Search Results (12,305)

Environmental exposure to heavy metals, particularly cadmium (Cd), has been increasingly associated with obesity, metabolic dysfunction, chronic inflammation, and related disorders such as type 2 diabetes and cardiovascular diseases. Adipose tissue (AT), a paracrine and endocrine organ central to systemic energy and inflammatory homeostasis, is a major site of heavy metal accumulation and a key target of Cd toxicity. However, the mechanisms by which Cd disrupts adipocyte function, especially through epigenetic pathways, remain poorly understood. In this study, we investigated the effects of Cd on epigenetic regulators, antioxidant enzyme activity, inflammatory mediators, and adipogenic programming in human adipose-derived stromal/stem cells (hASCs) and differentiated adipocytes. Cd exposure altered histone modifiers associated with lysine 27 of histone 3 (H3K27), disrupted redox balance in a concentration-dependent manner, impaired adipogenic differentiation and lipid accumulation, and modulated inflammatory and adipokine responses according to differentiation stage and Cd concentration. Our findings suggest that Cd compromises adipose cell homeostasis through mechanisms involving epigenetic dysregulation, oxidative stress imbalance, and altered adipogenic and inflammatory signalling. These observations point to possible long-term metabolic consequences of environmental Cd exposure due to its accumulation in adipose tissue. Full article

Aqueous zinc-ion batteries (AZIBs) are promising for large-scale grid storage due to inherent safety, low cost, environmental compatibility, high theoretical capacity (820 mAhg⁻¹), and suitable redox potential (−0.763 V vs. SHE). However, practical deployment is hindered by coupled challenges at the zinc anode–hydrogen evolution, dendrite growth, and corrosion/passivation, which severely limit cycle life and coulombic efficiency. This review systematically summarizes key advances in AZIB research. It first elucidates working principles and four cathode energy storage mechanisms: Zn²⁺ insertion/extraction, H⁺/Zn²⁺ co-insertion, chemical conversion, and dissolution/deposition. Second, it examines four mainstream cathodes (manganese-based, vanadium-based, Prussian blue analogs, and organic compounds), analyzing performance bottlenecks and corresponding optimization via structural modification. Third, it explores functional mechanisms of advanced separators (polymer, inorganic/ceramic composite, MOF-based, and cellulose-based) in regulating uniform Zn²⁺ deposition and suppressing dendrites. Fourth, it summarizes anode optimization strategies: artificial protective layers for interface stabilization, electrolyte additives to modulate Zn²⁺ solvation/deposition, and 3D porous structures to reduce local current density and provide nucleation sites. Finally, key scientific challenges and future directions are discussed—multi-strategy synergy, in situ characterization, practical battery construction, and sustainable technological development, offering theoretical guidance for advancing AZIBs toward large-scale applications. This review aims to provide a comprehensive perspective spanning from materials to systems, and from mechanisms to applications. Its core objective is not merely to list the types of cathode materials, but to establish a logical bridge directly connecting “key challenges” to “optimization strategies,” with a particular emphasis on the issues and solutions related to the cathode side. Full article

Inflammatory-oxidative stress generated by immune cells plays an important role in aging and in age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Triple-transgenic mice for AD (3xTg-AD) are a suitable model for mimicking this disease in an age-dependent manner. We previously showed that peritoneal leukocyte functions and their redox-inflammatory state are altered early in female 3xTg-AD mice, which exhibit premature aging compared to non-transgenic (NTg) animals. However, their characteristics at 9 months of age, when they present an early neuropathological state, and the sex differences are not known. Here, we analyzed several spleen and thymus leukocyte functions (chemotaxis, natural killer activity, and lymphoproliferation in response to mitogens), pro-inflammatory (IL-1B, TNF-alpha) and anti-inflammatory (IL-10) released cytokine concentrations, and redox parameters (glutathione concentrations and glutathione peroxidase, glutathione reductase, and xanthine oxidase activities) in male and female 3xTg-AD mice compared to age-matched controls. We also analyzed the effects of voluntary physical exercise on immune functions. Our results show that 9-month-old male and female 3xTg-AD mice have worse immune functions, redox state, and inflammation than NTg counterparts. Physical exercise improves immune function. Thus, accelerated aging reflected by peripheral immunosenescence and oxidation-inflammation in 3xTg-AD mice precedes hallmark neuropathology, and exercise can slow down AD progression. Full article

Chronic non-communicable diseases rarely occur in isolation; cardiovascular, metabolic, neurodegenerative, malignant, and age-associated disorders share upstream drivers including oxidative stress, chronic inflammation, mitochondrial dysfunction, and metabolic imbalance. This narrative review synthesizes epidemiological, interventional, and mechanistic studies identified through targeted literature searches to examine redox biology as a shared mechanistic hub linking these conditions. We evaluate antioxidant-rich dietary patterns, selected nutraceuticals, myocardial ischemia–reperfusion injury as a clinical exemplar, rare redox-imbalance disorders as mechanistic stress models, and emerging gene-based reinforcement of endogenous antioxidant systems. Rather than proposing clinical targets, we present an integrative, hypothesis-generating framework illustrating how coordinated lifestyle-driven modulation of redox balance may simultaneously influence multiple disease trajectories. Collectively, the evidence supports a unified redox framework for multi-disease prevention for multi-disease prevention and future intervention design. Full article

Selenium nanoparticles (SeNPs) synthesized through green routes have emerged as promising nanobiostimulants in sustainable agriculture due to their ability to enhance plant growth and antioxidant defense. The aim of this study was to evaluate the biostimulant effect of SeNPs on Capsicum annuum at two stages of crop development to characterize the response to SeNP exposure and identify concentration-dependent effects and application methods. Physiological indicators, including growth, photosynthetic pigment content, and antioxidant activity, were evaluated. Different concentrations of SeNPs were tested during germination, and dosage and two types of application were compared during the vegetative phase in a hydroponic experiment. SeNPs at concentrations of 1.25, 2.5, 5, 10, 20, 40, and 80 µM were applied to chili seeds for 20 days. The plants were exposed to SeNPs concentrations ranging from 1.25 to 80 µM, applied through the roots and leaves. Germination parameters were not significantly affected except for the seed vigor index, which increased at all concentrations, particularly at 20 µM. Low to moderate doses (1.25–20 µM) acted as biostimulants, enhancing plant height, root length, biomass accumulation, photosynthetic pigment content, and phenolic and flavonoid compound synthesis. Conversely, high doses (80 µM) induced phytotoxic effects, especially via root exposure, reflected by growth inhibition, and reduced chlorophyll content. Foliar application demonstrated a systemic biostimulant response, improving root growth and photosynthetic activity without toxicity symptoms. Antioxidant assays (DPPH and ABTS) revealed dose-dependent modulation of redox balance, suggesting adaptive responses to SeNP-induced oxidative conditions. These findings highlight the potential of SeNPs as biostimulants that improve physiological performance in chili plants, while emphasizing the importance of an optimal dosing and application method for sustainable nanotechnology-based crop management. Full article

Hydrogels are widely investigated as drug carriers for cancer therapy due to their ability to provide sustained release and reduce systemic side effects. In this study, MeBSA–PNIPAm hydrogels were developed as dual-temperature and pH-responsive systems for gastrointestinal delivery of 5-FU. MeBSA was successfully synthesized using glycidyl methacrylate and confirmed by FTIR and ¹H-NMR analyses. Hydrogels with varying MeBSA/NIPA ratios were prepared via redox polymerization. DSC results showed that increasing MeBSA content shifted the phase transition temperature of hydrogels, while TGA analysis revealed enhanced thermal stability with higher MeBSA incorporation. Temperature-dependent swelling experiments further demonstrated that the VPTT slightly shifted depending on the surrounding pH, indicating that the thermoresponsive behavior of the hybrid network is influenced by the pH-dependent charge state of the protein component. Swelling studies performed at 30, 37, and 40 °C and at pH 1.2 and 7.4 confirmed dual-responsive behavior. Drug loading efficiencies above 70% were achieved for all formulations. In vitro release studies at 37 °C demonstrated distinct composition-dependent release profiles. During the first 2 h, all hydrogels exhibited controlled and limited release without burst behavior under acidic conditions. Following the transition to pH 7.4, a composition-dependent increase in drug release was observed. GEL 4 achieved the fastest and highest cumulative release (91%), whereas GEL 1 provided the most sustained release over 72 h (32%). Kinetic analysis indicated diffusion-controlled release, best described by the Weibull and Korsmeyer–Peppas models. Cytocompatibility tests showed that fibroblast viability improved with increasing MeBSA content. Overall, protein-modulated dual-responsive hydrogels offer tunable and biocompatible platforms for stimuli-responsive gastrointestinal drug delivery applications. Full article

Graphene and graphene oxide are potential anti-corrosion materials. In this study, epoxy resin/graphene and epoxy resin/graphene oxide composite coatings were succeed prepared. Hydrogen evolution and electrochemical experiments were conducted to determine key parameters—including hydrogen evolution rate, hydrogen evolution volume, corrosion current density, and corrosion potential—of the designed composites in a 3.5 wt.% NaCl solution. The sample with the highest graphene oxide content was 0.8295 μA/cm², representing a two-order-of-magnitude decrease compared to the matrix. Combined with scanning electron microscopy, the surface morphologies of various coatings after corrosion were observed, and the corrosion mechanisms of magnesium alloys with these coatings were carefully discussed. Based on electrochemical analysis, this study proposes and verifies that the working mechanism of the composite coatings relies on a physical barrier rather than a redox reaction. Full article

Liver fibrosis is driven by persistent oxidative stress and inflammatory signaling, with transforming growth factor-β (TGF-β) acting as a key profibrotic mediator. Rutin (Ru) is a plant-derived flavonoid with antioxidant and anti-inflammatory effects, but its low bioavailability limits therapeutic efficacy. This study investigated whether rutin-phytoreduced gold nanoparticles (RuAuNPs) enhanced rutin delivery leading to antifibrotic and anti-inflammatory effects in a rat model of liver fibrosis. Liver fibrosis was induced by oral administration of thioacetamide (TAA, 150 mg/kg body weight, p.o.) for six weeks. Following fibrosis induction, the animals were treated with free rutin (30 mg/kg body weight), RuAuNPs (0.3 mg/kg body weight), or AuNPs (0.3 mg/kg body weight), both expressed as nanoparticle mass, all administered orally for four weeks. RuAuNPs were synthesized by green rutin-mediated reduction and further characterized by TEM, DLS, and FTIR spectroscopy; they were spherical, showing an average hydrodynamic size of 104.1 nm (PDI 0.345). FTIR confirmed rutin capping. Biological effects were evaluated by liver morphology (H&E histology, TEM), biochemical assessment of liver aminotransferases and glico-lipidic status, ELISA and spectrophotometry measurement of redox biomarkers (lipid peroxidation, glutathione status, antioxidant enzymes), cytokines (TNF-α, IL-1β, IL-6), and TGF-β. TAA-induced hepatic injury and remodeling with increased profibrotic signaling, oxidative stress, and inflammation. Free rutin slightly ameliorated the liver damage, whereas RuAuNP improved histological features, reduced TGF-β and pro-inflammatory cytokines, decreased lipid peroxidation, and supported antioxidant defenses. Overall, RuAuNP may enhance rutin efficacy in TAA-induced liver fibrosis, with novelty stemming from the integrated in vivo evaluation of tissue changes and key profibrotic/oxidative/inflammatory pathway. Full article

Background: The potent topoisomerase I inhibitor SN-38, the active metabolite of irinotecan, is limited in clinical application due to severe systemic toxicity. Prodrug strategies enabling selective activation in the tumor microenvironment offer a promising approach to improve its therapeutic index. This study aims to rationally design, synthesize, and systematically evaluate novel disulfide-based SN-38 prodrugs engineered for redox-responsive activation in hypoxic tumors. Methods: Two novel disulfide-based SN-38 prodrugs (SN-38-CSS and SN-38-LSS) were designed and synthesized; SN-38-CSS incorporates a constrained cis-piperazine-fused six-membered cyclic disulfide linker, while SN-38-LSS contains a linear disulfide tether, to differentially exploit the upregulated thioredoxin (Trx/TrxR) system in hypoxic tumor microenvironments. Results: Both prodrugs demonstrated high stability under physiological pH conditions and in human plasma, minimizing premature release. Crucially, they exhibited selective, rapid degradation in the presence of dithiol reductants (TCEP and DTT), mimicking Trx system activity, while remaining stable towards monothiols (GSH, L-Cys). In vitro cytotoxicity assays revealed that the prodrugs exhibited significantly reduced toxicity compared to SN-38 under normoxic conditions across most tested cell lines. However, under hypoxic conditions, their activity was significantly restored. Specifically, SN-38-CSS exhibited cytotoxicity comparable to SN-38 against MCF-7 and NCI-N87 cells, whereas SN-38-LSS showed lower activation efficiency. Conclusions: SN-38-CSS is identified as a promising redox and hypoxia dual-responsive prodrug candidate, highlighting the strategic use of cyclic disulfide linkers for achieving high selectivity and controlled drug release within the tumor microenvironment. Full article

Limosilactobacillus fermentum KUB-D18 is a probiotic strain with significant potential in food fermentation and health promotion, yet the systems-level mechanisms underlying its physiological robustness remain elusive. To elucidate the metabolic remodeling strategies operating across growth phases, we developed an integrated framework combining genome-scale metabolic modeling (GSMM) with transcriptomics. A high-quality metabolic model for L. fermentum KUB-D18, designated iYH640 and comprising 640 genes, 1530 metabolites, and 1922 reactions, was constructed and validated against experimental growth data. Specifically, in vitro assays measuring biomass and glucose concentrations showed a maximum specific growth rate of 0.2696 h⁻¹ and a glucose uptake rate of 11.75 mmol gDCW⁻¹ h⁻¹, providing physiological constraints for the model. Using transcriptome-regulated flux balance analysis (TR-FBA), gene expression profiles from the logarithmic phase (L-phase) and stationary phase (S-phase) were integrated to quantify growth phase-specific metabolic flux distributions. These simulations revealed a distinct transcription-driven metabolic shift, in which the organism moves from a proliferation-oriented metabolic state with active central carbon metabolism and macromolecule synthesis to a maintenance-oriented state. This S-phase is characterized by reduced flux through anabolic pathways together with the selective preservation of redox balance and nucleotide homeostasis. Collectively, these results provide a quantitative explanation of how L. fermentum KUB-D18 balances growth and maintenance, offering a mechanistic basis for improving its stability and functional performance in industrial probiotic applications. Full article

Owing to the synergistic effect of cationic and anionic charge compensation, Li-rich layered oxide cathodes stand as the most promising candidates for next-generation high-energy-density Li-ion batteries. However, the unstable oxygen redox process triggers irreversible oxygen release and structural degradation of the layered framework, which further destabilizes the Li-O-Li configuration and leads to severe performance decay. In this work, a layered/spinel heterostructure coupled with a stabilized Li-O-vacancy configuration is successfully constructed in a Li-rich layered oxide cathode. This design enables outstanding structural and electrochemical stability, delivering an initial discharge capacity of 232 mAh g⁻¹ with a Coulombic efficiency of 90.5%. Moreover, the cathode retains 86.5% of its capacity after 100 cycles. The proposed structural design strategy offers a new pathway toward high-performance Li-rich layered oxide cathodes. Full article

Objective: Emphysema is an important chronic obstructive pulmonary disease (COPD) phenotype characterized by the destruction of air spaces distal to the terminal bronchiole. Aiming to detect potential emphysema biomarkers and to assess the systemic effects of emphysema in blood plasma, we conducted a small cross-sectional shotgun proteomics study. Methods: This study included N = 40 participants divided into four subgroups (N = 10 per group): patients with emphysema and COPD (CE), patients with COPD but without emphysema (CN), healthy smokers (HS) and healthy never-smokers (HN). The participants were sampled non-probabilistically to be similar in terms of age, sex and comorbidities. Participants’ blood plasma was analyzed using liquid chromatography–mass spectrometry. Bioinformatic analysis included detection of differentially expressed proteins (DEPs) and overrepresentation analysis (ORA). Results: Across all groups, a total of 994 proteins were identified, with NADP-dependent malic enzyme (NADP-ME; encoded by ME1) being the only DEP in the CE vs. CN contrast. Proteins such as BMP1, ADAMTSL-2, -4 and IGFBP4, -5, 6 were identified to be upregulated in CE vs. HN. Fibulin-1, -3 and several immunoglobulin components were identified to be downregulated in the CE vs. HN contrast. ORA revealed several enriched processes, including serine-type endopeptidase activity, insulin-like growth factor I and II binding, and signaling receptor binding. Conclusion: We propose NADP-ME, an important enzyme of intermediary metabolism and redox homeostasis, as a potential biomarker candidate of emphysema. Notably, NADP-ME is also implicated in anoikis resistance. Additionally, changes in the expression levels of BMP1, ADAMTSL-2 and -4, and fibulin suggest potential major systemic effects of extracellular matrix perturbation. As all data was derived from LC-MS analysis, these findings need to be further evaluated with complementary methods. Full article

Diabetic cardiomyopathy (DCM) is a distinct myocardial disorder that develops independently of coronary artery disease and hypertension and represents a major contributor to heart failure in patients with diabetes. Beyond hemodynamic alterations, DCM is driven by complex molecular mechanisms involving metabolic dysregulation, mitochondrial dysfunction, inflammation, and fibrotic remodeling. Increasing evidence identifies oxidative stress as a central integrative process linking these pathogenic pathways in the diabetic heart. Chronic hyperglycemia, insulin resistance, and altered substrate utilization promote excessive generation of reactive oxygen species, overwhelming endogenous antioxidant defenses and disrupting myocardial redox homeostasis. Oxidative stress induces direct damage to lipids, proteins, and DNA while simultaneously activating redox-sensitive signaling pathways that amplify inflammation, endothelial dysfunction, cardiomyocyte apoptosis, and fibrosis. In addition, epicardial and visceral adipose tissue have emerged as active contributors to myocardial oxidative stress through paracrine and systemic mechanisms, reinforcing inflammatory and fibrotic crosstalk. This review provides a comprehensive overview of the molecular sources and targets of oxidative damage in DCM, examines the impairment of antioxidant defense systems, and discusses emerging therapeutic strategies aimed at restoring redox balance. Full article

7-ketocholesterol (7-KC) is a bioactive oxysterol generated under oxidative stress and may contribute to bone marrow niche reprogramming in acute myeloid leukemia (AML), thereby promoting stress tolerance and therapeutic resistance Bone marrow mesenchymal stromal cells (MSCs) from healthy donors and AML patients were exposed to subtoxic 7-KC concentrations for 24 h. We evaluated the ABC transporters involved in lipid transport, multidrug resistance and membrane microdomain remodeling; Hedgehog pathway proteins; stress–survival signaling; redox balance by glutathione measurements, and mitochondrial function and dynamics, including membrane potential and gene expression of mitochondrial fission and fusion regulators. Results were integrated using principal component analysis (PCA), heatmaps, and correlation-based networks. Multivariate analyses revealed an integrated, lineage-dependent response. Healthy donor MSCs showed greater plasticity of the efflux and microdomain axis and higher oxidative and mitochondrial vulnerability at high 7-KC doses. AML-MSCs exhibited a basal preconditioned state phenotype and preferentially routed the response toward Hedgehog and stress–survival modules, accompanied by glutathione expansion and adaptive mitochondrial remodeling. 7-KC acts as a broad modulator of several MSC functions, linking sterol homeostasis to Hedgehog signaling, stress–survival pathways, redox balance, and mitochondrial remodeling, potentially supporting a pro-survival, more therapy-tolerant leukemic niche. Full article

Background/Objectives: The aim of the current study was to investigate the mechanistic hepatoprotective efficacy of selenium (SE) and chitosan-coated selenium nanoparticles (CS-SENPs) using a rat model induced by lipopolysaccharide (LPS). Methods: CS-SENP was prepared and characterized for particle size, polydispersity index (PDI), zeta potential, transmission electron microscope (TEM), and Fourier transform infrared spectroscopy (FTIR). Male albino rats (n = 40) were divided into four groups: control, LPS, SE, and CS-SENP. SE and CS-SENPs (5 mg/kg orally for 14 days) were given before LPS injection. Tissue architecture was assessed using histopathological analysis. HSP-47 and STEAP-3 protein expression levels were measured using ELISA, and oxidative stress markers were quantitatively evaluated. The expression of HO-1, TLR-4, STAT-3, TRAF-6, and IL-17A was measured using immunohistochemical analysis. Furthermore, HSP-90 expression was evaluated by immunofluorescence labeling. Results: CS-SENP characterization revealed uniform (PDI = 0.125 ± 0.04) nanoparticle size (108.54 ± 2.24 nm), with high zeta potential (+63.92 ± 6.287 mV), attributed to the CS layer, which was confirmed by FTIR and TEM as an electron-lucent halo enveloping the individual SENP cores. CS-SENPs significantly reduced lipid peroxidation (MDA) and restored glutathione (GSH) more effectively than SE. CS-SENPs improved redox (upregulated HO-1) and iron balance (downregulated STEAP-3), and also increased the anti-inflammatory effect (suppressed TLR-4, IL-17A, TRAF-6, and STAT-3). CS-SENPs showed superior antifibrotic efficacy (suppresses stress proteins, HSP-47 and HSP-90). Rats treated with CS-SENPs had nearly normal liver structure. Conclusions: The results concluded that CS-SENPs had superior and multi-targeted hepatoprotection against LPS-induced liver damage. Full article