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Advanced Science (Weinheim,... Dec 2023Malignant tumors pose a serious risk to human health. Ascorbic acid (AA) has potential for tumor therapy; however, the mechanism underlying the ability of AA to...
Malignant tumors pose a serious risk to human health. Ascorbic acid (AA) has potential for tumor therapy; however, the mechanism underlying the ability of AA to selectively kill tumor cells remains unclear. AA can cause redox disequilibrium in tumor cells, resulting in the release of abundant reactive oxygen species, represented by hydrogen peroxide (H O ). Therefore, the detection of H O changes can provide insight into the selective killing mechanism of AA against tumor cells. In this work, inspired by the ion-exchange mechanism in coral formation, a flexible H O sensor (PtNFs/CoPi@CC) is constructed to monitor the dynamics of H O in the cell microenvironment, which exhibits excellent sensitivity and spatiotemporal resolution. Moreover, the findings suggest that dehydroascorbic acid (DHA), the oxidation product of AA, is highly possible the substance that actually acts on tumor cells in AA therapy. Additionally, the intracellular redox disequilibrium and H O release caused by DHA are positively correlated with the abundance and activity of glucose transporter 1 (GLUT1). In conclusion, this work has revealed the potential mechanism underlying the ability of AA to selectively kill tumor cells through the construction and use of PtNFs/CoPi@CC. The findings provide new insights into the clinical application of AA.
Topics: Humans; Ascorbic Acid; Oxidation-Reduction; Reactive Oxygen Species; Hydrogen Peroxide; Neoplasms
PubMed: 37943018
DOI: 10.1002/advs.202304079 -
Talanta Feb 2024Ultrasensitive analytical methods are still urgent for the discovery of trace level biomarkers and the early clinical diagnosis of disease. In this work, an...
Ultrasensitive analytical methods are still urgent for the discovery of trace level biomarkers and the early clinical diagnosis of disease. In this work, an ultrasensitive universal sensing platform was constructed by integrating fluorescent assay with chemical-chemical redox cycling signal amplification strategy. Using Ru@SiO nanoparticles wrapped by MnO nanosheets (Ru@SiO@MnO) as fluorescent probe, the chemical-chemical redox cycling system was conducted upon ascorbic acid (AA) and tris(2-carboxyethyl)phosphine (TCEP) as reductants and MnO nanosheets as oxidant. The MnO nanosheets not only could quench the fluorescence of Ru@SiO nanoparticles to reduce the background, but also could serve as oxidants to react with AA, generating dehydroascorbic acid (DHA). The DHA was reduced by TCEP in turn to form AA that participated in the next cycling of chemical-chemical redox reaction. Thus, the constantly released AA from the chemical-chemical redox cycling system could massively etch MnO nanosheets on Ru@SiO surface, making the fluorescence of Ru@SiO nanoparticles greatly recovered. It was shown that the sensitivity of the fluorescent assay was improved almost 52 times by utilizing the chemical-chemical redox cycling signal amplification strategy. This strategy was further employed to detect DNA methylation with the aid of AA-encapsulated liposomes that were modified with 5 mC antibodies to bind with the methylated DNA captured in 96-well plate. A detection of limit down to 16.2 fM was achieved for the detection of methylated DNA. It's believed that the incorporation of chemical-chemical redox cycling signal amplification strategy into fluorescent sensing paves a new way for ultrasensitive detection of biomarkers.
Topics: Oxides; Manganese Compounds; DNA Methylation; Silicon Dioxide; Oxidation-Reduction; Ascorbic Acid; Limit of Detection; DNA; Biomarkers; Biosensing Techniques
PubMed: 37906997
DOI: 10.1016/j.talanta.2023.125363 -
The Analyst Nov 2023Affinity assays allow direct detection of DNA methylation events without requiring a special sequence. However, the signal amplification of these methods heavily depends...
Affinity assays allow direct detection of DNA methylation events without requiring a special sequence. However, the signal amplification of these methods heavily depends on nanocatalysts and bioenzymes, making them suffer from low sensitivity. In this work, alkaline phosphatase (ALP)-assisted chemical redox cycling was employed to amplify the sensitivity of fluorescence affinity assays for DNA methylation detection using Ru@SiO@MnO nanocomposites as fluorescent probes. In the ALP-assisted chemical redox cycling reaction system, ALP hydrolyzed 2-phosphate-L-ascorbic acid trisodium salt (AAP) to produce AA, which could reduce MnO nanosheets to form Mn, making the fluorescence recovery of Ru@SiO nanoparticles possible. Meanwhile, AA was oxidized to dehydroascorbic acid (DHA), which was re-reduced by tris(2-carboxyethyl) phosphine (TCEP) to trigger a redox cycling reaction. The constantly generated AA could etch large amounts of MnO nanosheets and greatly recover Ru@SiO fluorescence, amplifying the signal of the fluorescence assay. Employing the proposed ALP-assisted chemical redox cycling signal amplification strategy, a sensitive affinity assay for DNA methylation detection was achieved using ALP encapsulated liposomes that were linked with the 5mC antibody (Ab) to bind with methylated sites. A detection limit down to 2.9 fM was obtained for DNA methylation detection and a DNA methylation level as low as 0.1% could be distinguished, which was superior to conventional affinity assays. Moreover, the affinity assays could detect DNA methylation more specifically and directly, implying their great potential for the analysis of tumor-specific genes in liquid biopsy.
Topics: Alkaline Phosphatase; DNA Methylation; Fluorescence; Manganese Compounds; Silicon Dioxide; Oxides; Oxidation-Reduction
PubMed: 37842979
DOI: 10.1039/d3an01383a -
BMC Plant Biology Sep 2023Salt stress is one of the key factors limiting rice production. Alginate oligosaccharides (AOS) enhance plant stress resistance. However, the molecular mechanism...
BACKGROUND
Salt stress is one of the key factors limiting rice production. Alginate oligosaccharides (AOS) enhance plant stress resistance. However, the molecular mechanism underlying salt tolerance in rice induced by AOS remains unclear. FL478, which is a salt-tolerant indica recombinant inbred line and IR29, a salt-sensitive rice cultivar, were used to comprehensively analyze the effects of AOS sprayed on leaves in terms of transcriptomic and metabolite profiles of rice seedlings under salt stress.
RESULTS
In this experiment, exogenous application of AOS increased SOD, CAT and APX activities, as well as GSH and ASA levels to reduce the damage to leaf membrane, increased rice stem diameter, the number of root tips, aboveground and subterranean biomass, and improved rice salt tolerance. Comparative transcriptomic analyses showed that the regulation of AOS combined with salt treatment induced the differential expression of 305 and 1030 genes in FL478 and IR29. The expressed genes enriched in KEGG pathway analysis were associated with antioxidant levels, photosynthesis, cell wall synthesis, and signal transduction. The genes associated with light-trapping proteins and RLCK receptor cytoplasmic kinases, including CBA, LHCB, and Lhcp genes, were fregulated in response to salt stress. Treatment with AOS combined with salt induced the differential expression of 22 and 50 metabolites in FL478 and IR29. These metabolites were mainly related to the metabolism of amino and nucleotide sugars, tryptophan, histidine, and β -alanine. The abundance of metabolites associated with antioxidant activity, such as 6-hydroxymelatonin, wedelolactone and L-histidine increased significantly. Combined transcriptomic and metabolomic analyses revealed that dehydroascorbic acid in the glutathione and ascorbic acid cycles plays a vital role in salt tolerance mediated by AOS.
CONCLUSION
AOS activate signal transduction, regulate photosynthesis, cell wall formation, and multiple antioxidant pathways in response to salt stress. This study provides a molecular basis for the alleviation of salt stress-induced damage by AOS in rice.
Topics: Transcriptome; Seedlings; Antioxidants; Oryza; Salt Stress; Glutathione; Oligosaccharides
PubMed: 37770835
DOI: 10.1186/s12870-023-04470-x -
Biomimetics (Basel, Switzerland) Sep 2023This study focuses on developing and evaluating two novel enantioselective biomimetic models for the active centers of oxidases (ascorbate oxidase and catalase). These...
Enantioselective Biomimetic Structures Inspired by Oxi-Dase-Type Metalloenzymes, Utilizing Polynuclear Compounds Containing Copper (II) and Manganese (II) Ions as Building Blocks.
This study focuses on developing and evaluating two novel enantioselective biomimetic models for the active centers of oxidases (ascorbate oxidase and catalase). These models aim to serve as alternatives to enzymes, which often have limited action and a delicate nature. For the ascorbate oxidase (AO) model (compound ), two enantiomers, S,S(+)cpse and R,R(-)cpse, were combined in a crystalline structure, resulting in a racemic compound. The analysis of their magnetic properties and electrochemical behavior revealed electronic transfer between six metal centers. Compound effectively catalyzed the oxidation of ascorbic to dehydroascorbic acid, showing a 45.5% yield for the racemic form. This was notably higher than the enantiopure compounds synthesized previously and tested in the current report, which exhibited yields of 32% and 28% for the S,S(+)cpse and R,R(-)cpse enantiomers, respectively. This outcome highlights the influence of electronic interactions between metal ions in the racemic compound compared to pure enantiomers. On the other hand, for the catalase model (compound ), both the compound and its enantiomer displayed polymeric properties and dimeric behavior in the solid and solution states, respectively. Compound proved to be effective in catalyzing the oxidation of hydrogen peroxide to oxygen with a yield of 64.7%. In contrast, its enantiomer (with R,R(-)cpse) achieved only a 27% yield. This further validates the functional nature of the prepared biomimetic models for oxidases. This research underscores the importance of understanding and designing biomimetic models of metalloenzyme active centers for both biological and industrial applications. These models show promising potential as viable alternatives to natural enzymes in various processes.
PubMed: 37754174
DOI: 10.3390/biomimetics8050423 -
Cell Death & Disease Sep 2023Since the discovery of ferroptosis, it has been postulated that this type of cell death could be utilized in treatments for cancer. Unfortunately, several highly...
Since the discovery of ferroptosis, it has been postulated that this type of cell death could be utilized in treatments for cancer. Unfortunately, several highly aggressive tumor models are resistant to the pharmacological induction of ferroptosis. However, with the use of combined therapies, it is possible to recover sensitivity to ferroptosis in certain cellular models. Here, we discovered that co-treatment with the metabolically stable ferroptosis inducer imidazole ketone erastin (IKE) and the oxidized form of vitamin C, dehydroascorbic acid (DHAA), is a powerful therapy that induces ferroptosis in tumor cells previously resistant to IKE-induced ferroptosis. We determined that DHAA and IKE + DHAA delocalize and deplete GPX4 in tumor cells, specifically inducing lipid droplet peroxidation, which leads to ferroptosis. Moreover, in vivo, IKE + DHAA has high efficacy with regard to the eradication of highly aggressive tumors such as glioblastomas. Thus, the use of IKE + DHAA could be an effective and safe therapy for the eradication of difficult-to-treat cancers.
Topics: Humans; Ferroptosis; Dehydroascorbic Acid; Lipid Droplets; Neoplasms; Cell Death; Lipid Peroxidation
PubMed: 37752118
DOI: 10.1038/s41419-023-06153-9 -
Scientific Reports Sep 2023To explore potential metabolomics biomarkers in predicting post-herpetic neuralgia (PHN) induced by herpes zoster (HZ). A total of 90 eligible patients were...
To explore potential metabolomics biomarkers in predicting post-herpetic neuralgia (PHN) induced by herpes zoster (HZ). A total of 90 eligible patients were prospectively enrolled and assigned into an acute pain (ACP) group and a PHN group. Serum samples were collected before clinical intervention to perform metabolomics profiling analyses using gas chromatography mass spectrometry (GC-MS). Key metabolites were identified using partial least squares discriminant analysis (PLS-DA). A binary logistic regression was used to build a combined biomarker model to predict PHN from ACP. The discriminating efficiency of the combined biomarker model was investigated and validated by internal validation. Six metabolites were identified as the key metabolites related to PHN. All these metabolites (N-Acetyl-5-hydroxytryptaMine, glucose, dehydroascorbic acid, isopropyl-beta-D-thiogalactopyranoside, 1,5-anhydro-D-sorbitol, and glutamic acid) were found elevated in the PHN group. Pathway analyses showed that glucose-alanine cycle, tryptophan metabolism, tyrosine metabolism, lactose degradation, malate-aspartate shuttle were top five metabolic pathways evolved in PHN. The AUC was 0.85 (95% CI 0.76-0.93) for the combined biomarker model, and was 0.91 (95% CI 0.84-1.00) for the internal validation data set to predict PHN. Metabolomics analyses of key metabolites could be used to predict PHN induced by HZ.
Topics: Humans; Neuralgia, Postherpetic; Chickenpox; Varicella Zoster Virus Infection; Metabolomics; Herpes Zoster; Acute Pain; Glucose
PubMed: 37697028
DOI: 10.1038/s41598-023-42363-z -
Food Chemistry Jan 2024Glucosinolates (GLSs) are secondary plant metabolites with health-promoting effects found in Brassica vegetables. Recently, next to non-enzymatic degradation yielding...
Glucosinolates (GLSs) are secondary plant metabolites with health-promoting effects found in Brassica vegetables. Recently, next to non-enzymatic degradation yielding nitriles, 4-(methylthio)butyl GLS (4MTB-GLS) was shown to undergo side chain oxidation during thermal treatment, forming 4-(methylsulfinyl)butyl GLS (4MSOB-GLS). Here, we investigated natural plant components and artificial analogs on their capability of altering the thermal reactivity of 4MTB-GLS in vegetable broths and model systems using buffers. Addition of ascorbic acid and dehydroascorbic acid caused varying effects: in broth samples, it increased nitrile formation, while in buffer, 4MSOB-GLS was formed. In further experiments, the antioxidant compounds quercetin and Trolox triggered the side chain oxidation of 4MTB-GLS, while HS terminated its degradation. A synergistic effect of ascorbic acid and Fe was observed, degrading 98% of 4MTB-GLS to the nitrile after 60 min of boiling. Deepening the understanding of factors that influence the non-enzymatic degradation of GLSs will help to preserve their health-promoting effects.
Topics: Vegetables; Brassica; Glucosinolates; Oxidation-Reduction; Ascorbic Acid; Nitriles
PubMed: 37595380
DOI: 10.1016/j.foodchem.2023.137108 -
Nutrients Aug 2023The influence of the diet and nutritional status of milk donors on the nutritional composition of donor human milk (DHM) is unknown. The present study aimed to determine...
The influence of the diet and nutritional status of milk donors on the nutritional composition of donor human milk (DHM) is unknown. The present study aimed to determine the nutritional profile of DHM and the associations between donors' dietary intake and nutritional status and the micronutrient and lipid composition in DHM. For this purpose, 113 donors completed a food frequency questionnaire, provided a five-day weighed dietary record, and collected milk for five consecutive days. Nutrient determinations in donors' erythrocytes, plasma, urine, and milk were performed. Multiple linear regressions were conducted for the evaluation of the associations. We highlight the following results: DHM docosahexaenoic acid (DHA) was positively associated with donors' plasma DHA content and donors' DHA intake (R 0.45, < 0.001). For every 1 g/day DHA intake, an increase of 0.38% in DHA content and 0.78% in total omega-3 content was observed in DHM (R 0.29, < 0.001). DHM saturated fatty acids were positively associated with erythrocyte dimethyl acetals, plasma stearic acid, fatty acids intake, and breastfeeding duration and negatively associated with erythrocyte margaroleic acid (R 0.34, < 0.01). DHM cholecalciferol was associated with plasma cholecalciferol levels and dairy intake (R 0.57, < 0.01). Other weaker associations were found for free thiamin, free riboflavin, pyridoxal, dehydroascorbic acid, and the lipid profile in DHM. In conclusion, the diet and nutritional status of donors influence the fatty acid profile and micronutrient content of DHM.
Topics: Female; Humans; Milk, Human; Micronutrients; Eating; Fatty Acids, Omega-3; Fatty Acids; Docosahexaenoic Acids; Nutrients; Trace Elements
PubMed: 37571421
DOI: 10.3390/nu15153486 -
ACS Applied Bio Materials Aug 2023Nitric oxide (NO) is a ubiquitous messenger molecule playing a key role in various physiological and pathological processes. However, producing a selective turn-on...
Nitric oxide (NO) is a ubiquitous messenger molecule playing a key role in various physiological and pathological processes. However, producing a selective turn-on fluorescence response to NO is a challenging task due to (a) the very short half-life of NO (typically in the range of 0.1-10 s) in the biological milieu and (b) false positive responses to reactive carbonyl species (RCS) (e.g., dehydroascorbic acid and methylglyoxal etc.) and some other reactive oxygen/nitrogen species (ROS/RNS), especially with -phenylenediamine (OPD) based fluorosensors. To avoid these limitations, NO sensors should be designed in such a way that they react spontaneously with NO to give turn-on response within the time frame of (typically in the range of 0.1-10 s) of NO and λ in the visible wavelength along with good cell permeability to achieve biocompatibility. With these views in mind, a N-nitrosation based fluorescent sensor, NDAQ, has been developed that is highly selective to NO with ∼27-fold fluorescence enhancement at λ = 542 nm with high sensitivity (LOD = 7 ± 0.4 nM) and shorter response time, eliminating the interference of other reactive species (RCS/ROS/RNS). Furthermore, all the photophysical studies with NDAQ have been performed in 98% aqueous medium at physiological pH, indicating its good stability under physiological conditions. The kinetic assay illustrates the second-order dependency with respect to NO concentration and first-order dependency with respect to NDAQ concentration. The biological studies reveal the successful application of the probe to track both endogenous and exogenous NO in living organisms.
Topics: Nitric Oxide; Reactive Oxygen Species; Nitrosation; Fluorescence; Reactive Nitrogen Species; Oxygen
PubMed: 37556766
DOI: 10.1021/acsabm.3c00362