Search Results (2,156)

Aging is a complex, universal biological process characterized by the progressive and irreversible decline of physiological functions across multiple organ systems. This deterioration is primarily driven by cumulative cellular damage arising from both intrinsic and extrinsic stressors. The free radical theory of aging, first proposed by Denham Harman in 1956, highlights the role of reactive oxygen species (ROS), byproducts of normal metabolism, in driving oxidative stress and age-related degeneration. Emerging evidence emphasizes the importance of redox imbalance in the onset of neurodegenerative diseases and aging. Among the critical cellular defenses against oxidative stress are sulfur-containing amino acids, namely cysteine (Cys) and selenocysteine (Sec). Cysteine serves as a precursor for glutathione (GSH), a central intracellular antioxidant, while selenocysteine is incorporated into key antioxidant enzymes such as glutathione peroxidases (GPx) and thioredoxin reductases (TrxR). These molecules play pivotal roles in neutralizing ROS and maintaining redox homeostasis. This review aims to provide an updated and critical overview of the role of thiol-containing amino acids, specifically cysteine and selenocysteine, in the regulation of redox homeostasis during aging. Full article

Fibrocapsa japonica (Raphidophyceae) is a cosmopolitan species frequently associated with harmful algal blooms (HABs) and fish mortality events, representing a potential threat to aquaculture and coastal ecosystems. This study provides the first comprehensive morphological, phylogenetic, pigmentary, and toxicological characterization of F. japonica strains isolated from Argentina. Light and transmission electron microscopy confirmed key diagnostic features of the species, including anterior flagella and the conspicuous group of mucocyst in the posterior region. Phylogenetic analysis based on the LSU rDNA D1–D2 region revealed monophyletic relationships with strains from geographically distant regions. Pigment analysis by HPLC identified chlorophyll-a (62.3 pg cell⁻¹) and fucoxanthin (38.4 pg cell⁻¹) as the main dominant pigments. Cytotoxicity assays using RTgill-W1 cells exposed for 2 h to culture supernatants and intracellular extracts showed strain-specific effects. The most toxic strain (LPCc049) reduced gill cell viability down to 53% in the supernatant exposure, while LC₅₀ values ranged from 1.6 × 10⁴ to 4.7 × 10⁵ cells mL⁻¹, depending directly on the strain and treatment type. No brevetoxins (PbTx-1, -2, -3, -6, -7, -8, -9, -10, BTX-B1 and BTX-B2) were detected by LC–MS/MS, suggesting that the cytotoxicity may be linked to the production of reactive oxygen species (ROS), polyunsaturated fatty acids (PUFAs), or hemolytic compounds, as previously hypothesized in the literature. These findings offer novel insights into the toxic potential of F. japonica in South America and underscore the need for further research to elucidate the mechanisms underlying its ichthyotoxic effect. Full article

In this study, we report the development of a novel magnetized coal fly ash-supported nano-silver composite (AgNPs/MCFA) for dual-functional applications in wastewater treatment: the efficient degradation of methyl orange (MO) dye and broad-spectrum antibacterial activity. The composite was synthesized via a facile impregnation–reduction–sintering route, utilizing sodium citrate as both a reducing and stabilizing agent. The AgNPs/MCFA composite was systematically characterized through multiple analytical techniques, including Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and vibrating sample magnetometry (VSM). The results confirmed the uniform dispersion of AgNPs (average size: 13.97 nm) on the MCFA matrix, where the formation of chemical bonds (Ag-O-Si) contributed to the enhanced stability of the material. Under optimized conditions (0.5 g·L⁻¹ AgNO₃, 250 °C sintering temperature, and 2 h sintering time), AgNPs/MCFA exhibited an exceptional catalytic performance, achieving 99.89% MO degradation within 15 min (pseudo-first-order rate constant k_a = 0.3133 min⁻¹) in the presence of NaBH₄. The composite also demonstrated potent antibacterial efficacy against Escherichia coli (MIC = 0.5 mg·mL⁻¹) and Staphylococcus aureus (MIC = 2 mg·mL⁻¹), attributed to membrane disruption, intracellular content leakage, and reactive oxygen species generation. Remarkably, AgNPs/MCFA retained >90% catalytic and antibacterial efficiency after five reuse cycles, enabled by its magnetic recoverability. By repurposing industrial waste (coal fly ash) as a low-cost carrier, this work provides a sustainable strategy to mitigate nanoparticle aggregation and environmental risks while enhancing multifunctional performance in water remediation. Full article

Tellurite (TeO₃²⁻) is a highly soluble and toxic oxyanion that inhibits the growth of Escherichia coli at concentrations as low as ~1 µg/mL. This toxicity has been primarily attributed to the generation of reactive oxygen species (ROS) during its intracellular reduction by thiol-containing molecules and NAD(P)H-dependent enzymes. However, under anaerobic conditions, E. coli exhibits significantly increased tellurite tolerance—up to 100-fold in minimal media—suggesting the involvement of additional, ROS-independent mechanisms. In this study, we combined chemical-genomic screening, untargeted metabolomics, and targeted biochemical assays to investigate the effects of tellurite under both aerobic and anaerobic conditions. Our findings reveal that tellurite perturbs amino acid and nucleotide metabolism, leading to intracellular imbalances that impair protein synthesis. Additionally, tellurite induces notable changes in membrane lipid composition, particularly in phosphatidylethanolamine derivatives, which may influence biophysical properties of the membrane, such as fluidity or curvature. This membrane remodeling could contribute to the increased resistance observed under anaerobic conditions, although direct evidence of altered membrane fluidity remains to be established. Overall, these results demonstrate that tellurite toxicity extends beyond oxidative stress, impacting central metabolic pathways and membrane-associated functions regardless of oxygen availability. Full article

The development of ceria (CeO_2−x)-based nanoantioxidants requires fine-tuning of structural and surface properties for enhancing antioxidant behavior in biological environments. In this contest, here ultrasmall water-dispersible CeO_2−x nanoparticles (NPs), characterized by a high Ce³⁺/Ce⁴⁺ ratio, were synthesized in a non-polar solvent and phase-transfer to an aqueous environment through ligand-exchange reactions using citric acid (CeO_2−x@Cit) and post-treatment with dopamine hydrochloride (CeO_2−x@Dopa). The concept behind this work is to enhance via surface engineering the intrinsic antioxidant properties of CeO_2−x NPs. For this purpose, thanks to electron transfer reactions between dopamine and CeO_2−x, the CeO_2−x@Dopa was obtained, characterized by increased surface Ce³⁺ sites and surface functionalized with polydopamine bearing o-quinone structures as demonstrated by complementary spectroscopic (UV–vis, FT-IR, and XPS) characterizations. To test the antioxidant properties of CeO_2−x NPs, the scavenging activity before and after dopamine treatment against artificial radical 1,1-diphenyl-2-picrylhydrazyl (DPPH^·) and the ability to reduce the reactive oxygen species in Diencephalic Immortalized Type Neural Cell line 1 were evaluated. CeO_2−x@Dopa demonstrated less efficiency in DPPH^· scavenging (%radical scavenging activity 13% versus 42% for CeO_2−x@Cit before dopamine treatment at 33 μM DPPH^· and 0.13 mg/mL loading of NPs), while it markedly reduced intracellular ROS levels (ROS production 35% compared to 66% of CeO_2−x@Cit before dopamine treatment with respect to control—p < 0.001 and p < 0.01, respectively). While steric hindrance from the dopamine-derived polymer layer limited direct electron transfer from CeO_2−x NP surface to DPPH^·, within cells the presence of o-quinone groups contributed with CeO_2−x NPs to break the autoxidation chain of organic substrates, enhancing the antioxidant activity. The functionalization of NPs with o-quinone structures represents a valuable approach to increase the inherent antioxidant properties of CeO_2−x NPs, enhancing their effectiveness in biological systems by promoting additional redox pathways. Full article

Cadmium (Cd)-induced pulmonary toxicity is closely associated with ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxidation (LPO). Luteolin (Lut) is a natural flavonoid compound that exists in many plants. In this study, we used human bronchial epithelial BEAS-2B cells to explore the impact of ferroptosis in the inhibition of Cd-induced BEAS-2B cells proliferation. BEAS-2B cells were exposed to Cd (5 μM) with/without Lut (10 μM), ferroptosis modulators (Ferrostatin-1 (Fer-1)/Erastin), or nuclear factor erythroid 2-related factor 2 (Nrf2) regulators (tert-butylhydroquinone (TBHQ)/ML385). Viability, iron content, reactive oxygen species (ROS), LPO, mitochondrial membrane potential (MMP), and glutathione peroxidase (GSH-PX) activity were assessed. Exposure to Cd significantly decreased cell viability, increased intracellular iron levels, ROS production, and LPO activity, while simultaneously reducing MMP and GSH-PX activity. Fer-1 mitigated Cd-induced cytotoxicity, but Erastin intensified these effects. Mechanistically, Cd exposure suppressed the Nrf2/Solute Carrier Family 7 Member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway, which plays a crucial role in maintaining redox homeostasis. Activation of Nrf2 using TBHQ mitigated oxidative stress and upregulated the expression of key proteins within this pathway, while inhibition of Nrf2 with ML385 exacerbated cellular damage. Notably, Lut treatment could significantly alleviate Cd-induced cytotoxicity, oxidative stress, and downregulation of Nrf2/SLC7A11/GPX4 proteins. These findings demonstrate that ferroptosis is a critical mechanism underlying Cd-mediated lung epithelial injury and identify Lut as a promising therapeutic candidate via its activation of Nrf2-driven antioxidant defense mechanisms. This study provides novel insights into molecular targets for the prevention and treatment of Cd-associated pulmonary disorders. Full article

Background/Objectives: Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, remains a major neglected tropical disease, with over six million cases concentrated, primarily in Latin America. Despite decades of research, treatment continues to rely on two outdated drugs—benznidazole and nifurtimox—both of which exhibit limited efficacy and are associated with severe side effects. In this context, drug repurposing presents a promising strategy to accelerate the development of safer and more effective therapies. Nitroxoline, a hydroxyquinoline compound widely used in Europe to treat bacterial urinary tract infections, has recently garnered attention for its broad-spectrum antimicrobial and anticancer activities. This study evaluated the antitrypanosomal potential of nitroxoline against both epimastigote and intracellular amastigote forms of T. cruzi, demonstrating significantly greater efficacy than benznidazole. Methods: In addition to its antiparasitic activity, we investigated the mechanism of parasite death and found that nitroxoline induces hallmarks of programmed cell death, including chromatin condensation, mitochondrial membrane depolarization, ATP depletion, reactive oxygen species accumulation, and increased membrane permeability. These cellular events are critical for minimizing host tissue inflammation and suggest a safer therapeutic profile. Results: The nitroxoline was shown to induce greater activity than the reference treatment, benznidazole, in addition to triggering events related to apoptotic or silent cell death. Conclusions: Given its established clinical use and favorable safety data, nitroxoline emerges as a strong candidate for further investigation as a repurposed treatment for Chagas disease. Future work should focus on in vivo efficacy, pharmacokinetics, and drug delivery strategies to enhance systemic bioavailability. Full article

In familial Alzheimer’s disease (FAD), presenilin 1 (PSEN1) E280A cholinergic-like neurons (ChLNs) induce aberrant secretion of extracellular amyloid beta (eAβ). How PSEN1 E280A ChLNs-eAβ affects microglial activity is still unknown. We obtained induced microglia-like cells (iMG) from human peripheral blood cells (hPBCs) in a 15-day differentiation process to investigate the effect of bolus addition of Aβ42, PSEN1 E280A cholinergic-like neuron (ChLN)-derived culture supernatants, and PSEN1 E280A ChLNs on wild type (WT) iMG, PSEN1 E280A iMG, and sporadic Alzheimer’s disease (SAD) iMG. We found that WT iMG cells, when challenged with non-cellular (e.g., lipopolysaccharide, LPS) or cellular (e.g., Aβ42, PSEN1 E280A ChLN-derived culture supernatants) microenvironments, closely resemble primary human microglia in terms of morphology (resembling an “amoeboid-like phenotype”), expression of surface markers (Ionized calcium-binding adapter molecule 1, IBA-1; transmembrane protein 119, TMEM119), phagocytic ability (high pHrodo™ Red E. coli BioParticles™ phagocytic activity), immune metabolism (i.e., high generation of reactive oxygen species, ROS), increase in mitochondrial membrane potential (ΔΨm), response to ATP-induced transient intracellular Ca²⁺ influx, cell polarization (cluster of differentiation 68 (CD68)/CD206 ratio: M1 phenotype), cell migration activity according to the scratch wound assay, and especially in their inflammatory response (secretion of cytokine interleukin-6, IL-6; Tumor necrosis factor alpha, TNF-α). We also found that PSEN1 E280A and SAD iMG are physiologically unresponsive to ATP-induced Ca²⁺ influx, have reduced phagocytic activity, and diminished expression of Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) protein, but when co-cultured with PSEN1 E280A ChLNs, iMG shows an increase in pro-inflammatory phenotype (M1) and secretes high levels of cytokines IL-6 and TNF-α. As a result, PSEN1 E280A and SAD iMG induce apoptosis in PSEN1 E280A ChLNs as evidenced by abnormal phosphorylation of protein TAU at residue T205 and cleaved caspase 3 (CC3). Taken together, these results suggest that PSEN1 E280A ChLNs initiate a vicious cycle between damaged neurons and M1 phenotype microglia, resulting in excessive ChLN death. Our findings provide a suitable platform for the exploration of novel therapeutic approaches for the fight against FAD. Full article

Photobiomodulation (PBM) utilizes different wavelengths of light to modulate cellular functions and has emerged as a promising approach in regenerative medicine. In this study, we examined the effects of blue (455 nm), red (660 nm), and near-infrared (810 nm) light, both individually and in combination, on human adipose-derived mesenchymal stem/stromal cells (adMSCs). A single, short-term exposure of adMSCs in suspension to these wavelengths using an integrating sphere revealed distinct wavelength- and dose-dependent cellular responses. Blue light exposure led to a dose-dependent increase in intracellular reactive oxygen species, accompanied by reduced cell proliferation, metabolic activity, interleukin-6/interleukin-8 secretion, and adipogenic differentiation. In contrast, red and near-infrared light preserved cell viability and metabolic function while enhancing cell migration, consistent with their documented ability to stimulate proliferation and mitochondrial activity in mesenchymal stem cells. These findings highlight the necessity of precise wavelength and dosage selection in PBM applications and support the potential of PBM as a customizable tool for optimizing patient-specific regenerative therapies. Full article

Nanoceria is a multifaceted enzyme-like catalyst of ROS-mediated (reactive oxygen species) reactions, which results in its multiple biomedical applications. Biodegradable polysaccharide coatings improve biocompatibility, while the effects of these coatings on the ROS-related activity of nanoceria in cells need thorough studies. Here, we used human embryonic lung fibroblasts to study the effects of maltodextrin and chitosan coatings on cellular oxidative metabolism of nanoceria by examining cell viability, mitochondrial potential, accumulation of nanoparticles in cells, intracellular ROS, expression of NOX4 (NADPH oxidase 4), NRF2 (nuclear factor erythroid 2-related factor 2), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), and STAT3 (signal transducer and activator of transcription 3) proteins as well as the expression of biomarkers of DNA damage/repair, cell proliferation, and autophagy. Both types of polysaccharide-coated nanoceria were non-toxic up to millimolar concentrations. For maltodextrin-coated nano-CeO₂, in contrast to bare nanoparticles, there was no oxidative DNA damage/repair with moderate activation of NOX4 expression. Like bare nanoceria, maltodextrin-coated nanoparticles demonstrate the proliferative impact and do not activate autophagy. However, maltodextrin-coated nanoparticles have an activating impact on mitochondrial potential and the NF-κB pathway. Chitosan-coated nanoceria causes short-term intracellular oxidative stress, activation of the expression of NOX4, STAT3, and NRF2, oxidative DNA damage, and double-strand breaks accompanied by activation of DNA repair systems. In contrast to maltodextrin-coated nanoparticles, chitosan-coated nanoceria inhibits the NF-κB pathway and activates autophagy. These findings would be useful in the development of advanced nanoceria-based pharmaceuticals and contribute to the understanding of the biochemical properties of nanoceria as a modulator of ROS-dependent signaling pathways. Full article

Piperine, a phytochemical alkaloid, exhibits notable anticancer properties in several cancer cell types. In this study, we investigated the mechanisms by which piperine induces cell death and apoptosis in colorectal cancer (CRC) cells, focusing on oxidative stress and key signaling pathways. Using MTT assay, flow cytometry, gene overexpression, and Western blot analysis, we observed that piperine significantly reduced cell viability, triggered G1 phase cell cycle arrest, and promoted apoptosis in DLD-1 cells. In addition, piperine effectively suppressed cell viability and induced apoptosis in other CRC cell lines, including SW480, HT-29, and Caco-2 cells. These effects were associated with increased intracellular reactive oxygen species (ROS) generation, mediated by the regulation of mitochondrial complex III, NADPH oxidase, and xanthine oxidase. Additionally, piperine modulated signaling pathways by inhibiting phosphoinositide 3-kinase (PI3K)/Akt, activating p38 and p-extracellular signal-regulated kinase (ERK). Pretreatment with antimycin A, apocynin, allopurinol, and PD98059, and the overexpression of p-Akt significantly recovered cell viability and reduced apoptosis, confirming the involvement of these pathways. This study is the first to demonstrate piperine induces apoptosis in CRC cells through a multifaceted oxidative stress mechanism and by critically modulating PI3K/Akt and ERK signaling pathways. Full article

Background: To identify drug candidates that reduce cellular stress, linear peptides known as endomorphin (EM) analogs containing proline surrogates in position 2 were tested in in vitro injury models induced by corticosterone (CORT). Methods: In this study, neuroblastoma (SH-SY5Y) cells were treated with CORT and synthesized peptides, and then the cell viability and morphology, reactive oxygen species production (ROS), mitochondrial membrane potential (ΔΨm), adenosine triphosphate (ATP), and intracellular calcium ion [Ca²⁺]_i levels were evaluated. We also conducted an in-depth analysis of the apoptosis markers using quantitative real-time PCR (qPCR). Finally, we explore the brain-derived neurotrophic factor (BDNF) expression (qPCR) and protein levels (ELI-SA and Western blot). Results: The strongest neuroprotective effect in the CORT-induced stress model was shown by peptide 3 and peptide 7 (in the following sequence Tyr-Inp-Trp-Phe-NH2 and Tyr-Inp-Phe-Phe-NH2, respectively). These peptides significantly improved cell viability and reduced oxidative stress in CORT-treated cells. Conclusions: Their neuroprotective potential appears linked to anti-apoptotic effects, along with in-creased BDNF expression. Moreover, in the lipopolysaccharide (LPS)- and interferon-γ (IFN-γ)-induced damage model in macrophage RAW 264.7 cells, these two peptides reduced the secretion of inflammatory mediators nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Peptides exhibiting both neuroprotective and anti-inflammatory properties warrant further investigation as potential therapeutic agents. Full article

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disorder characterized by excessive scarring of lung tissue, predominantly affecting middle-aged and elderly populations. Oxidative stress plays a pivotal role in the pathogenesis of pulmonary fibrosis, disrupting redox homeostasis and driving fibrotic progression. Glutathione reductase (GSR), a key antioxidant enzyme, is essential for maintaining cellular glutathione (GSH) levels and mitigating oxidative damage. However, the specific involvement of GSR in IPF remains poorly understood. This study found that GSR levels were downregulated in IPF patients and mice treated with bleomycin (BLM). GSR knockdown enhanced epithelial-to-mesenchymal transition (EMT) in A549 cells and promoted the activation of MRC5 cells. Additionally, GSR depletion promoted cellular migration and senescence in both A549 and MRC5 cells. Mechanistically, silencing GSR in A549 and MRC5 cells led to a marked reduction in intracellular GSH levels, resulting in elevated reactive oxygen species (ROS) accumulation, thereby promoting the activation of the TGF-β/Smad2 signaling pathway. In conclusion, our findings demonstrate that GSR deficiency aggravates pulmonary fibrosis by impairing antioxidant defense mechanisms, promoting EMT, and activating fibroblasts through the TGF-β/Smad2 signaling. These findings suggest that GSR may be essential in reducing the fibrotic progression of IPF. Full article

Cell adhesion molecules (CAMs) are cell-surface-localized proteins mediating interactions of cells with other cells and the extracellular matrix. CAMs influence cell behavior and survival by inducing various intracellular signaling cascades that regulate diverse cellular processes including cytoskeleton remodeling and gene expression. Here, we review the evidence demonstrating that the levels, subcellular distribution, and binding affinities of CAMs of several major families including integrins, cadherins, immunoglobulin superfamily, and selectins are regulated by intracellularly generated or extracellular reactive oxygen species (ROS). Remarkably, CAMs themselves induce ROS production in response to binding to their ligands by activating lipoxygenases or NADPH oxidases or influencing ROS generation in mitochondria. CAM-dependent ROS production is essential for CAM-mediated cell adhesion and CAM-dependent intracellular signaling. Importantly, CAMs also protect cells from the ROS-induced cell death by stimulating the synthesis of antioxidants and suppressing the cell death signaling. A better understanding of the role ROS play in controlling CAM functions and mechanisms of this control may pave the way to modulating the functions of CAMs in various disorders associated with abnormal cell adhesion. Full article

Secondary iron overload exacerbates osteoporosis by elevating reactive oxygen species (ROS), which suppress osteoblast function and enhance osteoclast activity, disrupting bone remodeling. Reducing iron overload and oxidative stress may improve bone health. Epigallocatechin-3-gallate (EGCG), the main bioactive compound in green tea extract (GTE), is recognized for its antioxidant and iron-chelating properties. This study examined the effect of GTE on bone formation and mineralization in iron-overloaded human osteoblast-like MG-63 cells. An iron-overloaded model was established using ferric ammonium citrate (FAC), followed by treatment with GTE, deferiprone (DFP), or their combination. GTE significantly reduced intracellular iron, ROS levels, and lipid peroxidation while upregulating the osteogenic marker BGLAP, the anti-resorptive marker OPG, and osteogenic mineralization, indicating restored bone health. These results suggest that EGCG-containing GTE mitigates iron-induced oxidative stress and promotes osteogenesis, highlighting its potential as a natural therapeutic supplement for managing iron-overload-associated osteoporosis. Full article