Search Results (20,398)

Background and Objectives: Severe COVID-19 frequently fulfills Sepsis-3 criteria and is characterized by thrombo-inflammation and endothelial injury. We evaluated whether a bedside endothelial activation index (EAI = D-dimer/fibrinogen) identifies biologically distinct phenotypes and relates to interleukin-6 (IL-6) response after therapeutic plasma exchange (TPE), and whether baseline IL-6 predicts a ≥50% IL-6 reduction. Methods: Retrospective single-center ICU cohort of adults with SARS-CoV-2 infection, sepsis-related organ dysfunction, and ≥1 TPE session (n = 51). Patients were stratified by median EAI (low vs. high). Outcomes included peri-procedural biomarker/physiology changes (post–baseline), IL-6 responder status (≥50% reduction), correlations with IL-6 reduction (%), and multivariable predictors of response. Results: Compared with low EAI (n = 25), high EAI (n = 26) had higher baseline D-dimer (6.2 vs. 2.2 µg/mL) and lower fibrinogen (2.9 vs. 7.1 g/L) (both p < 0.001). Low EAI showed larger CRP decreases (ΔCRP −84.0 vs. −2.3 mg/L; p = 0.001) and larger fibrinogen falls (Δ −3.1 vs. −0.4 g/L; p < 0.001), while high EAI had larger D-dimer decreases (Δ −2.5 vs. −0.6 µg/mL; p = 0.004) and a modest SOFA improvement (Δ −0.3 vs. +0.1; p = 0.026). IL-6 responders (n = 20) had higher baseline IL-6 than non-responders (365.2 vs. 47.1 pg/mL; p < 0.001). Baseline IL-6 independently predicted response (per doubling: OR 1.94, 95% CI 1.27–2.95; p = 0.002), while age reduced odds (OR 0.91/year, 95% CI 0.84–0.99; p = 0.032). IL-6 reduction correlated with ΔCRP (ρ = −0.41; p = 0.003) and ΔPaO₂/FiO₂ (ρ = 0.37; p = 0.01). Conclusions: EAI stratifies distinct thrombo-inflammatory patterns around TPE, while baseline IL-6 is the dominant predictor of achieving large IL-6 reductions. To emphasize the novelty and clarify the study objective, this exploratory analysis used a phenotype-stratified framework to test whether a simple bedside endothelial activation index could enrich biological response assessment to adjunctive TPE. The prespecified primary outcome was achievement of a ≥50% IL-6 reduction after completion of the TPE course; secondary outcomes included peri-procedural biomarker, oxygenation, SOFA, and ICU endpoints. Full article

Oxidative stress is no longer viewed as a random imbalance between reactive oxygen species and antioxidants, but as a failure of an integrated redox network that connects metabolism, immunity, and metal homeostasis. Classical markers such as malondialdehyde and 4-hydroxynonenal define oxidative damage, yet they cannot explain how redox adaptation occurs or fails. Over the past decade, the discovery of regulated cell-death pathways (ferroptosis, cuproptosis) and emerging metabolic signals has revealed a new generation of adaptive redox mediators—including itaconate, nitro-fatty acids, reactive sulfur species and succinate—that act as electrophilic or persulfidating regulators rather than passive by-products of oxidation. This review integrates mechanistic, biochemical and clinical evidence to define how these mediators remodel the nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1, nuclear factor kappa-light-chain-enhancer of activated B cells, and hypoxia-inducible factor 1-alpha axes, coordinate lipid–metal–sulfur cross-talk, and shape vulnerability or resistance to ferroptosis and cuproptosis. By combining deep molecular research with translational perspectives, we propose a unifying framework for predictive redox medicine based on composite biomarker panels and AI-assisted phenotyping. Understanding and quantifying these next-generation mediators will open new avenues for precision nutrition, drug development, and disease prevention—transforming oxidative-stress biology from a descriptive field into an actionable platform for human health. Full article

This study presents a comprehensive comparative analysis of the performance, combustion, and emission characteristics of a single-cylinder, four-stroke spark-ignition engine fueled by commercial gasoline and raw biogas enhanced with cerium oxide (CeO₂) nanoparticles. Raw biogas containing 58% methane was tested without carbon dioxide removal to reflect practical rural applications, while CeO₂ nanoparticles were ultrasonically dispersed in the fuel to promote homogeneous suspension and catalytic activity. Experiments were conducted under wide-open and part-throttle conditions across a range of engine speeds, with simultaneous measurement of brake thermal efficiency, brake-specific fuel consumption, volumetric efficiency, in-cylinder pressure, heat release rate, combustion phasing, and regulated emissions. The results showed that while gasoline consistently outperformed biogas in torque and power due to its higher heating value and flame speed, the addition of CeO₂ significantly reduced the performance gap. For the biogas mode, CeO₂ addition increased brake thermal efficiency by up to 5%, lowered brake-specific fuel consumption by up to 8%, and shifted the start of main combustion to earlier crank angles, indicating faster and more complete combustion, particularly at high loads where higher temperatures activate CeO₂’s catalytic behavior. Emission analysis revealed that CeO₂-blended biogas reduced carbon monoxide emissions by approximately 25% and unburned hydrocarbons by up to 55% compared with gasoline, while nitrogen oxide emissions were consistently 15–22% lower. These reductions were observed across both wide-open and part-throttle conditions, confirming improved combustion completeness and lower peak flame temperatures. These improvements are attributed to CeO₂’s oxygen-storage capability, catalytic oxidation activity, and enhanced thermal conductivity, which collectively strengthen combustion completeness and cyclic stability. The findings demonstrate that nanoparticle-enhanced biogas can substantially improve the environmental and operational viability of spark-ignition engines, offering a practical pathway for integrating renewable gaseous fuels into existing transportation systems. Full article

Background/Objectives: Retinoblastoma represents the most common intraocular malignancy in childhood; however, the clinical applicability of mitomycin C (MMC) is restricted by dose-dependent ocular toxicity. Consequently, the development of pharmacological strategies that sensitize tumor cells to MMC while allowing dose reduction remains an unmet therapeutic objective. In this context, quercetin, a bioactive flavonoid with pleiotropic anticancer properties, has emerged as a potential chemosensitizing agent. Methods: Human retinoblastoma cell lines Y79 and WERI-Rb1 were exposed to MMC and quercetin, administered either individually or in fixed-ratio combinations. Cytotoxic responses were quantified through dose–response modeling and IC₅₀ determination following 24 and 48 h of treatment. Drug–drug interactions were quantitatively characterized using the Chou–Talalay combination index (CI) approach and isobologram analysis. Cell cycle distribution was assessed by propidium iodide (PI)-based flow cytometric analysis to evaluate treatment-associated alterations in cell cycle progression. Apoptotic cell death was assessed by Annexin V-FITC/PI flow cytometry, while transcriptional modulation of genes associated with apoptosis, cell cycle regulation, and oxidative stress (BAX, BCL-2, TP53, CASP3, CDKN1A, and HMOX1) was evaluated by qRT-PCR. Modulation of tumor-supportive signaling was examined by measuring VEGF and IL-6 secretion. Translational relevance was further investigated using a three-dimensional (3D) tumor spheroid model, and the functional contribution of reactive oxygen species (ROS) was interrogated through N-acetyl-L-cysteine (NAC) rescue experiments. Results: Quercetin significantly enhanced the cytotoxic activity of MMC in both retinoblastoma cell lines, with CI values below 1 across IC₅₀–IC₉₀ effect levels, indicating a synergistic pharmacological interaction. PI–FACS analysis revealed that combined MMC and quercetin treatment induced a pronounced accumulation of cells in the G2/M phase, consistent with cell cycle arrest, with a more marked effect observed in Y79 cells compared with WERI-Rb1 cells. Combination treatment resulted in a pronounced increase in apoptotic cell populations compared with single-agent exposure and triggered a coordinated pro-apoptotic transcriptional response, characterized by increased expression of BAX, TP53, CASP3, CDKN1A, and HMOX1, alongside suppression of BCL-2 and a marked shift in the BAX/BCL-2 ratio. Concurrently, VEGF and IL-6 secretion were significantly reduced, reflecting attenuation of pro-angiogenic and pro-inflammatory signaling. Notably, synergistic cytotoxicity was maintained in 3D tumor spheroids, where combined treatment induced spheroid shrinkage, architectural disruption, and reduced viability. NAC pretreatment diminished ROS accumulation and partially restored cell viability, indicating that oxidative stress contributes to, but does not solely account for, the observed synergistic cytotoxic effect. Conclusions: Collectively, these findings indicate that quercetin appears to function as an effective chemosensitizing adjuvant to MMC in retinoblastoma models, through transcriptional changes consistent with p53-associated apoptotic signaling at the transcriptional level, G2/M cell cycle arrest, and partial involvement of ROS-related cellular stress responses, along with suppression of tumor-supportive signaling pathways. The preservation of synergistic activity in 3D tumor spheroids supports the potential preclinical relevance of this combination. However, these findings are based on transcriptional and phenotypic analyses and should be interpreted as hypothesis-generating, requiring further validation through protein-level and in vivo studies before translational application. Full article

The global prevalence of osteoporosis is rising, particularly among the elderly and post-menopausal population. Although natural flavonoids can inhibit osteoclast overactivation, their low abundance and extraction challenges limit clinical translation. In this study, we synthesized a flavonoid derivative, SZQ-4, and evaluated its therapeutic potential for post-menopausal osteoporosis (PMO). Using an RANKL-induced osteoclastogenesis model in vitro, we demonstrated through TRAP staining, RT-qPCR, and bone resorption assays that SZQ-4 significantly suppresses osteoclast formation and activity. Mechanistically, RNA-seq, Western blot, siRNA knockdown, and plasmid-based overexpression experiments revealed that SZQ-4 reduces RANKL-induced reactive oxygen species (ROS) production, regulates SIRT3 expression, and improves mitochondrial function, thereby attenuating osteoclast differentiation. In an ovariectomy-induced bone loss mouse model, SZQ-4 treatment markedly alleviated femoral bone loss, decreased osteoclast numbers, and lowered ROS levels in the bone marrow microenvironment. Collectively, our findings indicate that SZQ-4 inhibits osteoclast-driven bone resorption by modulating the ROS-SIRT3–mitochondrial function axis, highlighting its potential as a candidate for preventing pathological bone loss. Full article

Ulcerative colitis (UC) is a multifactorial disease characterized by chronic intestinal inflammation and disrupted oxidative balance, significantly impairing patients’ quality of life. Tannins, a class of polyphenolic compounds widely distributed in plants, have demonstrated notable therapeutic potential against UC due to their inherent antioxidant and anti-inflammatory properties. This study employs a systematic literature review of databases, including PubMed and Web of Science, to investigate the molecular mechanisms by which tannins restore intestinal inflammatory and oxidative homeostasis. The findings indicate that tannins directly scavenge reactive oxygen species (ROS) via their polyphenolic structure, mitigate oxidative damage, upregulate antioxidant enzyme expression, suppress pro-inflammatory cytokine secretion, and preserve intestinal barrier integrity. Despite their significant therapeutic promise, challenges such as low bioavailability and structural complexity remain. Future research should prioritize bioavailability enhancement, clarification of structure-activity relationships, and translational studies to facilitate the clinical application of tannin-based therapies for UC. Full article

This review examines the role of sulfate-reducing bacteria in the anaerobic degradation of hydrocarbons in marine sediments, where they contribute to the mineralization of organic matter under anoxic conditions. The metabolic diversity of these microorganisms is described, including their ability to degrade various classes of hydrocarbons such as short-chain (C₂–C₅), medium-chain (C₆–C₁₂), and long-chain (C₁₃–C₂₀₊) alkanes, alkenes, and aromatic compounds like naphthalene and phenanthrene. The primary mechanisms involved in the initial activation of these hydrocarbons—fumarate addition and carboxylation—are discussed, along with key enzymes, including alkylsuccinate synthase and benzylsuccinate synthase. Syntrophic interactions are also considered, particularly in which archaea initiate the oxidation of short-chain alkanes (e.g., ethane and butane), with sulfate-reducing bacteria serving as terminal electron acceptors via sulfate reduction. The potential application of these anaerobic processes in bioremediation strategies for oil-contaminated marine sediments is discussed. This microbially mediated degradation may offer a complementary approach to aerobic methods, particularly in oxygen-limited environments. Understanding the activity of sulfate-reducing bacteria activity is relevant to several areas: the development of remediation techniques for anoxic zones, the assessment of methane emissions from marine sediments, the management of microbiologically influenced corrosion, and potential biotechnological applications. Current research directions include the study of syntrophic microbial consortia and the exploration of bioelectrochemical systems. Full article

To overcome active site blockage and poor interfacial contact in traditional syntheses, PtNi bimetallic nanoparticles were grown in situ on a microporous carbon paper via pulse electrodeposition. Firstly, the impact of deposition potential was investigated. The results indicate that the deposition potential significantly modulates the surface Pt⁰/Pt²⁺ ratio; concurrently, a shift toward more negative potentials intensified nanoparticle agglomeration. The effects of the duty cycle were investigated at an optimal deposition potential of −0.95 to −0.4 V. A duty cycle of 30% yielded the optimal Pt⁰/Pt²⁺ ratio. Furthermore, TEM revealed a coexisting strain profile of bulk PtNi lattice contraction and localized expansion at peripheral Pt (111) facets. This synergistic tuning of surface valence and strain optimizes the thermodynamic balance between oxygen adsorption and intermediate desorption on Pt sites. In summary, the optimal catalyst, prepared at a deposition potential of −0.95 V and a duty cycle of 30%, showed the best reaction behavior in the oxygen reduction reaction with an initial onset potential of 0.92 V (vs. RHE). After 5000 cycles of testing, the catalyst showed a constant durability, with the onset potential degrading only marginally to 0.87 V. This work successfully demonstrates that the surface morphology and valence states of the catalyst can be effectively tailored by regulating the pulse voltage and duty cycle. Full article

The oxygen evolution reaction (OER), a key half-reaction in electrochemical water splitting, is limited by sluggish multi-electron transfer kinetics, starting extensive research into efficient, low-cost nanoscale electrocatalysts, particularly those based on nickel, cobalt, and iron, as well as mixed-metal, hybrid, and heteroatom-doped carbon-based metal-free systems, as presented here. Ni- and Co-based electrocatalysts show high efficiency for alkaline OER due to optimized nanostructures, surface modifications, heterostructure design, and multi-metal doping, which enhance activity, stability, and electronic properties. Their performance relies on precise atomic-level control of structure and synergistic interactions, enabling them to approach or rival noble-metal catalysts. Iron-based electrocatalysts are also promising due to their abundance, low cost, and flexible redox chemistry, forming active iron oxyhydroxide species during operation; however, their low conductivity requires structural and electronic optimization. Beyond Fe, Ni, and Co, copper-based compounds, zeolitic imidazolate framework-derived structures, and manganese phosphide–cerium oxide composites offer enhanced oxygen vacancies, tunable structures, and strong interfacial synergy. Furthermore, heteroatom-doped carbon materials incorporating nitrogen, phosphorus, or sulfur improve catalytic activity by modifying electronic structure, creating active sites, and enhancing charge transfer. Overall, careful control of composition, structure, and electronic properties enables the development of efficient, durable, and scalable noble-metal-free catalysts for OER. Full article

Hypoxia, a hallmark of hepatocellular carcinoma (HCC), regulates metabolic reprogramming, tumor progression, and therapy resistance. Although hypoxia-induced glycolytic changes are recognized, it remains unclear how intrinsic tumor aggressiveness influences the magnitude and plasticity of metabolic and transcriptional responses to oxygen deprivation. In this study, we investigated the effects of chronic hypoxia (1% O₂ for 48 h) in spheroids generated from two immortalized (HepG2, Hep3B) and two patient-derived HCC cell lines with distinct aggressiveness (HLC19, HLC21). The metabolic activity, energetic status, proliferation, and expression of hypoxia- and metabolism-related genes were assessed, with oxygen levels monitored to validate experimental conditions. It has resulted that immortalized HCC spheroids displayed similar metabolic and transcriptional responses to hypoxia, with enhanced glycolytic activity but limited phenotypic plasticity. Primary HCC spheroids exhibited aggressiveness-dependent differences. Aggressive HLC19 cells showed a pre-established glycolytic phenotype, stable ATP levels, sustained proliferation, and minimal transcriptional remodeling under hypoxia. Less aggressive HLC21 cells relied on the delayed glycolytic activation and induction of hypoxia-responsive genes to maintain viability. Clustering analyses indicated that metabolic strategies, rather than absolute activity, aligned with tumor aggressiveness. These findings suggest that intrinsic tumor aggressiveness shapes hypoxia-driven metabolic programs in HCC and supports the relevance of patient-derived 3D models for studying metabolic adaptation. Full article

Diabetic retinopathy (DR) is a leading cause of vision loss worldwide and represents a complex neurovascular complication of diabetes mellitus driven by chronic hyperglycemia. Increasing evidence identifies oxidative stress—defined as an imbalance between reactive oxygen species (ROS) production and antioxidant defenses—as a central pathogenic mechanism linking metabolic dysregulation to retinal injury. The retina is particularly vulnerable to oxidative damage due to its high metabolic demand, elevated oxygen consumption, and abundance of polyunsaturated fatty acids. Hyperglycemia activates multiple interconnected biochemical pathways, including the polyol and hexosamine pathways, protein kinase C signaling, advanced glycation end-product formation, and lipid peroxidation, all of which converge on excessive ROS production and mitochondrial dysfunction. Growing attention has focused on oxidative stress biomarkers as tools to characterize DR severity and progression. Elevated systemic markers of lipid, protein, and DNA oxidation, together with impaired antioxidant capacity, correlate with disease stage, while oxidative biomarkers detected in aqueous and vitreous humor reflect localized retinal injury. Importantly, oxidative stress biomarkers are also associated with functional outcomes, including best-corrected visual acuity and diabetic macular edema. Integration of systemic and ocular oxidative biomarkers with clinical staging may improve risk stratification and support personalized therapeutic strategies in DR. Full article

This study provides a comparative evaluation of two Salvia species, the widely cultivated Salvia sclarea L. and the comparatively underexplored wild species Salvia pratensis L., integrating phytochemical profiling, chemical safety assessment, and biological activity investigation. Dried hydroethanolic extracts and essential oils obtained from aerial parts were analysed. HPLC–PDA analysis revealed distinct phenolic acid profiles, with S. sclarea characterized by higher levels of rosmarinic and protocatechuic acids, whereas S. pratensis contained greater amounts of hydroxycinnamic acids such as caffeic, p-coumaric, and ferulic acids. The total phenolic content was higher in S. pratensis (79.22 mg GAE/g dry extract) than in S. sclarea (52.50 mg GAE/g). GC–MS analysis showed that the essential oil of S. sclarea was dominated by oxygenated monoterpenes, mainly linalyl acetate and linalool, while S. pratensis exhibited a linalool-rich profile accompanied by sesquiterpene derivatives. Chemical safety assessment indicated minimal contamination, with pesticide residues detected only in S. sclarea at levels below regulatory limits and low concentrations of cadmium and lead in both species. The extracts showed strong antioxidant activity (DPPH IC₅₀ values of 6.67 µg/mL for S. sclarea and 3.16 µg/mL for S. pratensis) and moderate broad-spectrum antimicrobial activity (MIC 312.5–2500 µg/mL). In vitro assays on HEK 293 and HaCaT cells confirmed low cytotoxicity, with no evidence of membrane damage or pro-inflammatory effects. Overall, the results highlight the significant bioactive potential of the less studied S. pratensis, demonstrating that this wild species represents a promising alternative source of natural antioxidant and antimicrobial compounds comparable to the widely cultivated S. sclarea. Full article

Nutrient inputs from human activities, such as agriculture and sewage discharge, influence algal blooms in water bodies. In Ecuador, the Daule River receives wastewater discharges. In addition, poor agricultural practices, including the unsuitable use of fertilisers in combination with soil erosion and surface runoff processes, increase the nutrient load to the river. Considering this, the objective of this study was to evaluate environmental and biological variables using statistical analysis to identify the parameters that influence algal blooms in the main stem of the Daule River. The methodology consisted of two phases: (i) data collection, including water sampling and laboratory work for the analysis of nutrients and phytoplankton, and (ii) statistical analysis, which includes univariate, bivariate, inferential and multivariate analysis (STATICO technique). The results showed that pH and dissolved oxygen were the main drivers of diatoms (Polymyxus coronalis and Aulacoseira granulate) and the charophyte Mougeotia sp. Similarly, ammonium-N was the main driver of the diatom Ulnaria ulna and the cyanobacteria Planktothrix cf. agardhii. The outcomes of this study identified the main environmental variables driving blooms of the five most abundant species, providing a basis for the development of ecological models in the context of land use and climate change. Full article

Nanomaterials (NMs) are increasingly utilized in drug delivery, diagnostic imaging, and therapeutic applications. However, their widespread use raises concerns regarding potential neurotoxicity, particularly for metal and metal oxide nanoparticles. Accumulating evidence indicates that these nanoparticles induce neurotoxicity through interconnected mechanisms, including excessive reactive oxygen species generation, activation of neuroinflammatory pathways, mitochondrial dysfunction, and disruption of blood–brain barrier integrity. These molecular events collectively lead to synaptic impairment, neuronal apoptosis, and progressive cognitive and behavioral deficits, with toxicity severity influenced by dose, exposure duration, and age. Given that in vitro models often fail to capture complex systemic interactions such as nanoparticle biodistribution, blood–brain barrier dynamics, and neuroimmune responses, this review places particular emphasis on in vivo studies to provide a more physiologically relevant understanding of nanoparticle-induced neurotoxicity. Importantly, a growing body of in vivo evidence demonstrates that natural bioactive compounds can mitigate these effects by targeting key pathogenic pathways, including oxidative stress, inflammation, and mitochondrial dysfunction, while preserving neuronal integrity. These findings highlight the therapeutic potential of natural bioactives as protective agents against nanoparticle-induced neurotoxicity and as candidates for broader neuroprotective strategies. This review summarizes the mechanistic basis of metal and metal oxide nanoparticle neurotoxicity and critically evaluates the protective role of natural bioactive compounds, with a focus on evidence derived from animal models. Full article

Water-soluble fullerene derivatives such as fullerenol C₆₀(OH)₂₄ are promising candidates for nanomedicine applications, yet their effects on innate immune cells remain poorly characterized. We investigated the interaction of fullerenol with human neutrophils isolated from healthy donors, exposed to concentrations of 0.25–200 μg/mL over 24–72 h. Using multi-parameter flow cytometry, we assessed viability, apoptosis, phagocytic activity, and intracellular reactive oxygen species (ROS) production, complemented by cell-free DPPH radical scavenging assays. Fullerenol was taken up by neutrophils in a concentration- and time-dependent manner. No significant cytotoxicity was observed up to 100 μg/mL, while viability declined at 200 μg/mL. Phagocytosis of opsonized E. coli was preserved at lower concentrations, though a statistically significant negative correlation with fullerenol concentration was detected at higher doses. In cell-free assays, fullerenol scavenged DPPH radicals with an EC₅₀ of 48.90 ± 10.02 μg/mL, exhibiting slower kinetics than Trolox or ascorbic acid. Critically, fullerenol suppressed intracellular ROS production by >33% at 50 μg/mL following PMA stimulation of neutrophils. These findings demonstrate that fullerenol C₆₀(OH)₂₄ combines potent intracellular antioxidant activity with a favorable neutrophil safety profile, supporting its potential application in oxidative stress-related conditions. Full article