Search Results (182)

Purpose: We previously reported that the systemic administration of preprogrammed mouse hematopoietic bone marrow-derived progenitor cells (HSPCs) improved visual function and restored a functional retinal pigment epithelial (RPE) layer. Here, we investigated the potential impact of donor vs. host age on systemic cellular therapy in a murine model of retinal degeneration. Methods: HSPCs from young (8 weeks) and old (15 months) mice were programmed ex vivo with a lentiviral vector expressing the RPE65 gene (LV-RPE65) and systemically administering into young or old SOD2 KD mice. Visual loss and pathological changes were evaluated by electroretinogram (ERG), optical coherence tomography (OCT), histology, and immunohistochemistry. Results: Old donor HSPCs administered to old manganese superoxide dismutase (SOD2) knockdown (KD) recipient mice offered the least benefit. This was exemplified by the reduced recruitment and incorporation of LV-RPE65 HSPC into the RPE layer, as well as decreased improvement in visual function, retinal thinning, and limited reduction in oxidative damage and microglial activation. LV-RPE65 HSPC from young mice incorporated into the RPE layer of old SOD2 KD mice, though to a lesser extent than young cells administered to young hosts, offered some level of protection. By contrast, LV-RPE65 HSPCs from old mice, located to the subretinal space of young host mice, reduced visual loss, although some retinal pathology was observed. Conclusions: The administration of LV-RPE65 HSPC from old donors to old SOD2 KD mice offered the least improvement. Translational Relevance: Our findings highlight how both donor and recipient age impact the success of HSPC-based retinal therapy and using cells from aged donors for AMD treatment may have some limitations. Full article

Mitochondrial oxidative stress and neuroinflammation are involved in the onset and progression of Alzheimer’s disease (AD). Novel reliable, circulating biomarkers related to these processes were searched in cerebrospinal fluid (CSF) and plasma samples. Paired CSF and plasma samples from 20 subjective memory complaints (SMC) subjects, 20 mild cognitive impairment (MCI) due to AD subjects, and 20 Alzheimer’s dementia (ADd) patients were analyzed. Protein amounts of manganese-containing superoxide dismutase 2 (SOD2), cell-free mitochondrial DNA (cf-mtDNA) level, DNase I, and matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) activities were determined. As for SOD2, an MCI male-specific significant increase in both biofluids and an ADd male-specific significant decrease in plasma were found. No significant differences were demonstrated in cf-mtDNA level. An ADd-specific significant increase in plasma DNase I and MMP-2 activities was found. A SMC female-specific significant higher value in CSF MMP-9 activity in comparison to male counterparts was demonstrated. The present results suggest a male patient-specific (MCI and ADd) regulation of SOD2 expression in plasma and support an ADd-specific increase in plasma DNase I and MMP-2 activities. Therefore, the potential of SOD2 amount, DNase I, and MMP-2 activities in plasma as new markers of ADd should be explored. The SMC female-specific high activity of MMP-9 might contribute to AD female-sex bias. Full article

Wilson’s disease (WD) is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene. While hepatic manifestations are frequent, psychiatric symptoms occur in up to 30% of patients and may precede neurological signs. This study was the first to assess the relationship between oxidative stress, selected genetic polymorphisms, and psychiatric symptoms in WD. A total of 464 patients under the care of the Institute of Psychiatry and Neurology in Warsaw were studied. Genotyping for GPX1 (rs1050450), SOD2 (rs4880), and CAT (rs1001179) was performed, along with biochemical analyses of copper metabolism, oxidative DNA, lipid and protein damage, and systemic antioxidant capacity. Among the most important observations are the following: the homozygous GPX1 rs1050450 TT and SOD2 rs4880 CC genotypes were associated with the lowest prevalence of psychiatric symptoms. The CAT rs1001179 TT genotype was linked to a delayed onset of psychiatric symptoms by 6.0–8.5 years. Patients with or without psychiatric symptoms did not differ significantly in saliva 8-OHdG, total antioxidant capacity, serum glutathione (GSH), catalase, and MnSOD; however, patients reporting psychiatric symptoms had significantly higher prostaglandin F2α 8-epimer (8-iso-PGF2α) concentrations and tended to have lower serum glutathione peroxidase (Gpx) concentrations compared to those without such symptoms. Our data firstly provide consistent evidence that oxidative stress balance associated with copper overload in the CNS may be associated with CNS damage and the development of psychiatric symptoms of WD. In particular, our findings of increased oxidative lipid damage together with decreased Gpx activity indirectly suggest that damage to neuronal membrane lipids, which may be potentially related to abnormalities in GSH metabolism, may have an etiological role in CNS damage and related symptoms. Full article

Manganese superoxide dismutase (MnSOD) is a vital mitochondrial antioxidant enzyme that preserves cellular integrity by catalyzing the dismutation of superoxide radicals into hydrogen peroxide. Its central role in maintaining redox homeostasis has positioned it as a key target in biomedical research. This review provides an in-depth examination of MnSOD’s structural and functional properties, regulatory mechanisms, and its involvement in the pathogenesis of various human diseases. Full article

This study evaluated the effects of organic trace mineral supplementation on growth performance, antioxidant indices, mineral status, and diarrhea incidence in dairy calves raised in arid climates. Twenty-five male Holstein calves were randomly assigned to five dietary treatments for 21 days, as follows: (1) control group (no organic mineral supplementation), (2) copper-methionine (Cu-Met) supplemented diet, (3) zinc-methionine (Zn-Met) supplemented diet, (4) manganese-methionine (Mn-Met) supplemented diet, and (5) Zn-Met + Cu-Met + and Mn-Met in a premix supplemented diet. Mineral supplementation had no effect on final body weight or average daily gain. However, the concentrations of Zn, Cu, and Mn significantly increased (p < 0.01) in blood and feces of treated animals. The highest blood concentrations of Zn and Mn were observed in calves receiving Zn-Met, while Mn-Met supplementation significantly influenced blood Cu levels. The highest Zn excretion was recorded in calves receiving the organic mineral premix, whereas the highest Mn and Cu excretion was observed in the Cu-Met group. Additionally, mineral supplementation enhanced total antioxidant capacity and superoxide dismutase activity in plasma samples (p < 0.01). These findings suggest that organic mineral supplementation could be an effective strategy to improve mineral bioavailability and support the health of dairy calves during early life in arid climates. Full article

Soybean is one of the main agricultural commodities, and its productivity is limited by several diseases, such as anthracnose, which is caused by a complex of fungal species, with Colletotrichum truncatum being the most prevalent. Management is mainly carried out through chemical seed treatment. However, a reduction in the sensitivity of C. truncatum to fungicides was observed. Therefore, it is extremely important to search for products that are effective in controlling the disease. The objectives of this study were to evaluate the efficacy of commercial formulations of copper, potassium, manganese, and zinc phosphites in the treatment of soybean seeds infected by C. truncatum, as well as their direct fungitoxicity and ability to induce soybean defense mechanisms. For this purpose, seeds inoculated with C. truncatum were subjected to phosphites and a fungicide (carbendazim + thiram). The seeds were exposed to germination, health, and vigor tests. Fungal toxicity and the ability of phosphites to induce defense through the activities of catalase, peroxidase, and superoxide dismutase enzymes, as well as the levels of lignin and total soluble phenols, were also evaluated. Mn and Zn phosphites showed direct toxicity to C. truncatum and were as effective as the fungicide (carbendazim + thiram) in treating soybean seeds infected by the fungus. Mn phosphite induced the production of catalase (CAT), peroxidase (POX) and lignin, while Zn phosphite increased the production of CAT and POX. These results demonstrate the efficacy of Mn and Zn phosphites in controlling C. truncatum in infected soybean seeds, their direct toxic action, and their ability to induce resistance. Full article

Manganese (Mn) is an essential trace element and a cofactor for several key enzymes, such as mitochondrial superoxide dismutase. Consequently, it plays an important defense role against reactive oxygen species. Despite this, Mn chronic overexposure can result in a neurological disorder referred to as manganism, which shares some similarities with Parkinson’s disease. Mn levels seem regulated by many transporters responsible for its uptake and efflux. These transporters play an established role in many inherited disorders of Mn metabolism and neurotoxicity. Some inherited Mn metabolism disorders, caused by mutations of SLC30A10 and SLC39A14, assume crucial importance since earlier treatment results in a better prognosis. Physicians should be familiar with the clinical presentation of these disorders as the underlying cause of dystonia/parkinsonism and look for other accompanying features, such as liver disease and polycythemia, which are typically associated with SLC30A10 mutations. This review aims to highlight the currently known Mn transporters, Mn-related neurotoxicity, and its consequences, and it provides an overview of inherited and acquired disorders of Mn metabolism. Currently available treatments are also discussed, focusing on the most frequently encountered presentations. Full article

Rheumatoid arthritis (RA) is a long-term systemic autoimmune disorder that causes joint inflammation, swelling, pain, bone erosion, and deformities. Recent findings emphasize the anti-inflammatory and antioxidant properties of bioactive natural compounds, such as polyphenols extracted from plants and fruits, and their possible synergistic effect when used in combination with current therapies to improve the prognosis and symptoms of inflammatory rheumatic diseases. Here, we report that Sicilian extra virgin olive oil polyphenol-enriched extracts (PE-EVOOs) reduce intracellular reactive oxygen species (ROS) and pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β), in peripheral mononuclear cells (PBMCs) obtained from both RA patients and healthy subjects (HSs) treated with lipopolysaccharides (LPS) as a control. HPLC-ESI-MS analysis highlighted that PE-EVOOs are rich in different polyphenolic compounds responsible for many of the observed biological effects. At molecular levels, Western blotting analyses revealed that PE-EVOO treatment is associated with the downregulation of the phosphorylated and active form of the inflammatory transcription factor NF-κB and the pro-inflammatory enzyme cyclooxygenase 2 (COX2). In addition, PE-EVOOs upregulated the transcription factor Nrf2 and its target antioxidant enzyme catalase and manganese superoxide dismutase (MnSOD). Collectively, these results suggest a possible use of PE-EVOOs as potential adjuvants for the treatment of RA. Full article

Ionizing radiation is a health threat to many, including warfighters, radiological emergency responders, radiotherapy patients, and astronauts. Despite this, no FDA-approved prophylactic medical countermeasures exist to attenuate the symptoms that occur from radiation exposure. Manganese has recently been shown to be critical for radioresistance in a wide range of organisms. In this study, we designed a stringent feeding method to test the prophylactic effects of dietary manganese on Drosophila’s lifespan before exposure to acute irradiation. We found that male flies have substantially lower radioresistance than females, but feeding with low doses of MnCl₂ before acute irradiation exposure extends male survival to that of females. Whole animal electron paramagnetic resonance analyses showed males have lower amounts of high-symmetry manganese-metabolite antioxidant complexes (H-Mn) than females, but manganese supplementation increases H-Mn to female levels. Levels of mitochondrial free-radical scavenger manganese-superoxide-dismutase 2 (MnSOD2) did not increase after acute irradiation, nor did loss of MnSOD2 sensitize larvae to acute irradiation exposure. These data support that prophylactic manganese feeding is sufficient to increase survivorship in males subjected to acute irradiation, independent of MnSOD2 levels, indicating a role of antioxidant manganese-metabolite H-Mn complexes for radioprotection. Furthermore, this Drosophila feeding method could be used to identify additional radiation countermeasures. Full article

Aluminum (Al) toxicity in acidic soils poses significant challenges to crop growth and development. However, the response mechanism of Shatian pomelo (Citrus maxima ‘Shatian Yu’) roots to Al toxicity remains poorly understood. This study employed root phenotype analysis, physiological response index measurement, root transcriptome analysis, and quantitative PCR (qPCR) validation to investigate the effects of Al toxicity on Shatian pomelo roots. The findings revealed that Al toxicity inhibited root growth and development, resulting in reduced root biomass, total root length, total root surface area, root volume, average root diameter, and root tip count. Antioxidant enzyme activities (peroxidase, superoxide dismutase, ascorbate peroxidase, and catalase activity) and soluble protein content increased with rising Al toxicity, whereas malondialdehyde content initially increased and then declined. Additionally, Al toxicity stress increased Al (1439.25%) content and decreased boron (B, 50.64%), magnesium (Mg, 42.04%), calcium (Ca, 46.02%), manganese (Mn, 86.75%), and iron (Fe, 69.92%) levels in the roots. RNA sequencing (RNA-seq) analysis identified 3855 differentially expressed genes (DEGs) between 0 mmol/L Al (control) and 4 mmol/L Al (Al toxicity) concentrations, with 1457 genes up-regulated and 2398 down-regulated, indicating a complex molecular regulatory response. The qPCR results further validated these findings. This study elucidates the response mechanisms of Shatian pomelo roots to Al toxicity stress, providing insights into the regulatory pathways involved. The findings offer valuable reference points for breeding Al-resistant Shatian pomelo varieties. The results of this study provide important genetic tools and technical support for the screening and breeding of highly resistant varieties of Shatian pomelo. On the one hand, by detecting the key indexes (such as antioxidant enzyme activity and nutrient absorption capacity) of Shatian pomelo, varieties with excellent anti-Al toxicity characteristics can be selected. On the other hand, the Al-resistant genes identified in this study, such as TFM1 and ALERTFA0, can be used to develop molecular markers, assisted marker breeding, or transgenic breeding to accelerate the breeding process of Al-resistant strains. Full article

White tea has been scientifically proven to exhibit positive biological effects in combating chronic diseases, including cancer, metabolic syndrome, etc. Nevertheless, the anti-aging activity and mechanism of white tea on organisms exposed to a high-fat diet remain unexplored. Herein, we prepared a white tea aqueous extract (WTAE) from white peony in Fuding and assessed its in vivo antioxidant and anti-aging effects by employing a Drosophila melanogaster senescence model induced by lard, delving into the underlying molecular mechanisms through which the WTAE contributes to lifespan improvement. Notably, the WTAE significantly extended the lifespan of Drosophila fed a high-fat diet and partially restored the climbing ability of Drosophila on a high-fat diet, accompanied by increased activities of copper-zinc superoxide dismutase, manganese-superoxide dismutase, and catalase and decreased lipid hydroperoxide levels in Drosophila. Furthermore, transcriptomic analysis indicated that the WTAE countered aging triggered by a high-fat diet via activating oxidative phosphorylation, neuroactive ligand–receptor interactions, and more pathways, as well as inhibiting circadian rhythm-fly, protein processing in the endoplasmic reticulum, and more pathways. Our findings suggest that WTAE exhibits excellent inhibitory activity against high-fat diet-induced senescence and holds promising potential as an anti-aging agent that can be further developed. Full article

Manganese is one of the trace elements necessary for organisms to maintain normal biological activities and is also a cofactor for manganese superoxide dismutase (Mn-SOD) and manganese peroxidase (MnP). In order to find a simple and effective method to rejuvenate the degenerated V. volvacea strains, we explored the effect of the exogenous addition of MnSO₄ on the antioxidant vigour and productivity of degenerated strains of V. volvacea. The results showed that the exogenous MnSO₄ had no significant effect on the non-degenerated strain T0, but it could effectively increase the mycelial growth rate, mycelial biomass, and LBL decolouring ability of the degenerated strains T10 and T19, and reduce the production cycle and increased the biological efficiency of T10; it helped the severely degenerated T19 to regrow its fruiting body; and it also significantly increased the viability of the matrix-degrading enzymes such as EG, Lac, Xyl, etc. of T10 and T19. Meanwhile, exogenous MnSO₄ significantly increased the activity of GPX, GR, CAT, SOD, and the content of GSH, polyphenols, minerals, and polysaccharides in T10 and T19 strains, which resulted in a significant decrease in the accumulation of ROS, such as O₂⁻ and H₂O₂ in T10 and T19. The correlation analysis showed that there was a significant correlation between antioxidant activity and the production ability of V. volvacea. This study can provide theoretical reference and technical support for the rejuvenation research of degenerated strains of V. volvacea and other edible fungi. Full article

The importance of manganese superoxide dismutase (Mn-SOD), an evolutionarily ancient metalloenzyme that maintains the integrity and function of mitochondria, was studied in oxidative stress-treated Aspergillus fumigatus cultures. Deletion of the Mn-SOD gene (sodB) increased both the menadione sodium bisulfite (MSB)-elicited oxidative stress and the deferiprone (DFP)-induced iron limitation stress sensitivity of the strain. Moreover, DFP treatment enhanced the MSB sensitivity of both the gene deletion mutant and the reference strain. The lack of SodB also increased the susceptibility of conidia to killing by human macrophages. Concurring with the stress sensitivity data, RNS sequencing data also demonstrated that the deletion of sodB largely altered the MSB-induced oxidative stress response. The difference between the oxidative stress responses of the two strains manifested mainly in the intensity of the response. Importantly, upregulation of “Ribosome protein”, “Iron uptake”, and “Fe-S cluster assembly” genes, alterations in the transcription of “Fe-S cluster protein” genes, and downregulation of “Heme binding protein” genes under MSB stress were characteristic only for the ΔsodB gene deletion mutant. We assume that the elevated superoxide level generated by MSB treatment may have destroyed Fe-S cluster proteins of mitochondria in the absence of SodB. This intensified the resynthesis of Fe-S cluster proteins, which was accompanied with enhanced translation and iron acquisition, leading to increased DFP sensitivity. Full article

Reactive oxygen species (ROS) are double-edged swords in biological systems—they are essential for normal cellular functions but can cause damage when accumulated due to oxidative stress. Manganese superoxide dismutase (MnSOD), located in the mitochondrial matrix, is a key enzyme that neutralizes superoxide radicals (O₂^•−), maintaining cellular redox balance and integrity. This review examines the development and therapeutic potential of MnSOD mimetics—synthetic compounds designed to replicate MnSOD’s antioxidant activity. We focus on five main types: Mn porphyrins, Mn salens, MitoQ10, nitroxides, and mangafodipir. These mimetics have shown promise in treating a range of oxidative stress-related conditions, including cardiovascular diseases, neurodegenerative disorders, cancer, and metabolic syndromes. By emulating natural antioxidant defenses, MnSOD mimetics offer innovative strategies to combat diseases linked to mitochondrial dysfunction and ROS accumulation. Future research should aim to optimize these compounds for better stability, bioavailability, and safety, paving the way for their translation into effective clinical therapies. Full article

Saline soils, as a special class of soil types, have unique physicochemical properties that have far-reaching effects on crop growth and quality characteristics. In order to better develop saline soils as a reserve resource, it is particularly important to exploit the potential of saline crops. Peanut, as one of the important crops in saline soils, can have different quality characteristics depending on the differences in soil salinity and alkalinity, as well as growing conditions. In this study, we compared the nutritional quality and functional composition of five peanut varieties grown in coastal saline soils, with the same varieties grown in non-saline soils in similar areas. The results showed significant differences ($p<0.05$) between saline and non-saline peanuts in the contents of ash, zinc, phosphorus, $\beta$-VE, Cis-11-eicosatetraenoic acid, palmitoleic acid, linolenic acid, and total antioxidant removal capacity, whereby the former was higher than the latter by 0.12 g/100 g, 4.1 mg/kg, 321 mg/kg, 8.98 μg/g, 0.36%, 0.01%, and 0.01%, respectively, and the total antioxidant capacity was lower than that of the latter by 9.18 $\mathsf{\mu }$g Trolxo/g of fresh weight. Sodium element and superoxide dismutase (SOD) activity contents were extremely significantly ($p<0.01$) different in peanuts grown in both land types, where the former was higher than the latter by 261.9 mg/kg and 285 U/g, respectively. Water, fat, protein, calcium, copper, iron, potassium, magnesium, manganese, Vc, $\alpha$-VE, total VE, VB3, 5-methyl-tetrahydrofolate, 5-formyl-tetrahydrofolate, total phenols, total flavonoids, ABTS free radical scavenging capacity, DPPH free radical scavenging capacity, fatty acids (except for Cis-11-eicosapentaenoic acid, palmitoleic acid, and linolenic acid), phytosterols, and guanines showed no significant differences ($p<0.01$). To sum up, the origin and soil environment have an effect on the quality of peanuts. These results also provide a scientific basis for the quality assessment of peanuts in saline soil. Full article