Search Results (440)

Korean native black goat is commonly consumed as thermally processed extracts and is widely perceived to exhibit health-promoting properties; however, the contribution of intrinsic muscle proteins to these functional characteristics remains unclear. This study evaluated the effects of thermal processing on the antioxidant activity of myofibrillar and sarcoplasmic protein fractions using a screening-based approach. Protein fractions were extracted and subjected to various thermal conditions (60–121 °C), followed by analyses of extractable protein, α-amino group content, and antioxidant activities, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, hydroxyl radical scavenging, iron-chelating ability, and ferric reducing antioxidant power (FRAP). Thermal processing increased α-amino group content, particularly in the myofibrillar fraction, indicating enhanced protein degradation. Antioxidant activities improved with increasing temperature, with myofibrillar proteins showing stronger activity than sarcoplasmic proteins. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE) indicated fragmentation in myofibrillar proteins and aggregation in sarcoplasmic proteins. Cluster analysis supported fraction-dependent differences in antioxidant responses. These findings suggest that thermal processing enhances antioxidant activity in a protein fraction-dependent manner and provide practical insights for optimizing processing conditions of Korean native black goat extracts. Full article

Multiple myeloma profoundly remodels the bone marrow microenvironment, causing osteolytic bone disease through a persistent uncoupling of bone resorption and formation. Beyond the canonical roles of the receptor activator of nuclear factor kappa-B ligand/receptor activator of nuclear factor kappa-B/osteoprotegerin triad and Wnt antagonism, three interdependent stress programs orchestrate the osteolytic niche. These include oxidative stress driven by mitochondrial and nicotinamide adenine dinucleotide phosphate oxidase-derived reactive oxygen species; sterile inflammation sustained by damage-associated molecular patterns, pattern-recognition receptors, and pro-inflammatory cytokines; and autophagy–lysosomal remodeling governed by transcription factor EB and the coordinated lysosomal expression and regulation network. These axes intersect with iron handling and lipid peroxidation to regulate sensitivity to ferroptotic cell death, thereby shaping osteoclast priming, osteoblast suppression, and matrix turnover. Building on these mechanistic insights, we outline a translational framework that aligns standardized bone turnover markers of formation and resorption with composite panels of oxidative and nitrosative stress. This framework also integrates modern imaging to capture structural injury and metabolically active marrow disease. We further propose a therapeutic roadmap layered on antiresorptive foundations that targets selective inhibition of nicotinamide adenine dinucleotide phosphate oxidase 4 and calibrated modulation of nuclear factor erythroid 2–related factor 2, disrupts damage-associated molecular pattern and cytokine circuits, and applies lineage- and timing-specific tuning of autophagy together with restoration of ferroportin-1 or iron chelation. This integrated strategy is designed to recouple bone remodeling and improve clinically meaningful skeletal outcomes in multiple myeloma. Full article

Aiming to reduce synthetic fertilizer dependence and enhance soil fertility, this study isolated and characterized nitrogen-fixing bacteria from the maize rhizosphere. Nitrogen-free selective media were used for bacterial isolation, followed by detection of the nifH gene and nitrogenase activity. Phylogenetic identification was conducted via 16S rRNA sequencing. Growth-promoting traits, stress tolerance, and pot-based plant inoculation effects were assessed. Genetic modification of strain GN8811 was performed to improve nitrogen fixation and growth promotion. Seven isolates that carried the nifH gene and exhibited nitrogenase activity were closely related to four genera. Several isolates showed phosphate solubilization, iron chelation, IAA production, or potassium solubilization, with GN2003 and GN8811 tolerating high salinity and variable pH. Inoculation with GN8811 promoted maize growth comparable to nitrogen fertilization, and its genetically modified derivative (ΔnifL:PrpoD) showed further improvement even under high nitrogen conditions. These findings highlight the potential of combining microbial screening with genetic engineering to develop efficient bioinoculants for sustainable maize cultivation. Full article

This study aims to evaluate the antioxidant and anti-inflammatory potential of dichloromethanic, methanolic and hydroalcoholic extracts of seventeen different selected Balkan medicinal herbs with ethnopharmacological interest, with the goal of identifying the most bioactive candidates for further investigation of their therapeutic efficacy in human diseases. A total of fifty-four extracts were initially screened; due to the high sample number, only the most active samples were advanced to subsequent assays in order to identify bioactive candidates with potential therapeutic efficacy in human diseases. The methanolic extract of Cotinus coggygria showed the highest radical scavenging activity (DPPH: 96.4% inhibition), the hydroalcoholic extract of Hypericum empetrifolium exhibited the most potent iron chelation (IC₅₀: 5.0 μg/mL) and the methanolic extract of Sedum sediforme presented the best anti-inflammatory activity in in vitro assays (LOX IC₅₀: 39.4 μg/mL, COX-1 inhibition: 93.1% and COX-2 inhibition: 94.0%). Furthermore, significant inhibition of tyrosinase and collagenase was observed for the methanolic extract of Cistus creticus (94.2% tyrosinase inhibition, 86.8% collagenase inhibition) and the methanolic extract of Cotinus coggygria (83.1% tyrosinase inhibition, 96.1% collagenase inhibition). In vivo, five promising plant extracts were selected and evaluated for their anti-inflammatory activity using a carrageenan-induced paw edema model in female C57BL/6 mice. The study aimed to assess the in vivo anti-inflammatory potential of these extracts under acute inflammatory conditions. The methanolic extract of Cotinus coggygria proved the most active, significantly reducing paw edema by 34% compared to the non-treated control, indicating a pronounced anti-inflammatory effect and supporting its potential as a source of bioactive compounds with therapeutic relevance. The results of this study indicate that several selected herbal extracts exhibit notable pharmacological activities. Given their antioxidant, anti-inflammatory, and inhibitory properties against enzymes related to skin function, these extracts warrant further in vivo and (pre)clinical investigation for potential use in cosmetic and pharmaceutical products targeting skin disorders associated with inflammation and oxidative stress. Full article

Thalassemia is an inherited hemoglobin disorder characterized by chronic hemolytic anemia and substantial long-term healthcare needs. In β-thalassemia major, patients typically require regular red blood cell transfusions with iron chelation to prevent transfusional iron overload. Although supportive care has markedly improved survival, it is associated with a high treatment burden and does not provide a cure. In recent years, curative and disease-modifying therapies have expanded the treatment landscape. Allogeneic hematopoietic stem cell transplantation (HSCT) offers a potentially curative option for selected patients, while autologous gene therapy and gene-editing approaches have shown the capacity to achieve transfusion independence in clinical studies. In parallel, pharmacologic advances—including luspatercept, a transforming growth factor-beta (TGF-β) ligand trap—have been shown to enhance erythropoiesis and reduce transfusion requirements, and emerging agents such as fetal hemoglobin inducers (e.g., thalidomide) and the oral pyruvate kinase activator mitapivat have demonstrated clinically meaningful hemoglobin improvements in selected populations. Adjunctive strategies, including antioxidants, are under investigation to mitigate oxidative stress, and applications of artificial intelligence are increasingly used to support screening, diagnosis, and longitudinal monitoring of iron overload. This review synthesizes recent advances in curative therapies, novel pharmacologic agents, supportive strategies, and AI-enabled tools and highlights priorities for future clinical development and implementation. Full article

Phenolic-rich extracts from Satureja montana were evaluated before and after diazomethane treatment to determine how chemical derivatization influences their antioxidant capacity. Native and modified extracts were compared experimentally by measuring total phenolic content, ferric reducing antioxidant power (FRAP), and Fe²⁺-chelating ability. EN1 exhibited the highest concentration of phenolic compounds, reaching 1278.54 mmol/g, whereas EM2 retained only 1.99 mmol/g. In the FRAP assay, reducing power followed the order EN1 (9.36) > EN2 (3.72) > EM2 (2.08), with EM2 still exceeding caffeic, chlorogenic, and ferulic acids. In contrast, the modified extracts showed superior metal chelating capacity, with EM1 and EM2 displaying IC₅₀ values of 0.70 and 0.82 mg/mL, respectively, both markedly lower than those of the native extracts and the pure standards. To rationalize these differences, a DFT study was performed at the B3LYP/6-311++G(d,p) level, examining 18 proposed phenolic acids and their methylated derivatives associated with the extracts. All methylation reactions were thermodynamically favorable, particularly for compounds 18 (−57.10 kcal/mol), 16 (−53.96), 6 (−53.34), and 3, 9, and 11 (−52.71). Solvent effects were found to be structure-dependent: caffeic acid showed BDE values of 72.29, 73.59, and 74.43 kcal/mol in the gas phase, water, and benzene, respectively, whereas syringic acid displayed values of 80.44, 77.09, and 80.65 kcal/mol under the same conditions. Likewise, the ionization potential of caffeic acid decreased from 180.09 kcal/mol in the gas phase to 133.26 kcal/mol in water and 154.22 kcal/mol in benzene. Among all analyzed species, methyl 3,4-dihydroxycinnamate exhibited the lowest BDE (71.60 kcal/mol) as well as the most favorable ΔG°r toward HOO• (−11.06 kcal/mol). Full article

Given the established interplay between oxidative stress, cholinergic dysfunction, and metabolic imbalance in cognitive decline, this study investigated the multifunctional potential of three red macroalgae from the Madeira Archipelago (Asparagopsis taxiformis, Grateloupia lanceola, and Nemalion elminthoides) using a sequential biorefinery approach. Marine algae represent a sustainable source of functional food ingredients due to their rich content in bioactive compounds and their compatibility with low-impact production systems. Protein, ethanolic (phenolic-rich), and polysaccharide fractions were obtained through direct extraction and scalable biorefinery processing. Antioxidant activity was evaluated using ORAC, DPPH, FRAP, and FIC assays, while functionality relevant to human health was assessed through acetylcholinesterase, butyrylcholinesterase, and α-glucosidase inhibition. Protein extracts, particularly from N. elminthoides, exhibited strong hydrogen atom transfer-based antioxidant capacity, whereas ethanolic extracts demonstrated multifunctional activity, combining radical scavenging, metal chelation, and enzyme inhibition associated with neuroprotective and glycemic-regulation potential. Polysaccharide fractions contributed mainly to iron chelation and reducing capacity. Correlation analyses highlighted the complementary nature of antioxidant and bioactivity assays. Overall, these findings support the potential of Madeira red macroalgae as functional food ingredients and emphasize the importance of optimized biorefinery strategies to maximize nutritional and health-related benefits. Full article

Oxidative stress and inflammation are interconnected pathological processes involved in the progression of neurodegenerative, cardiovascular, and metabolic diseases, highlighting the need for multifunctional therapeutic agents targeting multiple pathways. In this study, two novel hybrid compounds were designed and synthesized in three steps by conjugating butylated phenolic moieties derived from butylated hydroxytoluene and p-coumaric acid with proline and γ-aminobutyric acid (GABA). The aim was the combination of antioxidant, anti-inflammatory, and cytoprotective properties within a single molecular framework. The compounds were evaluated using a comprehensive panel of in vitro and in vivo assays to assess antioxidant, metal-reducing, iron-chelating, antiglycation, anti-inflammatory, and acetylcholinesterase inhibitory activities. Both compounds exhibited significant antioxidant activity, with compound 2 demonstrating superior radical scavenging ability against DPPH, ABTS·⁺ and hydrogen peroxide (IC₅₀ 86 μM, 25 μM and 104 μM, respectively), enhanced ferric-reducing capacity (up to 91% of trolox activity), and strong iron-chelating activity (61.3%). Compound 2 also showed potent inhibition of lipid peroxidation (IC₅₀ 17.5 μM) and moderate antiglycation effects (44%), indicating substantial cytoprotective potential. Furthermore, both compounds selectively inhibited COX-2 over COX-1 and demonstrated moderate lipoxygenase inhibition, while compound 2 exhibited significant in vivo anti-inflammatory activity (53%), exceeding that of ibuprofen. Moderate acetylcholinesterase inhibition was also observed. In summary, the results confirm the design rationale, indicating that compound 2 could be further optimized as a multi-targeting molecule directed against oxidative stress- and inflammation-mediated conditions. Full article

Iron deficiency (ID) is frequent in patients with heart failure (HF) and is correlated with adverse outcomes, yet its involvement in HF pathophysiology is not fully understood. Hyperactivity of the sympathetic nervous system (SNS) is the central feature of HF. We aimed to compare the effects of isoproterenol (ISO), a β-adrenergic agonist (SNS stimulation), with those of the iron chelator deferoxamine (DEF), to evaluate how β-adrenergic stimulation influences cardiac iron. In this study, H9c2 cardiac cells were challenged with ISO, DEF or both and several parameters related to iron metabolism were analyzed. In all cases, the cells decreased their intracellular iron levels. ISO induced alterations in key cardiac iron metabolism molecules that were, in most cases, comparable to those elicited by DEF, emphasizing the direct impact of β-adrenergic stimuli on iron metabolism and mitochondrial dysfunction. Nevertheless, unlike DEF, ISO triggered a shift in mitochondrial energy metabolism. These findings suggest that β-adrenergic stimulation, as a major component of neurohormonal activation, may contribute to the development of ID in cardiac cells, highlighting the importance of iron homeostasis and the need to further investigate iron dysregulation in this context. Full article

Background/Objectives: Diabetic wound healing faces significant challenges due to the harsh microenvironment of wounds such as high blood glucose levels, excessive inflammation, persistent infection, upregulated reactive oxygen species (ROS), and damaged new blood vessels. Therefore, developing hydrogel dressings with microenvironmental regulation functions has become an important strategy in treating diabetic wounds. Methods: In this study, an ultraviolet in situ crosslinked hydrogel (D@H/E) was developed using methacrylic anhydride modified hyaluronic acid (HA-MA) and glycidyl methacrylate modified ε-polylysine (EPL-GMA), loaded with the iron chelating agent desferrioxamine (DFO). The physicochemical and biochemical properties of the hydrogel were comprehensively characterized, and its efficacy as a dressing for diabetic wounds was evaluated in a STZ-induced hyperglycemic mouse model. Results: This hydrogel demonstrated remarkable multidimensional effects by alleviating oxidative stress damage, inhibiting bacterial infection, regulating inflammatory responses, mitigating ferroptosis, and promoting cell migration and tubule formation. Specifically, the DFO-loaded hydrogel achieved a high DPPH radical scavenging efficiency of 80.8% and exhibited excellent antibacterial activity, with over 99.8% inhibition against both S. aureus and E. coli. In streptozotocin (STZ)-induced diabetic mice, the hydrogel accelerated wound closure to near completion by day 14. Mechanistically, it significantly upregulated CD206 expression to promote M2 macrophage polarization, upregulated the expression of angiogenesis-related factors to promote angiogenesis at the wound site, and enhanced GPX4 expression to alleviate ferroptosis. Conclusions: By orchestrating multi-dimensional synergy that combines ROS scavenging, infection control, immune regulation, and anti-ferroptosis, this D@H/E hydrogel system effectively remodels the harsh diabetic wound microenvironment, offering a promising platform for chronic wound management. Full article

Introduction: Hereditary hemochromatosis is a genetic disorder characterized by dysregulation of iron homeostasis, resulting in excessive intestinal iron absorption and progressive iron deposition in vital organs. The hepcidin–ferroportin axis plays a central role in the pathophysiology of the disease, particularly in cases associated with mutations in the HFE gene. Persistent iron overload may lead to progressive injury in target organs and functional impairment. Methods: A brief description of the pathological basis of hereditary hemochromatosis was conducted together with a systematic review of interventional clinical trials registered on ClinicalTrials.gov. Studies with available results were included regardless of clinical phase or recruitment status. Relevant data regarding therapeutic interventions and iron metabolism parameters were extracted and descriptively analyzed. Results: Three studies met the inclusion criteria: one evaluating the hepcidin mimetic Rusfertide (PTG-300), another assessing synthetic hepcidin LJPC-401, and a third investigating the iron chelator Deferasirox. Discussion: These therapies demonstrated biological activity in modulating iron metabolism parameters; however, none proved superior to therapeutic phlebotomy, which remains the standard treatment, in terms of efficacy. Conclusions: Although emerging pharmacological therapies targeting iron metabolism show promising biological effects, current clinical evidence remains limited. Therapeutic phlebotomy continues to represent the first-line treatment for hereditary hemochromatosis, and further clinical trials are necessary to determine the potential role of these novel therapeutic approaches. Full article

Chelating agents can extend the operational pH range of iron-based advanced oxidation processes, yet comprehensive studies on chelated Fe-activated persulfate systems for textile dye degradation remain scarce. This study establishes an integrated framework for optimizing Fe(II)/persulfate (PS) systems using chelating ligands and hybrid energy inputs under near-neutral conditions. Among the tested systems, Fe(II)/PS complexed with citric acid (CA) exhibited superior performance, achieving ~91% dye removal within 20 min at pH 6.5 under optimized conditions (1.25 mM Fe(II), 10 mM PS, 0.1 mM CA). Chelation stabilized Fe redox cycling and prevented precipitation, enabling effective catalysis across pH 3–10. Optimal CA/Fe and Fe/PS ratios (0.1:1.25 and 1.25:10) yielded ~96% decolorization and 67.65% TOC removal in 60 min, while excessive chelation reduced activity. Transition metal screening (Mn(II), Zn(II), Cu(II), Co(II), and Ni(II) confirmed Fe(II) as the most effective activator, providing removal efficiencies up to 3.2-fold higher than competing metals. Mixed-dye experiments showed competitive degradation, with >37% color removal after 60 min for ternary dye mixtures. Mineralization reached ~92% TOC reduction after 120 min, indicating deep oxidation beyond chromophore cleavage. Reactive species quenching revealed a mixed oxidation mechanism involving ^•OH radicals and high-valent Fe(IV) species. Hybrid assistance improved mineralization, with UVC increasing TOC removal by 15.6%, while solar irradiation provided moderate enhancement under low-energy input. In contrast, low-power ultrasound (40 kHz, 60 W) delivered only 17.6 W acoustic power to the solution and did not improve performance due to limited cavitation and mixing. This work thus contributes a robust platform for advancing chelated iron-persulfate oxidation systems toward practical, effective treatment of recalcitrant dye-contaminated wastewaters under near-neutral conditions. Full article

Uveal melanoma (UM) represents an uncommon intraocular malignancy with high aggressiveness. Dysregulation of ferroptosis has been associated with UM progression. Dihydroartemisinin (DHA), a natural derivative of Artemisia annua, exhibits potent antitumor activity with a favorable safety profile, yet its role in ferroptosis regulation in UM remains unclear. Here, we showed that DHA significantly reduced the proliferation and invasiveness of UM cells—both primary and secondary—with effects intensifying over time and dose. Transcriptomic analysis indicated that DHA may exert antitumor effects by modulating the ferroptosis-related pathway, characterized by upregulating heme oxygenase-1 (HO-1) and downregulating the SLC7A11 (xCT)/GPX4 axis, leading to iron accumulation, increased ROS and lipid peroxidation, and mitochondrial dysfunction. Iron chelators and pancaspase inhibitors partially reverse these effects, whereas HO-1 inducers enhance them. Overall, our results suggest that DHA suppresses UM progression by inducing ferroptosis and mitochondrial dysfunction, while the HO-1 and xCT/GPX4 pathways may contribute to these effects. DHA may represent a potential therapeutic approach for UM, warranting further investigation. Full article

Recent phytochemical investigations have demonstrated that Luvunga scandens is a rich source of structurally diverse secondary metabolites; however, its potential antioxidant-active constituents and their underlying mechanisms remain largely unexplored. In this study, an NMR-guided fractionation strategy applied to the rhizomes and leaves of L. scandens led to the isolation of ten limonoids, including three new compounds, Luvungas B–D (3, 4, and 8). Their structures and absolute configurations were determined through extensive spectroscopic analysis, X-ray diffraction, and ECD calculations. Based on the isolated analogues, a biosynthetic pathway is proposed, featuring the metabolic bifurcation of a key acyclic intermediate into the isoobacunoic acid and propellane-type lineages. Biological evaluation revealed that 8 inhibits RSL3-induced ferroptosis in HepaRG liver cells with an EC₅₀ of 16.1 µM. Mechanistic studies demonstrated that, unlike classical antioxidants, compound 8 mitigates lipid peroxidation without exhibiting direct radical-scavenging or iron-chelating activities. These findings suggest that 8 suppresses ferroptosis via non-canonical mechanisms. Full article

Carnosine (or β-alanyl-L-histidine) is an endogenous compound playing very important roles in human organisms as antiglycation and antioxidant agents, and, in addition, helping to mitigate illnesses such as cancer and neurodegenerative diseases. Aiming to explore the chelating ability of carnosine, based on its coordinating possibilities, we started to investigate the metal complexes of essential copper(II), zinc(II), and iron(II) ions coordinated to this dipeptide. Different compounds were isolated in the solid state by adding stoichiometric amounts of metal salts to carnosine at controlled pH or under a controlled atmosphere, with the formation of mono-, bi- and polynuclear species. These complexes were subsequently characterized mainly by spectroscopic techniques (UV–Vis, IR, EPR), in addition to elemental analysis. A binuclear species was isolated with copper(II) and had its structure determined by X-ray diffraction, improving previously reported data in the literature. Two insoluble correlated trinuclear species were isolated with zinc(II) ions, using perchlorate or chloride as counter-ions. In the case of iron, a mononuclear species was verified with Fe(II) ions, obtained under an inert atmosphere. Further, the antioxidant properties of free carnosine and the copper–carnosine complex were verified by their scavenging activity toward the ABTS^•+ radical, using Trolox as a reference, showing significant activity. The carnosine–metal complexes were also tested as potential antineoplastic agents, in comparison to the free ligand, after 24 h of incubation at 37 °C, using malignant HeLa, SKMEL 28 and SKMEL 147, and non-tumor fibroblast cells. Results indicated neglected or poor anti-proliferative properties of these metal complexes, when compared to other similar compounds described in the literature. Full article