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Frontiers in Neuroscience 2023Different studies have established the fundamental role of vitamin C in proliferation, differentiation, and neurogenesis in embryonic and adult brains, as well as in... (Review)
Review
Different studies have established the fundamental role of vitamin C in proliferation, differentiation, and neurogenesis in embryonic and adult brains, as well as in cell models. To fulfill these functions, the cells of the nervous system regulate the expression and sorting of sodium-dependent vitamin C transporter 2 (SVCT2), as well as the recycling of vitamin C between ascorbic acid (AA) and dehydroascorbic acid (DHA) via a bystander effect. SVCT2 is a transporter preferentially expressed in neurons and in neural precursor cells. In developmental stages, it is concentrated in the apical region of the radial glia, and in adult life, it is expressed preferentially in motor neurons of the cerebral cortex, starting on postnatal day 1. In neurogenic niches, SVCT2 is preferentially expressed in precursors with intermediate proliferation, where a scorbutic condition reduces neuronal differentiation. Vitamin C is a potent epigenetic regulator in stem cells; thus, it can induce the demethylation of DNA and histone H3K27m3 in the promoter region of genes involved in neurogenesis and differentiation, an effect mediated by Tet1 and Jmjd3 demethylases, respectively. In parallel, it has been shown that vitamin C induces the expression of stem cell-specific microRNA, including the Dlk1-Dio3 imprinting region and miR-143, which promotes stem cell self-renewal and suppresses expression of the methyltransferase gene Dnmt3a. The epigenetic action of vitamin C has also been evaluated during gene reprogramming of human fibroblasts to induced pluripotent cells, where it has been shown that vitamin C substantially improves the efficiency and quality of reprogrammed cells. Thus, for a proper effect of vitamin C on neurogenesis and differentiation, its function as an enzymatic cofactor, modulator of gene expression and antioxidant is essential, as is proper recycling from DHA to AA by various supporting cells in the CNS.
PubMed: 37424994
DOI: 10.3389/fnins.2023.1155758 -
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 -
Frontiers in Microbiology 2023The production of pyocyanin by increases its virulence, fitness and biofilm formation. Pyocyanin is also a redox molecule and we hypothesize that ascorbic acid being an...
The production of pyocyanin by increases its virulence, fitness and biofilm formation. Pyocyanin is also a redox molecule and we hypothesize that ascorbic acid being an antioxidant will interact with pyocyanin. The main objective of this study was to investigate the potential interaction of ascorbic acid with pyocyanin, and also to investigate the impact of ascorbic acid in combination with Furanone-30 on quorum sensing and biofilm formation of . When incubated with ascorbic acid, hyperchromic and hypsochromic shifts in pyocyanin absorbance peaks at 385 nm and 695 nm were observed. In the presence of dehydroascorbic acid and citric acid, these shifts were absent, indicating that the intrinsic antioxidant property of ascorbic acid was probably essential in binding to pyocyanin. NMR spectroscopy showed shifts in H NMR pyocyanin peaks between 8.2 to 5.8 ppm when incubated in the presence of ascorbic acid. Density Functional Theory (DFT) supported potential interactions between the -CHOH or -OH moieties of ascorbic acid with the -C=O moiety of pyocyanin. The pyocyanin-ascorbic acid complex impaired pyocyanin binding to DNA. Ascorbic acid combined with furanone-30 elevated quorum-sensing inhibition in , which was directly associated with significantly reduced virulence, adhesion, aggregation and biofilm formation and enhanced antibiotic-mediated bacterial killing. This study demonstrated that the antioxidant ascorbic acid directly binds to pyocyanin, modulates its structure and results in disruption of biofilm formation and associated tolerance to antibiotics.
PubMed: 37520362
DOI: 10.3389/fmicb.2023.1166607 -
Stem Cell Research & Therapy Jan 2024After myocardial infarction, the lost myocardium is replaced by fibrotic tissue, eventually progressively leading to myocardial dysfunction. Direct reprogramming of...
BACKGROUND
After myocardial infarction, the lost myocardium is replaced by fibrotic tissue, eventually progressively leading to myocardial dysfunction. Direct reprogramming of fibroblasts into cardiomyocytes via the forced overexpression of cardiac transcription factors Gata4, Mef2c, and Tbx5 (GMT) offers a promising strategy for cardiac repair. The limited reprogramming efficiency of this approach, however, remains a significant challenge.
METHODS
We screened seven factors capable of improving direct cardiac reprogramming of both mice and human fibroblasts by evaluating small molecules known to be involved in cardiomyocyte differentiation or promoting human-induced pluripotent stem cell reprogramming.
RESULTS
We found that vitamin C (VitC) significantly increased cardiac reprogramming efficiency when added to GMT-overexpressing fibroblasts from human and mice in 2D and 3D model. We observed a significant increase in reactive oxygen species (ROS) generation in human and mice fibroblasts upon Doxy induction, and ROS generation was subsequently reduced upon VitC treatment, associated with increased reprogramming efficiency. However, upon treatment with dehydroascorbic acid, a structural analog of VitC but lacking antioxidant properties, no difference in reprogramming efficiency was observed, suggesting that the effect of VitC in enhancing cardiac reprogramming is partly dependent of its antioxidant properties.
CONCLUSIONS
Our findings demonstrate that VitC supplementation significantly enhances the efficiency of cardiac reprogramming, partially by suppressing ROS production in the presence of GMT.
Topics: Humans; Mice; Animals; Reactive Oxygen Species; Ascorbic Acid; Antioxidants; Cellular Reprogramming; T-Box Domain Proteins; MEF2 Transcription Factors; Myocytes, Cardiac; Vitamins; Fibroblasts
PubMed: 38229180
DOI: 10.1186/s13287-023-03615-x -
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 -
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 -
Journal of Food Protection May 2024Chlorine is commonly used by the fresh produce industry to sanitize water and minimize pathogen cross-contamination during handling. The pH of chlorinated water is often...
Chlorine is commonly used by the fresh produce industry to sanitize water and minimize pathogen cross-contamination during handling. The pH of chlorinated water is often reduced to values of pH 6-7, most commonly with citric acid to stabilize the active antimicrobial, hypochlorous acid (a form of free chlorine). Previous studies have demonstrated that citric acid reacts with chlorine to form trichloromethane, a major chlorine by-product in water and a potential human carcinogen. However, it is unclear if other pH control agents could be used in the place of citric acid to minimize the formation of trichloromethane. The objective of the present study was to determine the reactivity of organic and inorganic pH control agents, with chlorine, to generate trichloromethane. Free chlorine (∼100 mg/L) was mixed with 10 mM of each of twelve organic acids and two inorganic pH control agents (i.e., sodium acid sulfate and phosphoric acid) to effect a pH level of 6.5. Free chlorine and trichloromethane levels were measured over 3 h at 3 and 22°C. Results demonstrated that ascorbic acid, dehydroascorbic acid, citric acid, and malic acid rapidly depleted free chlorine concentrations at both 22°C and 3°C, while tartaric acid and lactic acid decreased chlorine concentrations more slowly. Other pH control agents did not significantly reduce free chlorine either at 22 or 3°C. Citric acid led to the generation of significantly higher concentrations of trichloromethane than did other acids. Chloroacetone was also found in chlorinated water in the presence of citric acid and ascorbic acid. Taking buffering capacity and pKa values into account, phosphoric acid and some organic acids may be used to replace citric acid as pH control agents in chlorinated water for washing fresh produce, to stabilize free chlorine level and reduce the generation of trichloromethane.
PubMed: 38734411
DOI: 10.1016/j.jfp.2024.100296 -
Scientific Reports Dec 2023Low temperature is one of the major constraints on agricultural productivity worldwide and is likely to further increase. Several adaptations and mitigation strategies...
Low temperature is one of the major constraints on agricultural productivity worldwide and is likely to further increase. Several adaptations and mitigation strategies are required to cope with low-temperature stress. Uniconazole (S3307) could play a significant role in the alleviation of abiotic stress in plants. In this study, the effects of S3307 on the reactive oxygen species (ROS) and antioxidant metabolism were studied in the leaves of mung bean [Vigna radiata (L.) Wilczek]. The experimental results showed that the low-temperature induced accumulation of superoxide anion (O) production rate, and malonaldehyde (MDA) contents. Increased proline content and enzymatic antioxidants, including superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), were found to alleviate oxidative damage under low temperatures. While, S3307 could reduce O production rate and MDA contents and increase the activities of SOD, POD, and CAT, slowed the decrease in ascorbic acid (AsA), dehydroascorbic acid (DHA), glutathione (GSH), and oxidized glutathione (GSSG), and promoted increase in soluble sugars (SS), soluble proteins (SP), and proline (Pro) content under low-temperature. At the same time, low temperature leads to lower 100 grain weight and number of grains per plant, which eventually causes yield reduction decreased. Foliar spraying of S3307 could alleviate the yield loss caused by low temperature, and the increase of S3307 treatment was 5.1%-12.5% and 6.3%-32.9% for the two varieties, respectively, compared with CK. In summary, exogenous S3307 pretreatment enhances plant tolerance to low-temperature by improving the antioxidant enzyme activities, increased non-enzymatic antioxidants content, and decreased O production rate and MDA contents and inducing alterations in endogenous S3307, and reduce the decrease in mung bean yield.
Topics: Antioxidants; Vigna; Temperature; Fabaceae; Superoxide Dismutase; Peroxidases; Glutathione; Peroxidase; Proline
PubMed: 38102232
DOI: 10.1038/s41598-023-49652-7 -
Foods (Basel, Switzerland) Jan 2024Salmorejo, a Mediterranean tomato-oil puree, is considered a dietary source of antioxidant vitamins C and E and carotenoids lycopene and β-carotene, the latter endowed...
Salmorejo, a Mediterranean tomato-oil puree, is considered a dietary source of antioxidant vitamins C and E and carotenoids lycopene and β-carotene, the latter endowed with provitamin A activity. However, these antioxidants can be degraded in oxidation reactions catalysed or not by enzymes during pasteurisation and storage treatments used to stabilise the salmorejo before consumption. Due to its better penetration, the use of dielectric heating by radiofrequency (RF) may improve results of pasteurisation in this product. The objective was to assess the effects of pasteurisation temperature (70-100 °C, at 5 °C intervals) and storage time (0-5 months, at one-month intervals) on levels of ascorbic acid, α-tocopherol and carotenoids and antioxidant capacity (AC) in salmorejo pasteurised (over 10 s) by conventional (CH) or RF continuous heating. Two successive experiments were conducted to select an adequate pasteurisation temperature for use in the shelf-life study. Pasteurisation upon tested conditions allows a good retention of salmorejo antioxidants. Either CH or RF pasteurisers can be used with similar results. Vitamin C (L-ascorbic + dehydroascorbic acids) was more abundant (15-19 mg 100 g) than carotenoids (0.9-2.6 mg 100 g) (all- + lycopene and β-carotene) and α-tocopherol (0.8-1.2 mg 100 g) in the pasteurised product. Using excessively low temperatures (70 °C) resulted in partial losses of the three antioxidants, possibly due to oxidase residual activities. Intensifying thermal treatment improved this issue with minor losses of the thermolabile vitamin C and increased carotenoid content. Using a suitable temperature (80 °C) did not prevent most vitamin C from being degraded by the first month, while α-tocopherol, and, to a lesser extent, carotenoids, showed good retention levels during shelf life under refrigeration. Vitamins C and E and carotenoids, either by degradation, regeneration or releasing, likely contribute to the AC in salmorejo. Phenolic antioxidant response, radical-scavenging activities and redox potential values confirmed this finding. The pasteurised-chilled salmorejo shows good antioxidant properties with potential health implications, a positive nutritional aspect for consumers of this tomato-oil homogenate. The losses of antioxidants and AC due to pasteurization would be of little relevance compared to the losses accumulated during shelf life.
PubMed: 38275716
DOI: 10.3390/foods13020349