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Heart & Lung : the Journal of Critical... 2023There is currently a need to identify metabolomic responses to acute exercise in chronic obstructive pulmonary disease (COPD).
BACKGROUND
There is currently a need to identify metabolomic responses to acute exercise in chronic obstructive pulmonary disease (COPD).
OBJECTIVE
We investigated the metabolomic, oxidative, and inflammatory responses to constant (CE) and intermittent (IE) work rate exercises in COPD.
METHODS
Sixteen males with COPD performed a symptom-limited incremental cycle exercise test (ICE). Metabolomic, oxidative, and inflammatory responses to CE and IE (based on the performance of ICE) were analyzed in the plasma.
RESULTS
Fructose-6-phosphate, 3-phosphoglyceric acid, l-carnitine, and acylcarnitines levels were significantly decreased, whereas alpha-ketoglutaric, malic, 2-hydroxybutyric, and 3-hydroxybutyric acids were increased, after CE and IE (p<0.05). Increases in citric, isocitric, and lactic acids, as well as decreases in pyruvic and oxalic acids, were only present with IE (p<0.05). Isoleucine was decreased after both exercises (p<0.05). We observed an increase in inosine-5'-diphosphate, uric acid, ascorbic acid, and pantothenic acid, as well as a decrease in 5-hydroxymethyluridine, threonic acid, and dehydroascorbic acid, after IE (p<0.05). Catalase, reduced glutathione, and total antioxidant status difference values for both exercises were similar (p>0.05). The change in glutathione peroxidase (GPx) with CE was more significant than that with IE (p = 0.004). The superoxide dismutase change was greater with IE than with CE (p = 0.015). There were no significant changes in inflammatory markers after exercise (p>0.05).
CONCLUSION
CE and IE cause isoleucine, l-carnitine, and acylcarnitine levels to decrease, whereas ketone bodies were increased, thus indicating the energy metabolism shift from carbohydrates to amino acid utilization and lipid metabolism in COPD. Compared with CE, IE produces significant changes in more metabolomics in terms of carbohydrates, lipids, amino acids, nucleotides, and vitamins. Acute CE and IE alter circulating GPx levels in COPD.
Topics: Male; Humans; Isoleucine; Exercise; Carnitine; Pulmonary Disease, Chronic Obstructive; Oxidative Stress; Carbohydrates
PubMed: 36724589
DOI: 10.1016/j.hrtlng.2023.01.011 -
Free Radical Biology & Medicine Sep 2019Ascorbic acid (vitamin C) plays a significant role in the prevention of oxidative stress. In this process, ascorbate is oxidized to dehydroascorbate (DHA). We have...
Ascorbic acid (vitamin C) plays a significant role in the prevention of oxidative stress. In this process, ascorbate is oxidized to dehydroascorbate (DHA). We have investigated the impact of DHA on peptide/protein intramolecular disulfide formation as well as S-glutathionylation and S-homocysteinylation. S-glutathionylation of peptides/proteins is a reversible, potential regulatory mechanism in oxidative stress. Although the exact role of protein S-homocysteinylation is unknown, it has been proposed to be of importance in pathobiological processes such as onset of cardiovascular disease. Using an in vitro model system, we demonstrate that DHA causes disulfide bond formation within the active site of recombinant human glutaredoxin (Grx-1). DHA also facilities the formation of S-glutathionylation and S-homocysteinylation of a model peptide (AcFHACAAK) as well as Grx-1. We discuss the possible mechanisms of peptide/protein S-thiolation, which can occur either via thiol exchange or a thiohemiketal intermediate. A thiohemiketal DHA-peptide adduct was detected by mass spectrometry and its location on the peptide/protein cysteinyl thiol group was unambiguously confirmed by tandem mass spectrometry. This demonstrates that peptide/protein S-thiolation mediated by DHA is not limited to thiol exchange reactions but also takes place directly via the formation of a thiohemiketal peptide intermediate. Finally, we investigated a potential reducing role of glutathione (GSH) in the presence of S-homocysteinylated peptide/protein adducts. S-homocysteinylated AcFHACAAK, human hemoglobin α-chain and Grx-1 were incubated with GSH. Both peptide and proteins were reduced, and homocysteine replaced with GS-adducts by thiol exchange, as a function of time.
Topics: Antioxidants; Catalytic Domain; Cysteine; Dehydroascorbic Acid; Dimerization; Disulfides; Glutaredoxins; Glutathione; Hemoglobins; Homocysteine; Humans; Oxidation-Reduction; Oxidative Stress; Peptides; Sulfhydryl Compounds
PubMed: 31228548
DOI: 10.1016/j.freeradbiomed.2019.06.022 -
Roczniki Panstwowego Zakladu Higieny 2021Vitamin C is one of the most important water-soluble vitamins. It is responsible for many important functions in the body, including: it has a positive effect on...
BACKGROUND
Vitamin C is one of the most important water-soluble vitamins. It is responsible for many important functions in the body, including: it has a positive effect on maintaining immunity, protects the body against free radicals, and also participates in the synthesis of hormones. Juices can be a good source of this vitamin. Most of the juices available on the market are processed products. Untreated juices, which do not contain added preservatives, sugar and are not pasteurized, constitute a smaller group on the market. Therefore, this group of juices can be a valuable product in human nutrition.
OBJECTIVE
The aim of the study was t o analyze the content of ascorbic acid (AA), dehydroascorbic acid (DHAA) and vitamin C (TAA) in non-preserved juices, depending on their type and storage time.
MATERIAL AND METHODS
The analysis of T AA, AA and DHAA content in juices was carried out in ten types of nonpreserved juices from two companies (A and B), purchased in a chain of retail outlets. The analyzed juices in company A were: sauerkraut and carrot, grapefruit, orange, apple and mandarin, while in company B: orange, apple, apple and quince, grapefruit and mandarin. In test 1, the first ten juices were analyzed, in test 2 - another ten juices after one month, in test 3 - juices from test 2 were used, and three days after opening the package and storing the juices in standard refrigeration conditions, the stability test of AA was analyzed. The AA and TAA contents were determined using the high performance liquid chromatography (HPLC) method. The DHAA content was calculated by subtracting the AA content from the TAA content.
RESULTS
The highest TAA content was found in citrus juices, i.e. grapefruit, orange and mandarin, and the lowest in sauerkraut and carrot juices and apple juice. Moreover, ascorbic acid in apple juice was characterized by the lowest durability.
CONCLUSIONS
In the production of non-preserved apple juice, consideration should be given to the natural protection of ascorbic acid by the addition of citrus or other fruit juice, vegetable juice or by using a mild technology in the production process.
Topics: Ascorbic Acid; Citrus; Fruit; Humans; Vitamins
PubMed: 34928113
DOI: 10.32394/rpzh.2021.0187 -
Toxins Apr 2023Aflatoxins (AFs) are toxic secondary metabolites produced by spp. and are found in food and feed as contaminants worldwide. Due to climate change, AFs occurrence is...
Aflatoxins (AFs) are toxic secondary metabolites produced by spp. and are found in food and feed as contaminants worldwide. Due to climate change, AFs occurrence is expected to increase also in western Europe. Therefore, to ensure food and feed safety, it is mandatory to develop green technologies for AFs reduction in contaminated matrices. With this regard, enzymatic degradation is an effective and environmentally friendly approach under mild operational conditions and with minor impact on the food and feed matrix. In this work, Ery4 laccase, acetosyringone, ascorbic acid, and dehydroascorbic acid were investigated in vitro, then applied in artificially contaminated corn for AFB reduction. AFB (0.1 µg/mL) was completely removed in vitro and reduced by 26% in corn. Several degradation products were detected in vitro by UHPLC-HRMS and likely corresponded to AFQ, epi-AFQ, AFB-diol, or AFBdialehyde, AFB, and AFM. Protein content was not altered by the enzymatic treatment, while slightly higher levels of lipid peroxidation and HO were detected. Although further studies are needed to improve AFB reduction and reduce the impact of this treatment in corn, the results of this study are promising and suggest that Ery4 laccase can be effectively applied for the reduction in AFB in corn.
Topics: Aflatoxin B1; Zea mays; Hydrogen Peroxide; Laccase; Aflatoxins
PubMed: 37235345
DOI: 10.3390/toxins15050310 -
Small (Weinheim An Der Bergstrasse,... Jan 2023The acquired resistance to Osimertinib (AZD9291) greatly limits the clinical benefit of patients with non-small cell lung cancer (NSCLC), whereas AZD9291-resistant...
The acquired resistance to Osimertinib (AZD9291) greatly limits the clinical benefit of patients with non-small cell lung cancer (NSCLC), whereas AZD9291-resistant NSCLCs are prone to metastasis. It's challenging to overcome AZD9291 resistance and suppress metastasis of NSCLC simultaneously. Here, a nanocatalytic sensitizer (VF/S/A@CaP) is proposed to deliver Vitamin c (Vc)-Fe(II), si-OTUB2, ASO-MALAT1, resulting in efficient inhibition of tumor growth and metastasis of NSCLC by synergizing with AHP-DRI-12, an anti-hematogenous metastasis inhibitor by blocking the amyloid precursor protein (APP)/death receptor 6 (DR6) interaction designed by our lab. Fe released from Vc-Fe(II) generates cytotoxic hydroxyl radicals (•OH) through Fenton reaction. Subsequently, glutathione peroxidase 4 (GPX4) is consumed to sensitize AZD9291-resistant NSCLCs with high mesenchymal state to ferroptosis due to the glutathione (GSH) depletion caused by Vc/dehydroascorbic acid (DHA) conversion. By screening NSCLC patients' samples, metastasis-related targets (OTUB2, LncRNA MALAT1) are confirmed. Accordingly, the dual-target knockdown plus AHP-DRI-12 significantly suppresses the metastasis of AZD9291-resistant NSCLC. Such modality leads to 91.39% tumor inhibition rate in patient-derived xenograft (PDX) models. Collectively, this study highlights the vulnerability to ferroptosis of AZD9291-resistant tumors and confirms the potential of this nanocatalytic-medicine-based modality to overcome critical AZD9291 resistance and inhibit metastasis of NSCLC simultaneously.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Ferroptosis; RNA, Long Noncoding; ErbB Receptors; Drug Resistance, Neoplasm; Ferrous Compounds; Cell Line, Tumor
PubMed: 36420659
DOI: 10.1002/smll.202204133 -
Foods (Basel, Switzerland) Dec 2022The citrus juice industry produces a large amount of fiber-rich waste and other bioactive compounds of great interest for their potential health benefits. This study...
The citrus juice industry produces a large amount of fiber-rich waste and other bioactive compounds of great interest for their potential health benefits. This study focuses on the valorization of the co-product resulting from the extraction of orange juice to offer it as a versatile, healthy, high-quality, and stable natural food ingredient in powder form. To this end, the vitamin C (VC) content (ascorbic and dehydroascorbic acid, AA and DHAA), major flavonoids (hesperidin and narirutin, HES and NAT), and techno-functional properties (angle of repose, AoR; hygroscopicity and wettability; density and porosity; mean particle size, MPS; water retention capacity, WRC; oil holding capacity, ORC; emulsifying and foaming capacity, EC and FC; and emulsion and foam stability, ES and FS) have been characterized. In addition, considering that dehydrated foods with high sugar content require the incorporation of high molecular weight biopolymers for their physical stabilization, the influence of starch modified with octenyl succinic acid (OSA) and gum Arabic (GA) on these properties has been studied. The results obtained confirm the high quality of this co-product to be offered as a powdered food ingredient with nutraceutical potential. The addition of the studied biopolymers is recommended as it does not modify the flowability of the powder and favors both the encapsulation of the bioactive compounds, especially in the presence of GA, and the rehydration capacity.
PubMed: 36613313
DOI: 10.3390/foods12010097 -
Nutrients Dec 2020Vitamin C is implicated in various bodily functions due to its unique properties in redox homeostasis. Moreover, vitamin C also plays a great role in restoring the... (Review)
Review
Vitamin C is implicated in various bodily functions due to its unique properties in redox homeostasis. Moreover, vitamin C also plays a great role in restoring the activity of 2-oxoglutarate and Fe dependent dioxygenases (2-OGDD), which are involved in active DNA demethylation (TET proteins), the demethylation of histones, and hypoxia processes. Therefore, vitamin C may be engaged in the regulation of gene expression or in a hypoxic state. Hence, vitamin C has acquired great interest for its plausible effects on cancer treatment. Since its conceptualization, the role of vitamin C in cancer therapy has been a controversial and disputed issue. Vitamin C is transferred to the cells with sodium dependent transporters (SVCTs) and glucose transporters (GLUT). However, it is unknown whether the impaired function of these transporters may lead to carcinogenesis and tumor progression. Notably, previous studies have identified SVCTs' polymorphisms or their altered expression in some types of cancer. This review discusses the potential effects of vitamin C and the impaired SVCT function in cancers. The variations in vitamin C transporter genes may regulate the active transport of vitamin C, and therefore have an impact on cancer risk, but further studies are needed to thoroughly elucidate their involvement in cancer biology.
Topics: Ascorbic Acid; Basic Helix-Loop-Helix Transcription Factors; Brain Neoplasms; Breast Neoplasms; Carcinogenesis; DNA Methylation; DNA-Binding Proteins; Dehydroascorbic Acid; Dioxygenases; Epigenesis, Genetic; Female; Glioma; Glucose Transport Proteins, Facilitative; Hematologic Neoplasms; Homeostasis; Humans; Hypoxia-Inducible Factor 1; Ketoglutaric Acids; Male; Melanoma; Mixed Function Oxygenases; Neoplasms; Oxidation-Reduction; Polymorphism, Genetic; Prostatic Neoplasms; Proto-Oncogene Proteins; Sodium-Coupled Vitamin C Transporters; Vitamins
PubMed: 33352824
DOI: 10.3390/nu12123869 -
Nutrition and Cancer 2021Efforts to develop effective drugs targeting PI3K and KRAS signaling pathways in -mutant colorectal cancer stem cells (CRCSCs) remain challenging. Finding safe compounds...
The Safe Soluble Compound Dehydroascorbic Acid Inhibits Various Upstream and Downstream Effectors of PI3K and KRAS Signaling Pathways in Undruggable -Mutant Colorectal Cancer Stem-Like Cells.
Efforts to develop effective drugs targeting PI3K and KRAS signaling pathways in -mutant colorectal cancer stem cells (CRCSCs) remain challenging. Finding safe compounds that can easily enter CRCSCs with the ability to target metastasis-driver gene and pluripotency network genes as key upstream and downstream effectors of both PI3K and KRAS signaling pathways may provide promising results. -mutant CRCSCs display high expression of glucose transporters (GLUTs) on their cell membrane and a glycolytic phenotype providing an opportunity to deliver antiglycolytic compounds into these cells via the GLUTs. CRC patients with low levels of vitamin C in their plasma show a shorter survival suggesting the ability of this vitamin at the physiologic levels for caspase-3 activation and apoptosis in CRCSCs. Vitamin C in an oxidized form (L-dehydroascorbic acid; L-DHA) with antiglycolytic activity can be taken up into CRC cells via the GLUTs. This may provide selective toxicity on CRCSCs and affect and stemness markers genes expression in these cells. To this end, we treated /-mutant LS174T cells with high glycolytic activity as an attractive model for CRCSCs with L-DHA equal to the pharmacological levels of vitamin C in human plasma, after which cell numbers, metabolic activity, proliferation-rate, and pluripotency network genes expression, caspase-3 activity with apoptosis were evaluated. 48 h post-treatment with 100- to 1000 µM L-DHA, cell numbers were decreased and measured to be 70-47% control. L-DHA with selective toxicity on LS174T cells diminished metabolic activity and cell proliferation-rate to 1.4-0.8 (Control OD = 1.5) and 92-54.5% respectively with no toxicity on PBMCs. L-DHA decreased , , -2 and expression to 45%, 85%, 45% and 48% control respectively followed by caspase-3 reactivation by 2.5 to 4.9-fold increases and induction of apoptosis ranging from 0.5% to 58.3% for 100- to 1000 µM L-DHA. According to our data, CRC stem-like cells were highly sensitive to L-DHA in . L-DHA selectively targeted LS174T cells and successfully reactivated caspase-3 and apoptosis in these cells. , stemness marker genes and metabolic activity appear to be promising targets of L-DHA. Our results may provide a new therapeutic approach to target selectively GLUT-overexpressing -mutant CRCSCs using L-DHA with no toxicity on normal cells.
Topics: Cell Line, Tumor; Class I Phosphatidylinositol 3-Kinases; Colorectal Neoplasms; Dehydroascorbic Acid; Humans; Mutation; Neoplastic Stem Cells; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins p21(ras); Signal Transduction
PubMed: 33283545
DOI: 10.1080/01635581.2020.1856387 -
Journal of Cellular Physiology Dec 2020Oxidative stress and inflammation are crucial factors that increase with age. In the progression of multiple age-related diseases, antioxidants and bioactive compounds...
Oxidative stress and inflammation are crucial factors that increase with age. In the progression of multiple age-related diseases, antioxidants and bioactive compounds have been recognized as useful antiaging agents. Oxidized or reduced vitamin C exerts different actions on tissues and has different metabolism and uptake. In this study, we analyzed the antiaging effect of vitamin C, both oxidized and reduced forms, in renal aging using laser microdissection, quantitative reverse-transcription polymerase chain reaction, and immunohistochemical analyses. In the kidneys of old SAM mice (10 months of age), a model of accelerated senescence, vitamin C, especially in the oxidized form (dehydroascorbic acid [DHA]) improves renal histology and function. Serum creatinine levels and microalbuminuria also decrease after treatment with a decline in azotemia. In addition, sodium-vitamin C cotransporter isoform 1 levels, which were increased during aging, are normalized. In contrast, the pattern of glucose transporter 1 expression is not affected by aging or vitamin C treatment. We conclude that oxidized and reduced vitamin C are potent antiaging therapies and that DHA reverses the kidney damage observed in senescence-accelerated prone mouse 8 to a greater degree.
Topics: Aging; Animals; Ascorbic Acid; Dehydroascorbic Acid; Gene Expression Regulation; Glucose Transporter Type 1; Humans; Inflammation; Kidney; Mice; Oxidative Stress; Sodium-Coupled Vitamin C Transporters
PubMed: 32437012
DOI: 10.1002/jcp.29791 -
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