Free Radical Research最新文献

In this study, the anti-aging potential of melibiose was examined, and its molecular mechanism was elucidated using Caenorhabditis elegans as a model organism. The findings demonstrated that melibiose at concentrations of 100 μM, 150 μM, and 200 μM significantly increased nematode lifespan by 15.38%, 23.08%, and 30.77% respectively. Additionally, melibiose enhanced resistance against heat and oxidative stress, improved nematode motility, reduced lipofuscin and reactive oxygen species (ROS) accumulation, and increased antioxidant enzyme activity. Through the use of gene-deletion nematodes, transgenic nematodes, RT-qPCR, and metabolomics, it was determined that melibiose potentially exerts its effects through multiple pathways including the insulin signaling pathway (down-regulation of daf-2 and age-1, up-regulation of sod-3 and hsp-16.2), the AMP-activated protein kinase (AMPK) pathway (up-regulation of aak-2), and the JNK pathway (up-regulation of jnk-1). Activation of transcription factors DAF-16, SKN-1, and HSF-1 was observed, moreover, delaying the aging process by promoting autophagy (upregulation of lgg-1 and bec-1) and mitochondrial function (upregulation of hsp-6, hsp-60, and mev-1) to resist oxidative damage. And its anti-aging signature metabolites may be Carbimazole, 4-Hydroxy-2-oxoglutaric acid, and 1,4-Dithiothreitol.

Far-infrared radiation (FIR) induces glutathione peroxidase-1 (GPx-1) expression and enhances microcirculation by upregulating endothelial nitric oxide synthase (eNOS). However, the role of eNOS in FIR-mediated neuroprotection remains unclear. Here, we investigated whether FIR upregulates eNOS and extracellular signal-regulated kinase (ERK) signaling to mitigate recognition memory impairment caused by methamphetamine (MA). FIR significantly reduced MA-induced oxidative stress, which was primarily associated with GPx-1 inhibition. FIR or genetic overexpression of GPx-1 (GPx-1 TG) in mice significantly attenuated the MA-induced reduction in phospho-eNOS (p-eNOS) and phospho-ERK (p-ERK). Triple-label immunostaining revealed colocalization of p-eNOS, p-ERK, and GPx-1 within the same cellular populations in the prefrontal cortex. In non-transgenic (non-TG) mice, FIR exposure improved MA-induced cholinergic and memory deficits. However, FIR did not provide additional cognitive benefits in GPx-1 TG mice, and the GPx-1 inhibitor mercaptosuccinate blocked FIR-mediated cholinergic effects. Inhibitors of eNOS (i.e. L-NAME) and ERK (i.e. U0126) also significantly blocked the FIR-driven memory-enhancing effects in non-TG mice. Unlike L-NAME, which inhibits phosphorylation of both eNOS and ERK, U0126 did not affect FIR-induced eNOS phosphorylation, suggesting that eNOS is an upstream molecule for ERK signaling. Our finding suggests that GPx-1 is an essential mediator of FIR-induced memory enhancement, and that FIR exposure attenuates MA-induced cognitive impairments via cholinergic upregulation associated with GPx-1/eNOS/ERK signaling.

Perturbation in redox status elicits multiple cellular pathways, including those involved in the inflammatory response. A thiol-based molecule (I-152), releasing N-acetyl-cysteine (NAC) and β-mercaptoethylamine (MEA), was exploited as a redox-modulating agent, and its effects on pro-inflammatory cytokine expression and secretion in lipopolysaccharide (LPS)-stimulated macrophages (MΦ) were investigated. I-152 inhibited cytokine gene expression as well as protein secretion of the most important inflammatory cytokines in three different MΦ models in vitro and ex vivo. It alleviated inflammation via the c-Jun/AP-1 and NF-κB signaling pathways, depending on the dose, and regulated NLRP3 inflammasome expression, leading to decreased IL-1β and IL-18 release and reduced pyroptotic cell death. Consequently, the influence of redox-modulated MΦ secretome on the crosstalk with endothelial cells was evaluated. Co-culture experiments between THP-1 MΦ, that had been pretreated with I-152 before LPS stimulation, and Human Vascular Endothelial Cells (HUVECs) showed reduced VCAM/ICAM expression in these cells in concomitance with a less oxidized and inflamed MΦ proteomic portrait. Overall, our findings suggest that I-152 redox modulation could target the AP-1/NLRP3 axis, affecting LPS-induced inflammation in MΦ and influencing HUVEC responses, revealing a complex and bidirectional interchange.

The antioxidant properties of 34 plant alkaloids in gas phase, ethanol and water have been evaluated using density functional theory (DFT). The computations have been made according to three different single electron mechanisms: (1) H-atom transfer (HAT); (2) electron transfer followed by H⁺ transfer (SET-PT); and (3) sequential H⁺-loss electron transfer (SPLET). As a result, the highest antioxidant activity was established for evodiamine. Global reactivity in terms of hardness/softness has been calculated also, as well as Fukui indices of local reactivity. Structural aspects related to H, electron and proton loss have been regarded in sufficient details. In terms of global softness, palmatine, dehydroevodiamine and chelerythrine have been determined as the most reactive molecules, whereas C7 atom of evodiamine has been found to be the most reactive atom. All the findings are in agreement with the recent experimental and theoretical studies on alkaloid antioxidant activity and can be compared with the results for ascorbic acid, which was used as a reference compound.

Atmospheric pressure low-temperature plasma treatment has been shown to enhance seed germination in various plant species. However, whether plasma treatment modulates seed dormancy status or affects the seed germination process remains unclear. Additionally, most studies have primarily focused on the positive effects of plasma on germination and growth, without addressing dose-dependent responses or underlying molecular mechanisms. To elucidate the effects of plasma treatment on seed germination at a molecular level, we analyzed the germination phenotype of fully ripened Arabidopsis thaliana seeds under germination-inhibitory conditions following plasma treatment. We observed that plasma treatment enhanced germination potential up to a critical threshold, beyond which prolonged treatment diminished the enhanced effect. Chemical staining assays identified that plasma treatment induced the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) at different time points. Machine-learning aided modeling revealed that ROS, rather than RNS, plays a key role in plasma-mediated germination induction. Furthermore, transcriptome analyses suggested candidate genes likely modulated by plasma treatment during seed germination, including glutathione and L-phenylalanine metabolism, abscisic acid signaling, and the tricarboxylic acid cycle. Our study provides the first molecular-level insights into how atmospheric pressure low-temperature plasma modulates seed germination.

Acute poisoning remains a significant cause of admission to the emergency intensive-care unit (EICU). Despite a reduced mortality rate, attention is increasingly focusing on the impact of post-intensive-care syndrome (PICS) on readmission. Due to the significant role of oxidative stress (OS) in the pathological mechanisms of poisoning, 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) may hold great potential as biomarkers for OS biomarkers to evaluate the severity and prognosis of poisoning. Therefore, we investigated the longitudinal changes of urinary 8-oxoGuo levels during hospitalization in poisoned patients, their association with organ failure, and their predictive value for 30-day readmission risk. In total, 43 poisoning patients were enrolled from the EICU of the First Affiliated Hospital of Wenzhou Medical University between July 2021 and November 2022. The 30-day readmission rate was 18.6%. Group-based trajectory modeling (GBTM) was used to explore the potential trajectories of urinary OS markers and organ failure scores during hospitalization. Spearman's correlation analysis revealed a significant association between a high trajectory of 8-oxoGuo/creatinine (Cr) and the increased severity of overall organ failure, as well as respiratory and coagulation dysfunctions. Binary logistic regression analysis indicated that a high 8-oxoGuo/Cr trajectory, high respiratory failure score trajectory, and 8-oxoGuo/Cr values at three key points in disease progression (including admission, transfer from EICU, and discharge), along with 8-oxodGuo/Cr levels at admission, were all risk factors for 30-day readmission. The 8-oxoGuo/Cr value at discharge exhibited the best predictive performance. The urinary 8-oxoGuo/Cr ratio may serve as a potential biomarker for prognostic evaluations in patients with poisoning.

Macrophages and neutrophils are the main immune cells of the acute stage of inflammation. Upon their activation, membrane-bound NADPH oxidase produces superoxide anion radical, which is converted to H₂O₂ by superoxide dismutase (SOD). In this study, we compared the production of hydrogen peroxide by two phenotypes of pro-inflammatory human M1 macrophages and neutrophils activated with phorbol-12-myristate 13-acetate. Macrophages were obtained from blood monocytes (monocyte-derived macrophages (MDM)) differentiated into MDM using GM- or M-CSF growth factors and polarized into the M1 state, receiving GM_M1, M_M1, respectively. The total level of H₂O₂ production measured in the presence of horseradish peroxidase differed significantly between two types of macrophages. Only GM_M1 macrophages had a level of H₂O₂ production comparable to neutrophils. GM_M1 appear at the site of inflammation after neutrophils, they continue the work of neutrophils in creating a pro-inflammatory environment: they produce several times more H₂O₂ and pro-inflammatory cytokines than M_M1, which arrive at inflammatory site later. Upon activation, MDM_M1 formed big blot-like and smaller dense spheroid-like aggregates. Activated neutrophils secrete the enzyme myeloperoxidase (MPO), which synthesizes the very potent oxidant hypochlorous acid (HOCl) only in the presence of H₂O₂. Neutrophils are short lived cells, MPO can use H₂O₂ produced by activated cultured MDM to synthesize HOCl at physiologically relevant concentrations to prolong oxidative stress.

To develop a simple and sensitive method for assessing the radical-scavenging activity of lipophilic antioxidants, the decay of the electron spin resonance (ESR) signal of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl radical (TEMPOL) was investigated as an indicator of radical reactions. The ESR signal of TEMPOL was decreased in ethanol, but not in acetonitrile, by the pyrolysis of 2,2'-azobis(2,4-dimethylvaleronitrile). Signal decay in ethanol was suppressed by degassing and did not occur in the presence of the spin trapping agent 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide (DEPMPO). Spin trapping with DEPMPO showed the formation of peroxyl, alkoxyl, and alkyl radical adducts during the reaction, with peroxyl radical adducts decreasing in the presence of TEMPOL. These results indicate that TEMPOL signal decay occurs by reactions involving ethanol-derived peroxyl radicals. The TEMPOL signal decay was remarkably inhibited by 0.01 mmol/L 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), which is lower than the Trolox concentration used in the ESR-spin trapping method reported previously. Inhibition by methyl gallate was markedly stronger than Trolox, while the effects of 2,6-di-tert-butyl-p-cresol and resveratrol were minor. The order of inhibition of TEMPOL signal decay by antioxidants correlated to some extent with the order of suppression of peroxyl radical adduct formation by DEPMPO spin trapping. Therefore, the peroxyl radical-scavenging activities of lipid-soluble antioxidants may be evaluated with high sensitivity by examining the inhibitory activity of TEMPOL decay caused by radical reactions in ethanol. The measurement time was less than 5 min.

Sinensetin (SIN for short) is one of the most common polymethoxyflavonoids found in citrus fruits. Recently, it has been extensively studied due to its ability to prevent or treat a wide range of diseases, including diabetes, obesity, neurological disorders, and cancer. Oxidative stress is closely related to the pathogenesis of many diseases. Based on literature research and the results of our previous experiments, we found that flavonoids have significant antioxidant effects. This study found that sinensetin alleviated AAPH-induced oxidative stress in zebrafish and alleviated intestinal and brain damage (including brain neurons, vascular development, and blood-brain barrier integrity). This study is of great significance for further study of the relationship between gut-brain changes and oxidative stress. This study provides a practical and convenient tool for real-time tracking of the protective effect of natural products on the in vivo oxidative stress model induced by AAPH. In addition, it paves the way for the discovery of more antioxidants in the future.

The prognosis of gastric cancer (GC) remains poor due to metastases and resistance to chemotherapy. Ferroptosis is a novel cell death regulation mode characterized by iron dependence and lipid peroxidation. Dioscin, a compound extracted from the Paris polyphylla rhizomes roots, has been shown to have an inhibitory effect on cancers. However, whether it induces ferroptosis to participate in anti-cancer metastasis remains unclear. The ability of gastric cancer cells to invade and migrate was evaluated by wound healing and transwell assays. Malondialdehyde (MDA), glutathione (GSH) assay kit, and dichlorofluorescin diacetate (DCFH-DA) fluorescent probes were used to detect ferroptosis in gastric cancer cells. The expression levels of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot methods. The rescue assay was performed by adding Ferrostatin-1 (Fer-1) co-treatment to verify that Dioscin inhibited gastric cancer metastasis by participating in ferroptosis. Dioscin inhibited gastric cancer cells' wound healing, migration, and invasion process. In addition, Dioscin increased the level of reactive oxygen species (ROS) and MDA while decreasing GSH level, and induced ferroptosis of gastric cancer cells. Fer-1, an inhibitor of ferroptosis, could reverse the effect of Dioscin. In terms of mechanism, Dioscin induced ferroptosis through SLC7A11/GPX4 axis and was involved in the regulation of inhibiting metastasis of gastric cancer. These results suggested that Dioscin was involved in anti-cancer metastasis by inducing ferroptosis.