Search Results (1,556)

Repeated UV exposure, air pollution, and toxins promote skin oxidative stress. ROS destroy macromolecules, changing cellular mechanisms and signaling cascades. Inflammation and injury to skin cells degrade function and accelerate aging, causing wrinkles, firmness loss, and dermatological disorders. Gymnema inodorum (GI) contains phytochemical antioxidants such polyphenols and triterpenoids that lower ROS and strengthen skin. GI extracts (GIEs) have never been examined for their effects on dermal skin fibroblasts’ oxidative stress and intracellular cytoprotective mechanisms. In this study, GIEs were prepared as a water extract (GIE0) and ethanol extracts with concentrations ranging from 20% to 95% v/v (GIE20, GIE40, GIE60, GIE80, and GIE95). These extracts were assessed for phytochemical content, antioxidant capacity, and free radical scavenging efficacy. The results were compared to a commercially available native Gymnema extract (NGE) obtained from Gymnema sylvestre. During principal component analysis (PCA), the most effective extracts were identified and subsequently evaluated for their ability to mitigate oxidative stress in fibroblasts. Cytoprotective effects of GIE and NGE against H₂O₂-induced human dermal fibroblast injury were investigated by cell viability, intracellular ROS production, and signaling pathways. GIE0, GIE80, GIE95, and NGE were the best antioxidants. By preserving ROS balance and redox homeostasis, GIE and NGE reduce fibroblast inflammation and oxidative stress-induced damage. Decreased ROS levels reduce MAPK/AP-1/NF-κB and PI3K/AKT/NF-κB signaling pathways, diminishing inflammatory cytokines. In conclusion, GIE and NGE have antioxidant and anti-inflammatory capabilities that can reduce H₂O₂-induced fibroblast oxidative stress and damage, thereby preventing skin aging and targeting cancer-associated fibroblasts. Full article

Oxidative stress is a key contributor to retinal degeneration, as the retina is highly metabolically active and exposed to constant light stimulation. This review explores the crucial roles of cysteine and selenocysteine in redox homeostasis and retinal protection. Cysteine, primarily synthesized via the transsulfuration pathway, is the rate-limiting precursor for glutathione (GSH), the most abundant intracellular antioxidant. Selenocysteine enables the enzymatic activity of selenoproteins, particularly glutathione peroxidases (GPXs), which counteract reactive oxygen species (ROS). Experimental evidence from retinal models confirms that depletion of cysteine or selenocysteine results in impaired antioxidant defense and photoreceptor death. Furthermore, dysregulation of these amino acids contributes to the pathogenesis of age-related macular degeneration (AMD), retinitis pigmentosa (RP), and diabetic retinopathy (DR). Therapeutic approaches including N-acetylcysteine, selenium compounds, and gene therapy targeting thioredoxin systems have demonstrated protective effects in preclinical studies. Targeting cysteine and selenocysteine-dependent systems, as well as modulating the KEAP1–NRF2 pathway, may offer promising strategies for managing retinal neurodegeneration. Advancing our understanding of redox mechanisms and their role in retinal cell viability could unlock new precision treatment strategies for retinal diseases. Full article

Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid proliferation, invasiveness, therapeutic resistance, and an immunosuppressive tumor microenvironment. A subpopulation of glial stem-like cells (GSCs) within GBM tumors contributes significantly to tumor initiation, progression, and relapse, displaying remarkable adaptability to oxidative stress and metabolic reprogramming. Recent evidence implicates the atypical kinases RIOK1 and RIOK2 in promoting GBM growth and proliferation through their interaction with oncogenic pathways such as AKT and c-Myc. Concurrently, the redox-sensitive Nrf2/Keap1 axis regulates antioxidant defenses and supports GSC survival and chemoresistance. Additionally, aberrant activation of the canonical Wnt/β-catenin pathway in GSCs enhances their self-renewal, immune evasion, and resistance to standard therapies, particularly under oxidative stress conditions. This review integrates current knowledge on how redox homeostasis and key signaling pathways converge to sustain GSC maintenance and GBM malignancy. Finally, we discuss emerging redox-based therapeutic strategies designed to target GSC resilience, modulate the tumor immune microenvironment, and surmount treatment resistance. Full article

Introduction: Amniotic fluid (AF) plays a pivotal role in foetal gastrointestinal development by delivering bioactive factors that support intestinal maturation. However, the redox environment of AF and its potential contribution to foetal intestinal homeostasis remain insufficiently characterised. This study aimed to quantify key antioxidant markers—superoxide dismutase isoforms (SOD1, SOD3), glutathione (GSH), and the oxidative DNA damage marker 8-hydroxy-2-deoxyguanosine (8-OHdG)—in AF across gestational ages and compare them with those in human milk (HM). Methods: AF samples (n = 60) were collected from pregnancies between 15 and 40 weeks of gestation, grouped into preterm (<37 weeks) and term (≥37 weeks). SOD1, SOD3, GSH, and 8-OHdG concentrations were quantified using ELISA. HM samples (n = 45) were similarly analysed. Results: SOD1 and SOD3 in AF concentrations decreased significantly with gestational age (GA) (p < 0.001), while 8-OHdG levels increased (p < 0.001). SOD3 showed a negative correlation with 8-OHdG (p = 0.004). HM contained significantly higher levels of both SOD isoforms compared to AF (AF vs. HM: 35.6 (1.9–172.3) vs. 267.9 (54.6–843.8), p < 0.001 for SOD1 and 1.2 ng/mL (0.1–26.5) vs. 5.5 ng/mL (0.1–300.0), p < 0.001 for SOD3), regardless of GA. Conclusions: Our findings highlight the dynamic nature of the redox environment in AF and its potential importance for foetal GIT development. The disruption of redox balance by preterm birth or inadequate AF intake during foetal life may have long-term consequences for intestinal development and function. These insights provide a foundation for future clinical studies aimed at enhancing neonatal feeding regimens, particularly for preterm infants and those with congenital gastrointestinal disorders. Full article

Angiogenesis, the formation of new blood vessels from pre-existing ones, is crucial for various physiological and pathological conditions, including embryonic development, wound healing, tissue regeneration and tumor progression. While traditionally attributed to the actions of growth factors and their receptors, emerging evidence highlights the crucial regulatory roles of mitochondria in angiogenesis. This narrative review explores the multifaceted functions of mitochondria in endothelial cells, which are central to blood vessel formation. Beyond their classical role in ATP production, mitochondria contribute to angiogenesis through redox signaling, calcium homeostasis, biosynthetic activity, and reactive oxygen species (ROS) generation. These organelles help regulate key endothelial behaviors such as proliferation, migration, and tube formation through mechanisms that include mitochondrial calcium signaling and ROS-mediated stabilization of hypoxia-inducible factor-1α (HIF-1α), leading to increased vascular endothelial growth factor (VEGF) expression. Additionally, mitochondrial dynamics, dysfunction, and genetic factors are discussed for their influence on angiogenic outcomes. Understanding these complex mitochondrial functions opens new therapeutic avenues for modulating angiogenesis in diseases such as cancer and cardiovascular disorders. Full article

Cellular senescence can occur with similar phenotypes in normal cells, during aging, and in tumor cells, spontaneously or after cytostasis. The fall or increase in proliferative activity are key aspects of the respective conditions, in which the levels of reactive oxygen species can vary, affecting the cellular redox homeostasis. This work aimed to study the relationships between senescence and transformation by comparing cells with different proliferative activities and phenotypes attributable to transformation (NIHs cultures) or senescence (NIHv cultures), before and after incubation with hydrogen peroxide. Both cultures were derived from the NIH/3T3 cell line, which was used here as a reference (NIHb), after the serum starvation. Our experimental model can be representative of the heterogeneity of cell subpopulations, with different degrees of transformation and senescence, found in some tumors. The characterization of the functional properties of NIHb, NIHs, and NIHv cells was performed by a morphocytometric analysis of the cell cycle progression, mitochondrial and lysosomal content/activity, and superoxide anion production. The efficiency of the lysosomal compartment was also assessed by estimating the autophagic activity and measuring lipofuscin autofluorescence. Comparisons of nuclear and cytoplasmic parameters before and after the incubation with hydrogen peroxide revealed differences in the expression and modulation of cellular senescence patterns. The treatment effects were very limited in the NIHb culture; the senescence condition was essentially maintained in the NIHv cells, while the most relevant changes were found in the NIHs cells. In the latter, the acquisition of the senescent phenotype, also demonstrated by the positivity of SA-β-galactosidase, was correlated with a decrease in proliferative activity and a change in the content/activity of the mitochondria and lysosomes, which showed similarities with the basal senescence conditions of NIHv cells. In NIHs cells, increased autophagy events and lipofuscin accumulation also indicate the establishment of cytoplasmic dynamics typical of senescence. The variable responses to hydrogen peroxide, besides depending on the different basal cytokinetic activity of the cultures examined, appeared to be related to the specific cell redox state resulting from the balance between endogenous ROS and those produced after treatment. Especially in NIHs cells, the slowing down of the cell cycle was linked to dynamic interconnections between the mitochondrial and lysosomal compartments. This would indicate that transformed cells, such as NIHs, may express morpho-functional aspects and markers typical of cellular senescence, as a consequence of the modulation of their redox state. Full article

Reactive oxygen species (ROS) act as double-edged swords in cancer biology—facilitating tumor growth, survival, and metastasis at moderate levels while inducing oxidative damage and cell death when exceeding cellular buffering capacity. To survive under chronic oxidative stress, cancer cells rely on robust antioxidant systems such as the glutathione (GSH) and thioredoxin (Trx), and superoxide dismutases (SODs). These systems maintain redox homeostasis and sustain ROS-sensitive signaling pathways including MAPK/ERK, PI3K/Akt/mTOR, NF-κB, STAT3, and HIF-1α. Targeting the antioxidant defense mechanisms of cancer cells has emerged as a promising therapeutic strategy. Inhibiting the glutathione system induces ferroptosis, a non-apoptotic form of cell death driven by lipid peroxidation, with compounds like withaferin A and altretamine showing strong preclinical activity. Disruption of the Trx system by agents such as PX-12 and dimethyl fumarate (DMF) impairs redox-sensitive survival signaling. Trx reductase inhibition by auranofin or mitomycin C further destabilizes redox balance, promoting mitochondrial dysfunction and apoptosis. SOD1 inhibitors, including ATN-224 and disulfiram, selectively enhance oxidative stress in tumor cells and are currently being tested in clinical trials. Mounting preclinical and clinical evidence supports redox modulation as a cancer-selective vulnerability. Pharmacologically tipping the redox balance beyond the threshold of cellular tolerance offers a rational and potentially powerful approach to eliminate malignant cells while sparing healthy tissue, highlighting novel strategies for targeted cancer therapy at the interface of redox biology and oncology. Full article

Plants must contend with oxidative stress, a paradoxical phenomenon in which reactive oxygen species (ROS) can cause cellular damage while also serving as key signaling molecules. Environmental stressors, such as drought, salinity, and temperature extremes, promote ROS accumulation, affecting plant growth and productivity. To maintain redox homeostasis, plants rely on antioxidant systems comprising enzymatic defenses, such as superoxide dismutase, catalase, and ascorbate peroxidase, and non-enzymatic molecules, including ascorbate, glutathione, flavonoids, and emerging compounds such as proline and nano-silicon. This review provides an integrated overview of antioxidant responses and their modulation through recent biotechnological advances, emphasizing the role of emerging technologies in advancing our understanding of redox regulation and translating molecular insights into stress-resilient phenotypes. Omics approaches have enabled the identification of redox-related genes, while genome editing tools, particularly those based on clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins, offer opportunities for precise functional manipulation. Artificial intelligence and systems biology are accelerating the discovery of regulatory modules and enabling predictive modeling of antioxidant networks. We also highlight the contribution of synthetic biology to the development of stress-responsive gene circuits and address current regulatory and ethical considerations. Overall, this review aims to provide a comprehensive perspective on molecular, biochemical, and technological strategies to enhance oxidative stress tolerance in plants, thereby contributing to sustainable agriculture and food security in a changing climate. Full article

Oxidative and inflammatory stresses contribute to the development of many intestinal pathologies. This study characterized the polyphenolic profile and biological activity of a hydroalcoholic extract obtained from the fruit pulp of Feijoa sellowiana on HT29 intestinal epithelial cells subjected to oxidative (H₂O₂) and inflammatory (cytokines) stress. HPLC-DAD-MS analysis revealed an interesting phenolic composition, rich in hydrolyzable tannins (HHDP-glucose, pedunculagin and other ellagic acid derivatives) and condensed tannins (procyanidin dimers), with a total polyphenol content of 8.07 mg/g GAE. The extract was non-cytotoxic up to 160 µg/mL and exerted a protective effect against the cytokine-induced reduction in cell viability. In vitro assays confirmed its strong antioxidant and scavenging capacity. The scratch assay suggested enhanced cell migration. The extract modulated the activity of key metabolic enzymes restoring glucose-6-phosphate dehydrogenase and enolase activity, while supporting glycolytic flux through pyruvate kinase and lactate dehydrogenase. PCA and Pearson correlation analyses confirmed a treatment-dependent modulation of the metabolic and redox profile, suggesting a regulatory role beyond a mere scavenging effect. These findings highlight the nutraceutical potential of feijoa polyphenols, not only as direct antioxidants but also as modulators of cellular metabolism and redox homeostasis, supporting their application in gastrointestinal disorders with oxidative or inflammatory components. Full article

Red blood cells (RBCs) are uniquely vulnerable to oxidative stress due to their role in O₂ transport and their high content of heme iron and polyunsaturated fatty acids (PUFAs). Despite lacking nuclei and organelles, RBC homeostasis relies on a finely tuned redox system to preserve membrane integrity, cytoskeletal organization, and metabolic function. Impairment of this delicate balance results in a series of oxidative events that ultimately leads to the premature clearance of RBCs from the bloodstream. This review outlines the main oxidative mechanisms that affect RBC at different levels, such as membrane, cytoskeleton, and intracellular environment, with a focus on the molecular targets of reactive species. The role of major antioxidant systems in preventing or reversing redox damage will also be examined, revealing their multiple mechanisms of action ranging from direct ROS scavenging to the enhancement of endogenous antioxidant defense pathways. Redox regulatory mechanisms in RBCs are required to maintain membrane integrity, cytoskeletal organization, and metabolic function. Disruption of these processes causes several oxidative processes that trigger premature RBC removal. Cumulative evidence places oxidative stress at the core of RBC dysfunction in both physiological aging and pathological conditions, including diabetes, inflammatory conditions, and hemolytic disorders. Antioxidant-based strategies, rather than providing generalized protection, should aim to selectively target the specific molecular pathways affected in distinct clinical settings. Full article

The hydrocoral Millepora complanata (fire coral) plays a critical role in reef structure and relies on a symbiotic relationship with Symbiodiniaceae algae. Environmental stressors derived from climate change, such as UV radiation and elevated temperatures, disrupt this symbiosis, leading to bleaching and threatening reef survival. To gain insight into the thermal stress response of this reef-building hydrocoral, this study investigates the proteomic response of M. complanata to bleaching during the 2015–2016 El Niño event. Fragments from non-bleached and bleached colonies of the hydrocoral M. complanata were collected from a coral reef in the Mexican Caribbean, and proteomic extracts were analyzed using nano-liquid chromatography–tandem mass spectrometry (nano-LC-MS/MS). Uni- and multivariate analyses were applied to identify significant differences in protein abundance. A total of 52 proteins showed differential abundance, including 24 that showed increased expression and 28 whose expression decreased in bleached fragments. Differentially abundant proteins were associated with amino acid biosynthesis, carbohydrate metabolism, cytoskeleton organization, DNA repair, extracellular matrix composition, redox homeostasis, and protein modification. These molecular alterations reflect critical physiological adaptations that may influence stress sensitivity or tolerance in hydrocorals. The findings indicate that heat stress induces molecular responses involving protein refolding, enhanced vesicular transport, cytoskeletal reorganization, and modulation of redox activity. This contributes to a deeper understanding of the molecular mechanisms underlying bleaching in reef-building hydrozoans and broadens current knowledge beyond the more extensively studied anthozoan corals. Full article

Chronic venous disease (CVD) and its major manifestation, varicose veins (VV) of the lower limbs, is a common, multifactorial disease that affects a significant percentage of adult and elderly people worldwide. Its prevalence has been constantly increasing with the aging of the population and, particularly, with the obesity pandemic (hence, the term ‘phlebesity’). The major pathophysiological mechanisms that are potentiating each other in a vicious cycle, leading to chronic venous hypertension, are represented by endothelial dysfunction, chronic inflammation, impaired hemodynamics, and venous wall remodeling. Oxidative stress is another pathomechanism responsible for CVD and its complications, with the increased generation of reactive oxygen species and decreased antioxidant defense being reported to contribute to VV formation. Herein, we present evidence for the role of impaired redox homeostasis as pathophysiological mechanism responsible for chronic local and systemic oxidative stress in patients with CVD. Full article

Cellular senescence, a state of permanent cell cycle arrest, represents a double-edged sword in biology—providing tumor-suppressive functions while contributing to tissue degeneration, chronic inflammation, and age-related diseases when senescent cells persist. A key driver of senescence is oxidative stress, primarily mediated by excessive reactive oxygen species that damage mitochondrial DNA, modulate redox-sensitive signaling pathways, and trigger the senescence-associated secretory phenotype. Emerging evidence highlights the pathogenic role of SASP in promoting local inflammation, immune evasion, and senescence propagation. This review explores the intricate interplay between redox imbalance and cellular senescence, emphasizing mitochondrial dysfunction, SASP dynamics, and their implications in aging and cancer. We discuss current senotherapeutic strategies—including senolytics, senomorphics, antioxidants, gene therapy, and immunotherapy—that aim to eliminate or modulate senescent cells to restore tissue homeostasis. Understanding the heterogeneity and context-specific behavior of senescent cells remains crucial for optimizing these therapies. Future research should focus on addressing key knowledge gaps, including the standardization of senescence biomarkers such as circulating miRNAs, refinement of predictive preclinical models, and development of composite clinical endpoints. These efforts are essential to translate mechanistic insights into effective senotherapeutic interventions and enable the safe integration of senescence-targeting strategies into routine clinical practice. Full article

Passiflora edulis propagation relies extensively on grafting, yet the optimization of pruning strategies for scion quality remains empirically guided. This study elucidates the physiological and molecular mechanisms underlying scion quality across five leaf retention treatments (0%, 25%, 50%, 75%, and unpruned control). The 50% partial leaf retention (50% PLR) treatment optimally promoted axillary bud development in passion fruit through coordinated physiological and molecular adaptations. This treatment significantly outperformed other treatments in terms of both bud sprouting rate and growth parameters (including length and diameter). Physiological analyses demonstrated transient auxin accumulation coupled with synchronized antioxidant system activation, maintaining redox homeostasis. Transcriptomic profiling identified upregulation of genes in the auxin signaling pathway and cytokinin activators, while dormancy-related genes were suppressed. These findings establish 50% PLR as an optimal threshold that balances photosynthetic capacity with hormonal regulation, providing a science-based strategy to standardize grafted seedling production, while enhancing scion quality for grafting efficiency. Full article

Oxidative stress (OS), defined as an imbalance between pro-oxidant and antioxidant mechanisms, contributes to DNA and protein oxidation as well as cellular injury, and plays a pivotal role in the pathogenesis of chronic kidney disease (CKD). Peroxiredoxins (PRDXs) are key antioxidant enzymes that regulate intracellular peroxide levels and maintain redox homeostasis. Beyond its renal implications, OS is closely intertwined with hypertension and atherosclerosis, both common comorbidities that accelerate CKD progression. As previously reported, serum concentrations of PRDXs 1-5 may help to differentiate between IgA nephropathy (IgAN), membranous nephropathy (MN), and lupus nephritis (LN). This study aimed to assess the utility of baseline serum PRDX levels in predicting longitudinal changes in kidney function and proteinuria in patients with IgAN, MN, and LN. We analyzed data from 80 patients (IgAN, n = 36; MN, n = 23; LN, n = 21) drawn from an initial cohort of 108 in whom baseline serum concentrations of PRDX 1–5 were measured. Patients were stratified into low, medium, and high PRDX level groups at baseline, and associations between these strata and longitudinal changes in eGFR and proteinuria were assessed over a follow-up period of up to five years. Across all groups, the follow-up eGFR was significantly associated with low baseline serum PRDX 1, 2, 3, and 5 (p = 0.043; p = 0.001; p = 0.036; p = 0.007, respectively). Significant associations were also observed between 24 h follow-up proteinuria and low baseline serum PRDX 2, 3, and 5 (p = 0.025; p = 0.025; p = 0.005, respectively), medium PRDX 4 (p = 0.010), and high PRDX 2 (p = 0.019). No significant associations were found within the study groups; however, these associations were more pronounced in IgAN and MN patients. These findings suggest a potential role for PRDXs in predicting and monitoring CKD progression, especially eGFR decline. Full article