterations in multiple organ systems through co-related amplification mechanisms. Therefore, this review aims to systematically discuss the injury mechanisms and comprehensive intervention strategies involved in high-altitude diseases. In summary, these pathologies involve key damage pathways: oxidative stress activates inflammatory pathways through NF-κB and NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasomes; energy depletion impairs calcium homeostasis, leading to cellular calcium overload; mitochondrial dysfunction amplifies injury through mitochondrial permeability transition pore (mPTP) opening and apoptotic factor release. These mechanisms could be converged in organ-specific patterns—blood–brain barrier disruption in HACE, stress failure in HAPE, and right heart dysfunction in chronic exposure. Promising strategies include multi-level therapeutic approaches targeting oxygenation (supplemental oxygen, acetazolamide), specific pathway modulation (antioxidants, calcium channel blockers, HIF-1α regulators), and damage repair (glucocorticoids). Notably, functional foods show significant therapeutic potential: dietary nitrates (beetroot) enhance oxygen delivery, tea polyphenols and anthocyanins (black goji berry) provide antioxidant effects, and traditional herbal bioactives (astragaloside, ginsenosides) offer multi-targeted organ protection. Full article

Skin aging is driven largely by oxidative stress, chronic inflammation, and mitochondrial dysfunction, processes closely linked to cellular senescence and declining NRF2 activity. Numerous dietary phytochemicals—such as curcumin (from turmeric), resveratrol (from grapes), sulforaphane (from cruciferous vegetables), zerumbone, and salvianolic acid B—abundant in fruits, vegetables, herbs, and traditional food sources, exhibit potent antioxidant and anti-inflammatory properties. This review systematically elucidates the molecular mechanisms by which these compounds mitigate skin aging, primarily through modulating the NRF2 signaling pathway. We further integrate insights from clinical trials of NRF2-targeting agents to inform the translational potential of these dietary bioactives. Molecular docking analyses confirm that these food-derived compounds interact directly with the KEAP1-NRF2 complex, promoting NRF2 activation. Transcriptomic analyses of skin-related datasets (GSE35160, GSE71910, GSE185129) further validate the downregulation of key NRF2-regulated cytoprotective genes (e.g., FTH1, FTL, HMOX1, SLC7A11) involved in antioxidant defense and the suppression of pro-inflammatory mediators. Based on this mechanistic foundation, we discuss the translational potential of these food-derived bioactives and the rationale for their future incorporation into skin-health-promoting nutraceuticals. We highlight how these food-derived phenolics and other bioactives may be incorporated into functional foods or nutraceuticals to support skin health from within, offering a dietary strategy to delay aging. We acknowledge that key translational challenges, such as oral bioavailability and optimal formulation, require further investigation. Further research is warranted to bridge these mechanistic insights into effective human applications. Full article

Objectives: The repurposing of existing drugs as anticancer agents has attracted attention in cancer drug discovery. This study aimed to examine the anticancer efficacy of rosiglitazone (RSG) against cholangiocarcinoma (CCA) and its underlying mechanisms. Methods: The effect of RSG on the viability of KKU-100 CCA cells was examined. The possible molecular targets were identified using proteomic analysis and verified by a series of cell-based assays. Furthermore, the expression of PPARγ protein in CCA tissues was also assessed. Results: RSG exhibited a cytotoxic effect against KKU-100 cells. Proteomic analysis demonstrated a significant different expression protein pattern of the 100 μM RSG-treated group compared to the control group. Significant alteration of several proteins was found, including the up-regulation of calcium-binding, cytoskeletal, and metabolic proteins, concomitant with the down-regulation of antioxidant enzymes. Detailed analyses revealed that RSG induced apoptosis in CCA cells, accompanied by increased caspase 3/7 activities, reactive oxygen species (ROS) generation, and disruption of mitochondrial function. RSG altered the expressions of annexin A1 and antioxidant enzymes, according to Western blot analysis. GW9662, a PPARγ antagonist, did not affect the viability and apoptosis of KKU-100 cells caused by RSG. Immunohistochemistry analysis revealed that PPARγ expression in CCA patients was associated with sex, but not with other common clinicopathological parameters. Its expression did not correlate with patients’ overall survival time. Conclusions: RSG induced apoptotic cell death in CCA cells, which was accompanied by increased ROS levels and impaired antioxidant defense. Its apoptosis-inducing effect is independent of PPARγ activation. These findings underscore the therapeutic potential of RSG for CCA treatment. Full article