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26 pages, 1295 KB  
Article
Adaptation and Bioremediation Efficiency of UV-Mutagenized Microalgae in Undiluted Agro-Industrial Effluents from Mexico
by Cesar E. Najar-Almanzor, Rosa Leonor González-Díaz, Tomás García-Cayuela and Danay Carrillo-Nieves
Environments 2025, 12(9), 307; https://doi.org/10.3390/environments12090307 (registering DOI) - 31 Aug 2025
Abstract
Microalgae offer a sustainable alternative for wastewater treatment by simultaneously removing pollutants and producing biomass of potential value. This study evaluated five species—Haematococcus pluvialis, Chlorella vulgaris, Chlamydomonas sp., Anabaena variabilis, and Scenedesmus sp.—in three undiluted food and beverage industry [...] Read more.
Microalgae offer a sustainable alternative for wastewater treatment by simultaneously removing pollutants and producing biomass of potential value. This study evaluated five species—Haematococcus pluvialis, Chlorella vulgaris, Chlamydomonas sp., Anabaena variabilis, and Scenedesmus sp.—in three undiluted food and beverage industry effluents from Mexico: nejayote (alkaline wastewater generated during corn nixtamalization for tortilla production), tequila vinasses (from tequila distillation), and cheese whey (from cheese making). Strains were adapted through UV mutagenesis and gradual acclimatization to grow without freshwater dilution. Bioremediation efficiency was assessed via reductions in chemical oxygen demand (COD), total nitrogen (TN), and total phosphates (TPO4). C. vulgaris achieved complete TN and TPO4 removal and 90.2% COD reduction in nejayote, while A. variabilis reached 81.7% COD and 79.3% TPO4 removal in tequila vinasses. In cheese whey, C. vulgaris removed 55.5% COD, 53.0% TN, and 35.3% TPO4. These results demonstrate the feasibility of microalgae-based systems for treating complex agro-industrial wastewaters, contributing to sustainable and circular wastewater management. Full article
(This article belongs to the Special Issue Environments: 10 Years of Science Together)
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18 pages, 371 KB  
Review
Nephroprotective Mechanisms of SGLT2i: Beyond the Glucose-Lowering Effect
by Alessio Mazzieri and Livia Maria Rita Marcon
Biomedicines 2025, 13(9), 2123; https://doi.org/10.3390/biomedicines13092123 (registering DOI) - 30 Aug 2025
Abstract
Chronic kidney disease (CKD) is a fast-growing cause of death worldwide. Systemic hypertension and diabetes mellitus are the major causes of kidney damage leading to a reduction in glomerular filtration rate and to urinary protein loss. Sodium–glucose cotransporter 2 inhibitors (SGLT2is) are drugs [...] Read more.
Chronic kidney disease (CKD) is a fast-growing cause of death worldwide. Systemic hypertension and diabetes mellitus are the major causes of kidney damage leading to a reduction in glomerular filtration rate and to urinary protein loss. Sodium–glucose cotransporter 2 inhibitors (SGLT2is) are drugs able to address both of these deleterious effects, preventing kidney damage from progressing. Initially born as hypoglycemic agents, SGLT2is subsequently proved to have not only positive metabolic but also pleiotropic effects on the kidney and the cardiovascular system. Indeed, they improve the metabolic profile, reducing uric acid, blood sugar levels, and body weight. Moreover, they exert an anti-inflammatory and antifibrotic effect, reducing endothelial dysfunction and reactive oxygen species (ROS) production. Finally, they reduce renal hyperfiltration and control blood pressure, inducing osmotic diuresis and restoring tubulo-glomerular feedback. All these metabolic, anti-inflammatory, and hemodynamic effects contribute to significantly reducing the risk of cardiorenal events, as widely demonstrated in randomized clinical trials. The pleiotropic actions of SGLT2is together with their good tolerability make them a pillar treatment of CKD regardless of the presence of diabetes mellitus. Further studies will be needed in order to expand the indications to populations previously excluded from clinical trials such as transplant recipients or glomerulonephritis patients. This narrative review aims to summarize current knowledge regarding the nephroprotective mechanisms of SGLT2is which, after initial use as a hypoglycemic agent, have assumed a pivotal role in the actual and future management of patients with CKD. Full article
16 pages, 2218 KB  
Article
Transgenerational and Molecular Responses to Lanthanum Exposure in a Spodoptera littoralis-Brassica rapa System
by Cong van Doan, Sara Bonzano and Massimo E. Maffei
Int. J. Mol. Sci. 2025, 26(17), 8462; https://doi.org/10.3390/ijms26178462 (registering DOI) - 30 Aug 2025
Abstract
The widespread use of rare earth elements (REEs) in agriculture, particularly Lanthanum (La), raises concerns about their ecological impact on non-target organisms. We investigated the direct and indirect effects of La on the insect pest Spodoptera littoralis and its host plant, Brassica rapa [...] Read more.
The widespread use of rare earth elements (REEs) in agriculture, particularly Lanthanum (La), raises concerns about their ecological impact on non-target organisms. We investigated the direct and indirect effects of La on the insect pest Spodoptera littoralis and its host plant, Brassica rapa. Direct exposure to La-supplemented diets reduced larval growth, survival, and egg production. Interestingly, a transgenerational effect was observed, where larvae from La-exposed parents exhibited increased resilience, showing no performance reduction on the same diets. Indirectly, La accumulation in plants mediated a hormetic response in herbivores, increasing larval weight at low concentrations but reducing it at high concentrations, while modulating their oxidative stress and detoxification gene expression. From the plant perspective, La exposure amplified herbivory-induced calcium signalling and altered the expression of key genes related to calcium and reactive oxygen species pathways. These findings reveal the complex ecological risks of La accumulation in agroecosystems, affecting both plants and insects directly and through novel transgenerational effects. Full article
(This article belongs to the Special Issue New Insights into Plant and Insect Interactions (Second Edition))
15 pages, 2017 KB  
Article
Antioxidant Effects of Carnosine-Enriched Chicken Meat Consumption in Athletes: Modulation of SOD Activity and Superoxide Levels—A Randomized Control Trial
by Nikolina Kolobarić, Leon Perić, Zrinka Mihaljević, Petar Šušnjara, Alina Boris, Ines Drenjančević, Ivana Jukić and Ana Stupin
Antioxidants 2025, 14(9), 1069; https://doi.org/10.3390/antiox14091069 (registering DOI) - 30 Aug 2025
Abstract
Dipeptide carnosine has gained attention for its antioxidant and anti-inflammatory effects demonstrated in preclinical studies, but evidence from human trials remains limited. This study investigated whether dietary carnosine delivered through enriched chicken meat can modulate redox status in competitive athletes. This randomized controlled [...] Read more.
Dipeptide carnosine has gained attention for its antioxidant and anti-inflammatory effects demonstrated in preclinical studies, but evidence from human trials remains limited. This study investigated whether dietary carnosine delivered through enriched chicken meat can modulate redox status in competitive athletes. This randomized controlled trial involved 35 male competitive athletes who were assigned to either a control group (N = 16; CTRL) consuming regular chicken meat (410 mg/day) or a carnosine group (N = 19; CAR) receiving carnosine-enriched chicken meat (590 mg/day) for 21 days. Blood sample collection, cells isolation and anthropometric measurements were performed before and after the intervention to assess antioxidant enzyme activity, intracellular reactive oxygen species production, 8-iso Prostaglandin F2α (8-iso PGF 2α) concentration, and cell adhesion molecules serum concentrations. Results were expressed as mean ± standard deviation (SD). Group comparisons were conducted using parametric and non-parametric tests, ANCOVA was applied to assess post-intervention differences adjusted for baseline values, while a two-way ANOVA was performed to determine the significance of interactions between time and treatment for each parameter, significance set at p < 0.05. CAR group showed a significant reduction in serum 8-iso PGF 2α and increased SOD activity compared to baseline and the CTRL group. Intracellular hydrogen peroxide and peroxynitrite production increased, while superoxide anion production decreased in the CAR group. Carnosine-enriched chicken meat consumption significantly reduced lipid peroxidation, increased serum enzyme activity, and decreased superoxide anion production in competitive athletes. While further research is needed to elucidate the mechanisms and key factors behind it, the observed changes indicate that carnosine-enriched chicken meat consumption affects SOD activity consequently producing an antioxidative effect. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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34 pages, 1250 KB  
Review
Next-Gen Neuroprotection in Glaucoma: Synergistic Molecules for Targeted Therapy
by Alessio Martucci, Massimo Cesareo, Maria Dolores Pinazo-Durán, Francesco Aiello, Giulio Pocobelli, Raffaele Mancino and Carlo Nucci
J. Clin. Med. 2025, 14(17), 6145; https://doi.org/10.3390/jcm14176145 (registering DOI) - 30 Aug 2025
Abstract
Background: Glaucoma is a progressive optic neuropathy marked by retinal ganglion cells (RGCs), apoptosis, vascular insufficiency, oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. While intraocular pressure (IOP) reduction remains the primary intervention, many patients continue to lose vision despite adequate pressure control. Emerging [...] Read more.
Background: Glaucoma is a progressive optic neuropathy marked by retinal ganglion cells (RGCs), apoptosis, vascular insufficiency, oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. While intraocular pressure (IOP) reduction remains the primary intervention, many patients continue to lose vision despite adequate pressure control. Emerging neuroprotective agents—citicoline, coenzyme Q10 (CoQ10), pyruvate, nicotinamide, pyrroloquinoline quinone (PQQ), homotaurine, berberine, and gamma-aminobutyric acid (GABA)—target complementary pathogenic pathways in experimental and clinical settings. Methods: This literature review synthesizes current evidence on glaucoma neuroprotection, specifically drawing on the most relevant and recent studies identified via PubMed. Results: Citicoline enhances phospholipid synthesis, stabilizes mitochondrial membranes, modulates neurotransmitters, and improves electrophysiological and visual field outcomes. CoQ10 preserves mitochondrial bioenergetics, scavenges reactive oxygen species, and mitigates glutamate-induced excitotoxicity. Pyruvate supports energy metabolism, scavenges reactive oxygen species, and restores metabolic transporter expression. Nicotinamide and its precursor nicotinamide riboside boost NAD+ levels, protect against early mitochondrial dysfunction, and enhance photopic negative response amplitudes. PQQ reduces systemic inflammation and enhances mitochondrial metabolites, while homotaurine modulates GABAergic signaling and inhibits β-amyloid aggregation. Berberine attenuates excitotoxicity, inflammation, and apoptosis via the P2X7 and GABA-PKC-α pathways. Preclinical models demonstrate synergy when agents are combined to address multiple targets. Clinical trials of fixed-dose combinations—such as citicoline + CoQ10 ± vitamin B3, citicoline + homotaurine ± vitamin E or PQQ, and nicotinamide + pyruvate—show additive improvements in RGCs’ electrophysiology, visual function, contrast sensitivity, and quality of life without altering IOP. Conclusions: A multi-targeted approach is suitable for glaucoma’s complex neurobiology and may slow progression more effectively than monotherapies. Ongoing randomized controlled trials are essential to establish optimal compound ratios, dosages, long-term safety, and structural outcomes. However, current evidence remains limited by small sample sizes, heterogeneous study designs, and a lack of long-term real-world data. Integrating combination neuroprotection into standard care holds promise for preserving vision and reducing the global burden of irreversible glaucoma-related blindness. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Glaucoma)
23 pages, 7398 KB  
Article
Heterogeneous Photocatalytic Degradation of a Glucocorticoid in Aqueous Solution and Industrial Wastewater Using TiO2-Zn(II)-Clinoptilolite Catalyst
by Andrea G. Briseño-Peña, Monserrat Castañeda-Juárez, Verónica Martínez-Miranda, Ivonne Linares-Hernández, Fortunata Santoyo-Tepole, Marcos Solache-Ríos, Elia Alejandra Teutli-Sequeira, Carlos R. Fonseca and Mario Esparza-Soto
Processes 2025, 13(9), 2781; https://doi.org/10.3390/pr13092781 - 29 Aug 2025
Abstract
Dexamethasone (DXM) is a glucocorticoid widely used in treating various diseases, but its extensive use raises environmental concerns due to poor absorption and rapid excretion, leading to its presence in aquatic environments. In this study, aqueous DXM was treated via heterogeneous solar photocatalysis [...] Read more.
Dexamethasone (DXM) is a glucocorticoid widely used in treating various diseases, but its extensive use raises environmental concerns due to poor absorption and rapid excretion, leading to its presence in aquatic environments. In this study, aqueous DXM was treated via heterogeneous solar photocatalysis (HSP) using a Zn-doped TiO2 catalyst supported on zeolite clinoptilolite (TiO2-Zn(II)-ZC), synthesized by electrodeposition. The catalyst was characterized by IR spectroscopy, SEM-EDS, XRD, atomic absorption spectroscopy, and Pzc determination. A Box–Behnken design was applied to evaluate the influence of initial DXM concentration (5–15 mg/L), hydraulic retention time (HRT: 30–60 min), and catalyst dose (0.5–1.5 g/L), using DXM (UV–Vis) and COD as response variables. Optimal conditions (12.5 mg/L DXM, 60 min HRT, 1.0 g/L catalyst) achieved 80% DXM removal (UV–Vis), 88.71% (HPLC), 85.29% COD removal, and 82.86% TOC reduction at 67 °C, 325.12 kJ/L, and 38.77 W/m2. Additionally, a treated sample of chocolate industry wastewater enriched with 12.5 mg/L DXM (DXM-WW) achieved 67.88% (HPLC), 93.02% (COD), and 92.38% (TOC) removal. The catalyst reduced the bandgap, enabling sunlight-driven generation of e/h+ pairs and reactive oxygen species (OH, H2O2, and O2•−), facilitating DXM degradation. Full article
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17 pages, 855 KB  
Article
Ozone Nanobubble Water as a Sustainable Strategy to Enhance Metabolism, Muscle Function, and Exercise Performance in Mice
by Cheng-Jeng Tsai, Peng-Cheng Hsu, Meng-l Kuo and Yi-Ming Chen
Nutrients 2025, 17(17), 2821; https://doi.org/10.3390/nu17172821 - 29 Aug 2025
Abstract
Background/Objectives: Nanobubble water (NBW) is being studied increasingly for its potential benefits in sports nutrition. This study aimed to evaluate whether supplementation with ozone-enriched NBW (O3-NBW) could improve integrated exercise capacity—encompassing endurance performance, muscle strength, and postexercise recovery as well [...] Read more.
Background/Objectives: Nanobubble water (NBW) is being studied increasingly for its potential benefits in sports nutrition. This study aimed to evaluate whether supplementation with ozone-enriched NBW (O3-NBW) could improve integrated exercise capacity—encompassing endurance performance, muscle strength, and postexercise recovery as well as body composition and metabolic adaptations in mice. Methods: Male ICR mice (n = 24) were allocated into Control, Air-NBW, or O3-NBW (0.2–1 mg/L ozone) groups for 4 weeks. Results: O3-NBW treatment considerably enhanced forelimb grip strength and treadmill running endurance compared to the Control group (both p < 0.05). Analyses of body composition revealed a higher proportion of lean mass and muscle glycogen storage in NBW groups, notably with O3-NBW. Serum markers gathered post-exercise demonstrated a reduction in ammonia and blood urea nitrogen (BUN), suggesting improved nitrogen metabolism. Levels of resting serum creatine kinase (CK) and uric acid were also lower in O3-NBW mice, indicating potential benefits for muscle recovery. In addition, O3-NBW treatment significantly enhanced oxygen consumption (VO2) and reduced the respiratory quotient (RQ), signifying amplified fat oxidation, while also lowering total energy expenditure (all p < 0.05). Spontaneous wheel-running activity remained consistent across all the groups. Conclusions: Taken as a whole, these findings emphasize that O3-NBW supplementation offers ergogenic and metabolic advantages by improving integrated exercise capacity and efficiency of gas exchange, without adverse effects. Full article
20 pages, 6101 KB  
Article
Inhibitory Effects of Artemisia argyi Extracts on Microcystis aeruginosa: Anti-Algal Mechanisms and Main Allelochemicals
by Jiajia Dong, Peng Li, Yalei Du, Lingling Cao and Zhiqiang Yan
Biology 2025, 14(9), 1141; https://doi.org/10.3390/biology14091141 - 29 Aug 2025
Abstract
Harmful cyanobacterial blooms (CyanoHABs) threaten freshwater ecosystems and human health. Inhibiting cyanobacteria through plant allelopathy is an effective and environmentally friendly approach for CyanoHAB control. In this study, we evaluated the inhibitory activities of several organic solvent extracts from Artemisia argyi against the [...] Read more.
Harmful cyanobacterial blooms (CyanoHABs) threaten freshwater ecosystems and human health. Inhibiting cyanobacteria through plant allelopathy is an effective and environmentally friendly approach for CyanoHAB control. In this study, we evaluated the inhibitory activities of several organic solvent extracts from Artemisia argyi against the common bloom-forming cyanobacterium Microcystis aeruginosa, explored the anti-algal mechanism of the active fraction, analyzed its secondary metabolites using liquid chromatography–high-resolution mass spectrometry (LC-HRMS), and screened the potential allelochemicals. The results showed that the crude extract of A. argyi leaves (CE) exhibited significant inhibitory effects on M. aeruginosa. Among several solvent fractions of CE, the dichloromethane extract (DE) demonstrated the strongest inhibitory effect, with a 7-day IC50 of 70.43 mg/L. After treatment with DE, the contents of chlorophyll a (Chl a), carotenoids, and phycobiliproteins (PBPs) in M. aeruginosa were significantly reduced. Meanwhile, an excessive accumulation of reactive oxygen species (ROS), reduction of catalase (CAT) activity, increase in malondialdehyde (MDA) content, and shrinkage of the membrane were found in M. aeruginosa cells under DE treatments. There were 81 secondary metabolites annotated in DE by LC-HRMS. Among them, hispidulin, jaceosidin, 5,7,3′-trihydroxy-6,4′,5′-trimethoxyflavone, and eupatilin possessed strong inhibitory activities, with 7-day IC50 values of 26.23, 27.62, 32.02, and 34.98 mg/L, respectively. These results indicated that the A. argyi extracts possess significant allelopathic activities on M. aeruginosa, and DE was identified as the primary active fraction. It inhibits algae growth by suppressing photosynthesis and inducing peroxidation, ultimately leading to cell death. Flavonoids in DE were the main allelochemicals responsible for the inhibition on algae of A. argyi extracts. Full article
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23 pages, 1749 KB  
Review
ZnO-Based Nanoparticles for Targeted Cancer Chemotherapy and the Role of Tumor Microenvironment: A Systematic Review
by Vasilis-Spyridon Tseriotis, Dimitrios Ampazis, Sofia Karachrysafi, Theodora Papamitsou, Georgios Petrakis, Dimitrios Kouvelas, Paraskevas Mavropoulos, Konstantinos Lallas, Aleksandar Sič, Vasileios Fouskas, Konstantinos Stergiou, Pavlos Pavlidis and Marianthi Arnaoutoglou
Int. J. Mol. Sci. 2025, 26(17), 8417; https://doi.org/10.3390/ijms26178417 - 29 Aug 2025
Abstract
Cancer, a leading global cause of death responsible for nearly 10 million deaths annually, demands innovative therapeutic strategies. Intrinsic cytotoxicity and biocompatibility of zinc oxide nanoparticles (ZnO-NPs) have rendered them promising nanoplatforms in oncology. We herein systematically review their applications for targeted cancer [...] Read more.
Cancer, a leading global cause of death responsible for nearly 10 million deaths annually, demands innovative therapeutic strategies. Intrinsic cytotoxicity and biocompatibility of zinc oxide nanoparticles (ZnO-NPs) have rendered them promising nanoplatforms in oncology. We herein systematically review their applications for targeted cancer chemotherapy, with a focus on physicochemical properties, drug delivery mechanisms, and interactions with the tumor microenvironment (TME). We searched PubMed, SCOPUS, and Web of Science from inception through December 2024 for peer-reviewed preclinical studies on cancer models. Results were qualitatively synthesized. Quality was assessed with the SYRCLE risk of bias tool. Among 20 eligible studies, ZnO-NPs were frequently functionalized with ligands to enhance tumor targeting and minimize systemic toxicity. Chemotherapeutic agents (doxorubicin, 5-fluorouracil, docetaxel, cisplatin, gemcitabine, and tirapazamine) were loaded into ZnO-based carriers, with improved anticancer efficacy compared to free drug formulations, particularly in multidrug-resistant cell lines and in vivo murine xenografts. The mildly acidic TME was exploited for pH-responsive drug release, premature leakage reduction, and improvement of intratumoral accumulation. Enhanced therapeutic outcomes were attributed to reactive oxygen species generation, zinc ion-mediated cytotoxicity, mitochondrial dysfunction, and efflux pump inhibition. Deep tumor penetration, apoptosis induction, and tumor growth suppression were also reported, with minimal toxicity to healthy tissues. ZnO-NPs might constitute a versatile and promising strategy for targeted cancer chemotherapy, offering synergistic anticancer effects and improved safety profiles. Future studies emphasizing long-term toxicity, immune responses, and scalable production could lead to clinical translation of ZnO-based nanomedicine in oncology. Full article
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22 pages, 1862 KB  
Article
Effects of Dietary and Probiotic Interventions in Patients with Metabolic Syndrome and Obstructive Sleep Apnea
by Amina Venter, Amin-Florin El-kharoubi, Mousa El-kharoubi, Evelin Claudia Ghitea, Marc Cristian Ghitea, Timea Claudia Ghitea and Ciprian Florian Venter
Clin. Pract. 2025, 15(9), 159; https://doi.org/10.3390/clinpract15090159 - 29 Aug 2025
Abstract
Background: Metabolic syndrome (MS) and obstructive sleep apnea (OSA) frequently coexist, exacerbating systemic inflammation, oxidative stress, and metabolic dysregulation. This study evaluates the effects of dietary and probiotic interventions, compared to a non-intervention control group, on metabolic, hemodynamic, and neurochemical parameters, with a [...] Read more.
Background: Metabolic syndrome (MS) and obstructive sleep apnea (OSA) frequently coexist, exacerbating systemic inflammation, oxidative stress, and metabolic dysregulation. This study evaluates the effects of dietary and probiotic interventions, compared to a non-intervention control group, on metabolic, hemodynamic, and neurochemical parameters, with a specific focus on the neurotransmitters GABA and glutamate. Methods: In a prospective randomized study (2020–2023), 120 patients with coexisting MS and OSA were assigned to three groups: control (n = 36), diet therapy (n = 42), and diet therapy combined with probiotics (n = 42). Interventions lasted six months and included personalized dietary plans and probiotic supplementation. Outcome measures included BMI, visceral fat, HOMA index, lipid profile, oxygen saturation, and urinary GABA and glutamate levels. Unsupervised K-means clustering and principal component analysis (PCA) were applied to identify phenotypic response patterns based on delta values. Results: Diet therapy led to significant reductions in BMI (−15.7%, p = 0.001), visceral fat (−17.3%, p = 0.001), triglycerides (−14.6%, p = 0.003), uric acid (−9.5%, p = 0.011), and C-reactive protein (CRP) (−21.4%, p = 0.007). The combined intervention group exhibited further improvements in visceral fat (−22.8%, p = 0.001), glutamate (−18.2%, p = 0.002), and GABA levels (+19.5%, p = 0.001). Oxygen saturation improved across all groups, with the greatest increase in the probiotics group (+2.3%). Clustering analysis revealed three distinct response phenotypes—strong, moderate, and non-responders—highlighting inter-individual variability in treatment efficacy. Conclusions: Personalized dietary interventions, especially when paired with probiotics, effectively improve metabolic, inflammatory, and neurochemical profiles in patients with MS and OSA. Integrating clustering algorithms enables phenotype-specific stratification, offering a step toward precision lifestyle medicine. Future studies should explore long-term outcomes and refine microbiota-targeted approaches to optimize intervention efficacy. Full article
(This article belongs to the Special Issue The Effect of Dietary Compounds on Inflammation-Mediated Diseases)
22 pages, 2419 KB  
Review
Mitochondrial Reverse Electron Transport: Mechanisms, Pathophysiological Roles, and Therapeutic Potential
by Yanyu Bao, Cuilan Hu, Bing Wang, Xiongxiong Liu, Qingfeng Wu, Dan Xu, Zheng Shi and Chao Sun
Biology 2025, 14(9), 1140; https://doi.org/10.3390/biology14091140 - 29 Aug 2025
Abstract
Mitochondrial reverse electron transport (RET) represents a fundamental but potentially hazardous metabolic process in eukaryotic cells. This review systematically examines current understanding of RET mechanisms and their pathophysiological consequences. RET occurs when electrons flow inversely from reduced coenzyme Q (CoQH2) to [...] Read more.
Mitochondrial reverse electron transport (RET) represents a fundamental but potentially hazardous metabolic process in eukaryotic cells. This review systematically examines current understanding of RET mechanisms and their pathophysiological consequences. RET occurs when electrons flow inversely from reduced coenzyme Q (CoQH2) to complex I, driven by excessive reduction of the CoQ pool and elevated mitochondrial membrane potential, resulting in substantial superoxide production. While moderate RET contributes to physiological redox signaling, sustained RET activation leads to oxidative damage and activates regulated cell death pathways. Notably, RET demonstrates metabolic duality: it facilitates ATP generation through NAD+ reduction while simultaneously inducing mitochondrial dysfunction via reactive oxygen species overproduction. Pathologically, RET has been implicated in myocardial ischemia–reperfusion injury, neurodegenerative disorders including Alzheimer’s diseases, and exhibits context-dependent roles in tumor progression. Emerging evidence also suggests RET involvement in microbial pathogenesis through modulation of host immune responses. These findings position RET as a critical regulatory node in cellular metabolism with broad implications for human diseases. Future investigations should focus on developing tissue-specific RET modulators and elucidating the molecular switches governing its activation threshold, which may yield novel therapeutic strategies for diverse pathological conditions. Full article
(This article belongs to the Special Issue Mitochondria and Cardiovascular Diseases)
16 pages, 2947 KB  
Article
1,10-Phenanthroline-Iron Complex-Derived Fe-N-C Electrocatalysts: Enhanced Oxygen Reduction Activity and Stability Through Synthesis Tuning
by Carlos S. A. Vasconcellos, Nelson A. Galiote, Nadeem Khan, Enrique A. Paredes-Salazar, Maykon L. Souza, Kotaro Sasaki, Meng Li and Fabio H. B. Lima
Catalysts 2025, 15(9), 821; https://doi.org/10.3390/catal15090821 - 29 Aug 2025
Viewed by 47
Abstract
The development of electrocatalysts composed of earth-abundant elements is essential for advancing the commercial application of Proton Exchange Membrane Fuel Cells (PEMFC). Among these, single-atom electrocatalysts, such as Fe-N-C, show great promise for the oxygen reduction reaction (ORR). This study aims to improve [...] Read more.
The development of electrocatalysts composed of earth-abundant elements is essential for advancing the commercial application of Proton Exchange Membrane Fuel Cells (PEMFC). Among these, single-atom electrocatalysts, such as Fe-N-C, show great promise for the oxygen reduction reaction (ORR). This study aims to improve the ORR activity and stability of Fe-N-C electrocatalysts by fine-tuning the straightforward 1,10-phenanthroline-iron complexation synthesis method. Key parameters, including iron-to-phenanthroline ratio, carbon powder surface area, and pyrolysis temperature were systematically varied to evaluate their influence on the resulting electrocatalysts. The findings of this study revealed that the electrocatalysts synthesized with 1,10-phenanthroline (Phen) and high-surface-area Black Pearls (BP) possessed much better ORR activity than electrocatalysts prepared by using Vulcan carbon (lower surface area). Interestingly, electrocatalysts prepared with BP, but with a non-bidentate nitrogen-containing ligand molecule, such as imidazole, showed a much poorer activity, as the resulting material predominantly consisted of inactive structures, such as encapsulated iron nanoparticles and iron oxide, as evidenced by HR-TEM, EXAFS, and XRD. Therefore, the results suggest that only the synergistic combination of the bidentate ligand phenanthroline (Phen) and the high-surface-area carbon support (BP) favored the formation of ORR-active Fe-N-C single-atom species upon pyrolysis. The study also unveiled a significant enhancement in electrocatalyst stability during accelerated durability tests (and air storage) as the pyrolysis temperature was increased from 700 to 1300 °C, albeit at the expense of ORR activity, likely resulting from the generation of iron particles. Pyrolysis at 1050 °C yielded the electrocatalyst with the most favorable balance of activity and stability in rotating disk measurements, while maintaining moderate durability under PEM fuel cell operation. The insights obtained in this study may guide the development of more active efficient and durable electrocatalysts, synthesized via a simple method using earth-abundant elements, for application in PEMFC cathodes. Full article
(This article belongs to the Section Electrocatalysis)
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16 pages, 2535 KB  
Article
Effect of the Microstructure of Carbon Supports on the Oxygen Reduction Properties of the Loaded Non-Noble Metal Catalysts
by Dan Ma, Yudong Zhang, Menghan Liang, Runyu Niu, Yao Ge, Yanan Zou and Xiaorui Dong
Nanomaterials 2025, 15(17), 1327; https://doi.org/10.3390/nano15171327 - 29 Aug 2025
Viewed by 94
Abstract
The development of efficient non-noble metal catalysts is critical for advancing sustainable fuel-cell technologies. This study investigates the effect of carbon support microstructure on the oxygen reduction reaction (ORR) performance of Fe-N-C catalysts. By precisely tuning the pyrolysis temperature of activated carbon (AC) [...] Read more.
The development of efficient non-noble metal catalysts is critical for advancing sustainable fuel-cell technologies. This study investigates the effect of carbon support microstructure on the oxygen reduction reaction (ORR) performance of Fe-N-C catalysts. By precisely tuning the pyrolysis temperature of activated carbon (AC) between 600 and 1000 °C, we elucidate the mechanistic influence of the physicochemical characteristics of the carbon support on the ORR activity of the supported catalyst. Increasing the pyrolysis temperature enhanced the electrical conductivity of the carbon support, thereby improving the ORR performance of the catalyst. However, while the defect density and specific surface area of the carbon support initially increased with increasing pyrolysis temperature, they declined when elevated temperatures were used (e.g., 1000 °C), leading to reduced ORR activity. The AC-900 support, pyrolyzed at 900 °C, exhibited an optimal balance of a high surface area, abundant defects, and superior conductivity. An Fe phthalocyanine/AC-900 catalyst synthesized using the AC-900 support exhibited excellent ORR activity (E1/2: 0.89 V and Eon: 0.95 V vs. reversible hydrogen electrode (RHE)) in 0.1 M KOH. This work highlights the pivotal role of carbon support microstructure in governing the ORR activity of the supported catalyst and provides a rational strategy for designing high-performance non-noble metal electrocatalysts. Full article
(This article belongs to the Section Energy and Catalysis)
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16 pages, 5596 KB  
Article
Unraveling the Mechanisms of Madecassoside Derivatives in Wound Healing: Network Pharmacology and Experimental Validation
by Jing Liu, Yuanyuan Li, Cheng Yang and Bingtian Zhao
Pharmaceuticals 2025, 18(9), 1292; https://doi.org/10.3390/ph18091292 - 28 Aug 2025
Viewed by 83
Abstract
Background: Madecassoside is widely utilized in wound healing due to its multiple physiological activities. However, its limited bioavailability and solubility hinder its clinical application. Enzymatic hydrolysis has been employed to enhance the bioavailability and bioactivity of natural products, but its potential for modifying [...] Read more.
Background: Madecassoside is widely utilized in wound healing due to its multiple physiological activities. However, its limited bioavailability and solubility hinder its clinical application. Enzymatic hydrolysis has been employed to enhance the bioavailability and bioactivity of natural products, but its potential for modifying madecassoside remains unexplored. Methods: In this study, we prepared MA1G and MA2G through enzymatic hydrolysis, inspired by the metabolic processes of madecassoside. Network pharmacology was employed to investigate the mechanisms of these madecassoside derivatives (MDs) in wound healing, and molecular docking was performed to evaluate their binding affinities. Transdermal permeation studies, scratch assays, and antioxidant and anti-inflammatory tests were conducted to characterize the biological properties and activities of MDs. Results: Network pharmacology identified TLR4, NF-κB, and STAT3 as key targets for wound healing, and the MDs inhibited the expression of these proteins in vitro. Additionally, the results demonstrated that MDs exhibited robust reactive oxygen species (ROS) scavenging activity (43.05–147.50% reduction) and significantly enhanced cell migration (36.76–77.28% increase). Notably, the biomodified MA2G showed superior transdermal permeability and biological activities. Conclusions: This paper represents the first report directly comparing the biological activities of the parent compound (madecassoside) and its metabolites while simultaneously proposing a novel therapeutic strategy for wound healing. Full article
(This article belongs to the Section Pharmacology)
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Article
The Effect of Aerobic Exercise Training on Patients with Type III Spinal Muscular Atrophy
by Sezan Mergen Kilic, Fatma Mutluay, Arman Cakar, Murat Giris, Hacer Durmus, Ilknur Bingul, Asuman Gedikbasi, Canan Kucukgergin, Zehra Oya Uyguner and Yesim Parman
J. Clin. Med. 2025, 14(17), 6087; https://doi.org/10.3390/jcm14176087 - 28 Aug 2025
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Abstract
Background: Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by variants in the SMN1 gene. This study investigates the functional and biochemical effects of moderate-intensity aerobic exercise in SMA Type III patients. Methods: Twenty-three patients aged 18–57 years were included in this [...] Read more.
Background: Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by variants in the SMN1 gene. This study investigates the functional and biochemical effects of moderate-intensity aerobic exercise in SMA Type III patients. Methods: Twenty-three patients aged 18–57 years were included in this study. The training group underwent a 12-week aerobic exercise program using a bicycle ergometer at 60–70% of their maximum heart rate three times per week for 30 min per session. The training continued for an additional four months. The primary outcome measures were the six-minute walk distance and oxygen uptake, both reflecting exercise capacity. Secondary outcome measures included muscle strength with dynamometer, functional performance, and fatigue with different scales. Furthermore, serum survival motor neuron (SMN) protein and insulin-like growth factor-1 (IGF-1) hormone levels were measured at baseline, post-training first measurement (after 12 weeks), and post-training second measurement (after 28 weeks). Results: The exercise group showed a significant increase in exercise capacity (p < 0.001) and 6MWT walking distance (p = 0.003). Furthermore, reduction in walking time in the 10-m walk test (p = 0.019) and improvements in strength of the right and left quadriceps (p = 0.004, p = 0.031) and right gastrocnemius (p = 0.034) muscles were identified. Furthermore, an improvement in the Fatigue Severity Scale (FSS) (p = 0.037) was found. SMN protein and IGF-1 levels were increased in the second measurement in the training group (p = 0.022 and p = 0.016, respectively). Conclusions: An aerobic exercise program improved physical function and muscle strength and reduced fatigue in SMA Type III patients, with sustained biochemical improvements. Aerobic exercise may serve as a beneficial adjunct therapy for this population. Full article
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