[Biosynthesis of water-soluble vitamins].

Vitamins are a class of organic substances essential for maintaining the normal physiological function of organisms. Most vitamins cannot be synthesized by the human body, and a small number of vitamins can only be synthesized in a limited manner, which cannot meet the body needs. Therefore, people need to take food or drugs containing vitamins to meet the body needs. Nowadays, vitamins are widely used in medicine, food or feed additives, cosmetics and other industries, and the demand for vitamins is growing. Vitamins are mainly produced by chemical synthesis and biosynthesis. Compared with chemical synthesis, biosynthesis of vitamins is praised for the environmental friendliness, high safety, and low costs. Therefore, it is of great practical significance to study the biosynthesis methods of vitamins. This paper reviews the research progress in the methods and summarizes the research results in the biosynthesis of water-soluble vitamins (B vitamins and vitamin C) in recent years and then makes an outlook on the future development in this field.

Changes in fruit quality properties and phytochemical substances of kiwifruit (Actinidia deliciosa) grown in different agro-ecological conditions during cold storage.

BACKGROUND: The changes in the physical structures of the products are the first things that consumers pay attention to. Therefore, it is essential and significant importance to take measures to improve the storage conditions of products and to minimize quality losses. The main objective of the study was to evaluate the effects of agro-ecological conditions on bioactive compounds and fruit quality of kiwifruit during cold storage. The 'Hayward' kiwifruit cultivar grown in Ordu, Giresun, Samsun, Rize, and Yalova provinces of Türkiye were kept at 0 ± 0.5 °C and relative humidity of 90 ± 5% for 150 d. RESULTS: The kiwifruit obtained from the provinces of Yalova, Ordu, and Giresun experienced the least weight loss during cold storage. Kiwifruit from Samsun and Yalova provinces had the lowest fruit firmness, while those from Giresun had the highest on 150th d. The changes were observed in the skin and flesh colors of the kiwifruit belonging to all cultivation areas. The amount of vitamin C increased throughout the study in all ecological conditions, but the Yalova province's kiwifruit was found to have the highest levels. Additionally, in all ecologies, kiwifruit showed an increase in antioxidant activity, total phenolics, and total flavonoids, all known to have beneficial effects on human health. The total antioxidant activity and total phenolics were highest in the kiwifruit of Yalova province, but the total flavonoids were found in the kiwifruit of Rize and Ordu provinces. CONCLUSION: The study's results revealed that kiwifruit's bioactive compounds and quality parameters may vary depending on the cultivation area. Additionally, it can be stated that Yalova province kiwifruit experiences the least amount of postharvest quality losses.

Intra-canopy LED lighting outperformed top LED lighting in improving tomato yield and expression of the genes responsible for lycopene, phytoene and vitamin C synthesis.

Greenhouses located at high latitudes and in cloudy areas often experience a low quality and quantity of light, especially during autumn and winter. This low daily light integral (DLI) reduces production rate, quality, and nutritional value of many crops. This study was conducted on Sakhiya RZ F1 tomato plants to evaluate the impact of LED lights on the growth and nutritional value of tomatoes in a greenhouse with low daily light due to cloudy weather. The treatments included LED growth lights in three modes: top lighting, intra-canopy lighting, and combined top and intra-canopy lighting. The results showed that although the combined top and intra-canopy lighting reached the maximum increase in tomato yield, exposure to intra-canopy LED lighting alone outperformed in tomato fruit yield increase (28.46%) than exposure to top LED lighting alone (12.12%) when compared to no supplemental lighting during the entire production year. Intra-canopy exposure demonstrated the highest increase in tomato lycopene (31.3%), while top and intra-canopy lighting exhibited the highest increase in vitamin C content (123.4%) compared to the control. The LED light treatment also had a very positive effect on the expression of genes responsible for metabolic cycles, including Psy1, LCY-ß, and VTC2 genes, which had collinearity with the increase in tomato fruit production.

Interdomain-linkers control conformational transitions in the SLC23 elevator transporter UraA.

Uptake of nucleobases and ascorbate is an essential process in all living organisms mediated by SLC23 transport proteins. These transmembrane carriers operate via the elevator alternating-access mechanism, and are composed of two rigid domains whose relative motion drives transport. The lack of large conformational changes within these domains suggests that the interdomain-linkers act as flexible tethers. Here, we show that interdomain-linkers are not mere tethers, but have a key regulatory role in dictating the conformational space of the transporter and defining the rotation axis of the mobile transport domain. By resolving a wide inward-open conformation of the SLC23 elevator transporter UraA and combining biochemical studies using a synthetic nanobody as conformational probe with hydrogen-deuterium exchange mass spectrometry, we demonstrate that interdomain-linkers control the function of transport proteins by influencing substrate affinity and transport rate. These findings open the possibility to allosterically modulate the activity of elevator proteins by targeting their linkers.

Impact of Dropping on Postharvest Physiology of Tomato Fruits Harvested at Green and Red Ripeness Stages.

Dropping during transportation is a critical issue for tomato fruits, as it triggers ethylene production and affects quality parameters, leading to lower quality and a reduced storage life. Thus, this study was conducted to assess the physiological alterations in tomato fruits subjected to dropping. This study involved tomatoes harvested at green and red stages, subjected to the following five dropping treatments: 0 cm, 10 cm, 30 cm, 50 cm, and 100 cm. The results revealed that dropping from 100 cm induced the highest ethylene production, particularly in green fruits, where production began within one hour and peaked within 48 h. Red fruits exhibited a dose-dependent response to mechanical stress, with a notable decrease in ethylene production starting from the second week post-dropping, suggesting a regulatory mechanism. CO2 production peaked at 350.1 µL g-1 h-1 in green fruits and 338.2 µL g-1 h-1 in red fruits one day after dropping from 100 cm. Dropping also significantly influenced fruit color, firmness, electrolyte leakage, and vitamin C content. Principal component analysis (PCA) revealed distinct changes in metabolite profiles, with methionine and ACC (1-aminocyclopropane-1-carboxylate), key ethylene precursors, increasing in response to dropping, particularly in red fruits. These findings underscore the critical role of mechanical stress in modulating fruit physiology, with implications for post-harvest handling practices aimed at enhancing fruit quality and shelf life.

Balanced Duality: H2O2-Based Therapy in Cancer and Its Protective Effects on Non-Malignant Tissues.

Conventional cancer therapy strategies, although centered around killing tumor cells, often lead to severe side effects on surrounding normal tissues, thus compromising the chronic quality of life in cancer survivors. Hydrogen peroxide (H2O2) is a secondary signaling molecule that has an array of functions in both tumor and normal cells, including the promotion of cell survival pathways and immune cell modulation in the tumor microenvironment. H2O2 is a reactive oxygen species (ROS) crucial in cellular homeostasis and signaling (at concentrations maintained under nM levels), with increased steady-state levels in tumors relative to their normal tissue counterparts. Increased steady-state levels of H2O2 in tumor cells, make them vulnerable to oxidative stress and ultimately, cell death. Recently, H2O2-producing therapies-namely, pharmacological ascorbate and superoxide dismutase mimetics-have emerged as compelling complementary treatment strategies in cancer. Both pharmacological ascorbate and superoxide dismutase mimetics can generate excess H2O2 to overwhelm the impaired H2O2 removal capacity of cancer cells. This review presents an overview of H2O2 metabolism in the physiological and malignant states, in addition to discussing the anti-tumor and normal tissue-sparing mechanism(s) of, and clinical evidence for, two H2O2-based therapies, pharmacological ascorbate and superoxide dismutase mimetics.

Phosphorus-induced restructuring of the ascorbate-glutathione cycle and lignin biosynthesis alleviates manganese toxicity in peach roots.

Manganese (Mn) is indispensable for plant growth, but its excessive uptake in acidic soils leads to toxicity, hampering food safety. Phosphorus (P) application is known to mitigate Mn toxicity, yet the underlying molecular mechanism remains elusive. Here, we conducted physiological and transcriptomic analyses of peach roots response to P supply under Mn toxicity. Manganese treatment disrupted root architecture and caused ultrastructural damage due to oxidative injury. Notably, P application ameliorated the detrimental effects and improved the damaged roots by preventing the shrinkage of cortical cells, epidermis and endodermis, as well as reducing the accumulation of reactive oxygen species (ROS). Transcriptomic analysis revealed the differentially expressed genes enriched in phenylpropanoid biosynthesis, cysteine, methionine and glutathione metabolism under Mn and P treatments. Phosphorus application upregulated the transcripts and activities of core enzymes crucial for lignin biosynthesis, enhancing cell wall integrity. Furthermore, P treatment activated ascorbate-glutathione cycle, augmenting ROS detoxification. Additionally, under Mn toxicity, P application downregulated Mn uptake transporter while enhancing vacuolar sequestration transporter transcripts, reducing Mn uptake and facilitating vacuolar storage. Collectively, P application prevents Mn accumulation in roots by modulating Mn transporters, bolstering lignin biosynthesis and attenuating oxidative stress, thereby improving root growth under Mn toxicity. Our findings provide novel insights into the mechanism of P-mediated alleviation of Mn stress and strategies for managing metal toxicity in peach orchards.

Dimeric transport mechanism of human vitamin C transporter SVCT1.

Vitamin C plays important roles as a cofactor in many enzymatic reactions and as an antioxidant against oxidative stress. As some mammals including humans cannot synthesize vitamin C de novo from glucose, its uptake from dietary sources is essential, and is mediated by the sodium-dependent vitamin C transporter 1 (SVCT1). Despite its physiological significance in maintaining vitamin C homeostasis, the structural basis of the substrate transport mechanism remained unclear. Here, we report the cryo-EM structures of human SVCT1 in different states at 2.5-3.5 Å resolutions. The binding manner of vitamin C together with two sodium ions reveals the counter ion-dependent substrate recognition mechanism. Furthermore, comparisons of the inward-open and occluded structures support a transport mechanism combining elevator and distinct rotational motions. Our results demonstrate the molecular mechanism of vitamin C transport with its underlying conformational cycle, potentially leading to future industrial and medical applications.

Ascorbate, plant hormones and their interactions during plant responses to biotic stress.

Plants can experience a variety of environmental stresses that significantly impact their fitness and survival. Additionally, biotic stress can harm agriculture, leading to reduced crop yields and economic losses worldwide. As a result, plants have developed defense strategies to combat potential invaders. These strategies involve regulating redox homeostasis. Several studies have documented the positive role of plant antioxidants, including Ascorbate (Asc), under biotic stress conditions. Asc is a multifaceted antioxidant that scavenges ROS, acts as a co-factor for different enzymes, regulates gene expression, and facilitates iron transport. However, little attention has been given to Asc and its transport, regulatory effects, interplay with phytohormones, and involvement in defense processes under biotic stress. Asc interacts with other components of the redox system and phytohormones to activate various defense responses that reduce the growth of plant pathogens and promote plant growth and development under biotic stress conditions. Scientific reports indicate that Asc can significantly contribute to plant resistance against biotic stress through mutual interactions with components of the redox and hormonal systems. This review focuses on the role of Asc in enhancing plant resistance against pathogens. Further research is necessary to gain a more comprehensive understanding of the molecular and cellular regulatory processes involved.

The Antioxidant Defense System of Tomato (Solanum lycopersicum L.) Varieties under Drought Stress and upon Post-Drought Rewatering.

Water shortage induces physiological, biochemical, and molecular alterations in plant leaves that play an essential role in plant adaptive response. The effects of drought and post-drought rewatering on the activity of antioxidant enzymes and levels of H2O2, phenolic compounds, ascorbic acid, and proline were studied in six local tomato (Solanum lycopersicum L.) varieties. The contents of H2O2 and ascorbic acid increased in all drought-exposed tomato plants and then decreased upon rewatering. The level of phenolic compounds also decreased in response to water shortage and then recovered upon rehydration, although the extent of this response was different in different varieties. The activities of ascorbate peroxidase (APX) and guaiacol peroxidase (POX) and the content of proline significantly increased in the drought-stressed plants and then decreased when the plants were rewatered. The activities of 8 constitutive APX isoforms and 2 constitutive POX isoforms varied upon exposure to drought and were observed after rewatering in all studied varieties. The information on the response of tomato plants to drought and subsequent rewatering is of great importance for screening and selection of drought-tolerant varieties, as well as for development of strategies for increasing plant productivity under adverse environmental conditions.

In vivo absorption and excretion in rats and in vitro digestion and fermentation by the human intestinal microbiota of 2-O-ß-D-glucopyranosyl-L-ascorbic acid from the fruits of Lycium barbarum L.

2-O-ß-D-Glucopyranosyl-L-ascorbic acid (AA-2ßG) from Lycium barbarum fruits has diverse bioactivities, yet its absorption and digestion are poorly understood. Therefore, the in vivo absorption of AA-2ßG in rats was investigated in the present study. After oral administration to SD rats, AA-2ßG was absorbed intact, reaching a peak plasma concentration of 472.32 ± 296.64 nM at 90 min, with fecal excretion peaking at 4-8 h and decreasing rapidly by 12-24 h, indicating a prolonged intestinal presence. Furthermore, the digestibility under simulated gastrointestinal conditions and the impact on the gut flora through in vitro fermentation of AA-2ßG were investigated. The results reveal that AA-2ßG resisted in in vitro simulated digestion, indicating potential interactions with the gut microbiota. The results of in vitro fermentation showed that AA-2ßG regulated the composition of the gut microbiota by promoting Oscillospiraceae, Faecalibacterium, Limosilactobacillus, and Fusicatenibacter, while inhibiting Enterococcus, Phocaeicola, Bacteroides, and Streptococcus. Furthermore, at the species level, AA-2ßG promoted the growth of Limosilactobacillus mucosae and Faecalibacterium prausnitzii, and inhibited the growth of Enterococcus. F. prausnitzii is a major producer of n-butyric acid, and the results of short-chain fatty acids also demonstrated a significant promotion of n-butyric acid. Therefore, the study on the absorption, excretion, and regulatory effects of AA-2ßG on the gut microbiota supported its potential development as a functional food additive to enhance intestinal health and prevent diseases.

Vitamin C inactivates c-Jun N-terminal kinase to stabilize heart and neural crest derivatives expressed 1 (Hand1) in regulating placentation and maintenance of pregnancy.

Vitamin C (VC) serves as a pivotal nutrient for anti-oxidation process, metabolic responses, and stem cell differentiation. However, its precise contribution to placenta development and gestation remains obscure. Here, we demonstrated that physiological levels of VC act to stabilize Hand1, a key bHLH transcription factor vital for the development trajectory of trophoblast giant cell (TGC) lineages, thereby promoting the differentiation of trophoblast stem cells into TGC. Specifically, VC administration inactivated c-Jun N-terminal kinase (JNK) signaling, which directly phosphorylates Hand1 at Ser48, triggering the proteasomal degradation of Hand1. Conversely, a loss-of-function mutation at Ser48 on Hand1 not only significantly diminished both intrinsic and VC-induced stabilization of Hand1 but also underscored the indispensability of this residue. Noteworthy, the insufficiency of VC led to severe defects in the differentiation of diverse TGC subtypes and the formation of labyrinth's vascular network in rodent placentas, resulting in failure of maintenance of pregnancy. Importantly, VC deficiency, lentiviral knockdown of JNK or overexpression of Hand1 mutants in trophectoderm substantially affected the differentiation of primary and secondary TGC in E8.5 mouse placentas. Thus, these findings uncover the significance of JNK inactivation and consequential stabilization of Hand1 as a hitherto uncharacterized mechanism controlling VC-mediated placentation and perhaps maintenance of pregnancy.

Ascorbate insufficiency disrupts glutamatergic signaling and alters electroencephalogram phenotypes in a mouse model of Alzheimer's disease.

Clinical studies have reported that increased epileptiform and subclinical epileptiform activity can be detected in many patients with an Alzheimer's disease (AD) diagnosis using electroencephalogram (EEG) and this may correlate with poorer cognition. Ascorbate may have a specific role as a neuromodulator in AD as it is released concomitantly with glutamate reuptake following excitatory neurotransmission. Insufficiency may therefore result in an exacerbated excitatory/inhibitory imbalance in neuronal signaling. Using a mouse model of AD that requires dietary ascorbate (Gulo-/-APPswe/PSEN1dE9), EEG was recorded at baseline and during 4 weeks of ascorbate depletion in young (5-month-old) and aged (20-month-old) animals. Data were scored for changes in quantity of spike trains, individual spikes, sleep-wake rhythms, sleep fragmentation, and brainwave power bands during light periods each week. We found an early increase in neuronal spike discharges with age and following ascorbate depletion in AD model mice and not controls, which did not correlate with brain amyloid load. Our data also show more sleep fragmentation with age and with ascorbate depletion. Additionally, changes in brain wave activity were observed within different vigilance states in both young and aged mice, where Gulo-/-APPswe/PSEN1dE9 mice had shifts towards higher frequency bands (alpha, beta, and gamma) and ascorbate depletion resulted in shifts towards lower frequency bands (delta and theta). Microarray data supported ascorbate insufficiency altering glutamatergic transmission through the decreased expression of glutamate related genes, however no changes in protein expression of glutamate reuptake transporters were observed. These data suggest that maintaining optimal brain ascorbate levels may support normal brain electrical activity and sleep patterns, particularly in AD patient populations where disruptions are observed.

Expression of the alfalfa gene MsMDHAR in Arabidopsis thaliana increases water stress tolerance.

The ascorbate-glutathione pathway plays an essential role in the physiology of vascular plants, particularly in their response to environmental stresses. This pathway is responsible for regulating the cellular redox state, which is critical for maintaining cell function and survival under adverse conditions. To study the involvement of the alfalfa monodehydroascorbate reductase (MsMDHAR) in water stress processes, Arabidopsis thaliana plants constitutively expressing the sequence encoding MsMDHAR were developed. Transgenic events with low and high MsMDHAR expression and ascorbate levels were selected for further analysis of drought and waterlogging tolerance. Under water stress, Arabidopsis transgenic plants generated higher biomass, produced more seeds, and had larger roots than wild type ones. This higher tolerance was associated with increased production of waxes and chlorophyll a at the basal level, greater stomatal opening and stability in regulating the relative water content and reduced H2O2 accumulation under stress conditions in transgenic plants. Overall, these results show that MsMDHAR is involved in plant tolerance to abiotic stresses. The data presented here also emphasises the potential of the MsMDHAR enzyme as a plant breeding tool to improve water stress tolerance.

Profile of key metabolites and identification of HMGCS1-DHEA pathway in porcine Sertoli cells treated by Vitamin C.

Vitamin C (Ascorbic acid, AA), as vital micro-nutrient, plays an essential role for male animal reproduction. Previously, we showed that vitamin C reprogrammed the transcriptome and proteome to change phenotypes of porcine immature Sertoli cells (iSCs). Here, we used LC-MS-based non-targeted metabolomics to further investigate the metabolic effects of vitamin C on porcine iSCs. The results identified 43 significantly differential metabolites (DMs) (16 up and 27 down) as induced by vitamin C (L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate, AA2P) treatment of porcine iSCs, which were mainly enriched in steroid related and protein related metabolic pathways. ELISA (Enzyme-Linked ImmunoSorbent Assay) showed that significantly differential metabolites of Dehydroepiandrosterone (DHEA) (involved in steroid hormone biosynthesis) and Desmosterol (involved in steroid degradation) were significantly increased, which were partially consistent with metabolomic results. Further integrative analysis of metabolomics, transcriptomics and proteomics data identified the strong correlation between the key differential metabolite of Dehydroepiandrosterone and 6 differentially expressed genes (DEGs)/proteins (DEPs) (HMGCS1, P4HA1, STON2, LOXL2, EMILIN2 and CCN3). Further experiments validated that HMGCS1 could positively regulate Dehydroepiandrosterone level. These data indicate that vitamin C could modulate the metabolism profile, and HMGCS1-DHEA could be the pathway to mediate effects exerted by vitamin C on porcine iSCs.

Molecular Pharmacology of Vitamin C and Relevance to Health and Obesity-A Narrative Review.

The role of food constituents as pharmacological agents is an important consideration in health and obesity. Vitamin C acts as a small molecule antioxidant but is also a co-factor for numerous transition metal-dependent enzymes involved in healthy weight and energy metabolism. Vitamin C cannot be manufactured by humans and is mainly obtained from the dietary intake of fresh fruit and vegetables. There is great variability between different nutritional guidelines in the recommended daily allowance of vitamin C. Vitamin C deficiency results from an inadequate intake of vitamin C-containing foods and also increased utilization by oxidative and carbonyl stress. Risk factors for vitamin C deficiency include cigarette smoking, malnutrition, obesity, type 2 diabetes mellitus, age, race, sex, social isolation, major surgery, and Western-type diets. Despite the common belief that vitamin C deficiency is rare in affluent countries, surveys of large populations and specific patient groups suggest otherwise. Patients with obesity typically consume highly processed, energy-dense foods which contain inadequate micronutrients. As obesity increases, larger amounts of oral vitamin C are required to achieve adequate plasma and tissue concentrations, as compared to persons with a healthy weight. This is important in the control of oxidative stress and the maintenance of homeostasis and organ function. In this narrative review, the dosage, absorption, distribution, excretion, and catabolism of vitamin C are reviewed, together with the latest findings on vitamin C pharmacology in patients with obesity.

Bioaccessibility and Caco-2 cell uptake of iron chlorophyllin using a biologically relevant digestion model.

Iron deficiency remains a top nutrient deficiency worldwide. Iron chlorophyllin (IC), a compound structurally analogous to heme, utilizes the protoporphyrin ring of chlorophyll to bind iron. IC has previously been shown to deliver more iron to Caco-2 cells than FeSO4, the most common form prescribed for supplementation. However, previous test conditions used digestive conditions outside of those observed in humans. This study sought to assess IC bioaccessibility and Caco-2 cell uptake using physiologically relevant digestive solutions, pH, and incubation time, as compared to other iron sources (i.e., FeSO4, and hemoglobin (Hb)). Co-digestion with ascorbic acid (AA) and albumin was also investigated. Following gastric, duodenal, and jejunal digestion, IC-bound iron was less bioaccessible than iron delivered as FeSO4, and IC-bound iron was less bioaccessible than Hb-bound iron. IC-bound iron bioaccessibility was not affected by AA and was enhanced 2x when co-digested with a low dose of albumin. However, Caco-2 cell incubation with IC-containing digesta increased cell ferritin 2.5x more than FeSO4 alone, and less than Hb. IC with AA or with 400 mg albumin also increased cell ferritin more than IC alone, with the greatest increases observed following incubation of digesta containing IC + AA + 400 mg albumin. These results suggest IC can serve as an improved source of iron for supplementation as compared to FeSO4. These results also support further in vivo investigations of IC-based iron delivery in populations at risk of iron deficiency.

Modulation of microglia activation by the ascorbic acid transporter SVCT2.

Neuroinflammation is a major characteristic of pathology in several neurodegenerative diseases. Microglia, the brain's resident myeloid cells, shift between activation states under neuroinflammatory conditions, both responding to, but also driving damage in the brain. Vitamin C (ascorbate) is an essential antioxidant for central nervous system function that may have a specific role in the neuroinflammatory response. Uptake of ascorbate throughout the central nervous system is facilitated by the sodium-dependent vitamin C transporter 2 (SVCT2). SVCT2 transports the reduced form of ascorbate into neurons and microglia, however the contribution of altered SVCT2 expression to the neuroinflammatory response in microglia is not well understood. In this study we demonstrate that SVCT2 expression modifies microglial response, as shown through changes in cell morphology and mRNA expression, following a mild traumatic brain injury (mTBI) in mice with decreased or increased expression of SVCT2. Results were supported by in vitro studies in an immortalized microglial cell line and in primary microglial cultures derived from SVCT2-heterozygous and transgenic animals. Overall, this work demonstrates the importance of SVCT2 and ascorbate in modulating the microglial response to mTBI and suggests a potential role for both in response to neuroinflammatory challenges.

Microwave seed priming and ascorbic acid assisted phytoextraction of heavy metals from surgical industry effluents through spinach.

The prevalence of inorganic pollutants in the environment, including heavy metals (HMs), necessitates a sustainable and cost-effective solution to mitigate their impacts on the environment and living organisms. The present research aimed to assess the phytoextraction capability of spinach (Spinach oleracea L.), under the combined effects of ascorbic acid (AA) and microwave (MW) irradiation amendments, cultivated using surgical processing wastewater. In a preliminary study, spinach seeds were exposed to MW radiations at 2.45 GHz for different durations (15, 30, 45, 60, and 90 seconds). Maximum germination was observed after the 30 seconds of radiation exposure. Healthy spinach seeds treated with MW radiations for 30 s were cultivated in the sand for two weeks, after which juvenile plants were transferred to a hydroponic system. Surgical industry wastewater in different concentrations (25 %, 50 %, 75 %, 100 %) and AA (10 mM) were provided to both MW-treated and untreated plants. The results revealed that MW-treatment significantly enhanced the plant growth, biomass, antioxidant enzyme activities and photosynthetic pigments, while untreated plants exhibited increased reactive oxygen species (ROS) and electrolyte leakage (EL) compared with their controls. The addition of AA to both MW-treated and untreated plants improved their antioxidative defense capacity under HMs-induced stress. MW-treated spinach plants, under AA application, demonstrated relatively higher concentrations and accumulation of HMs including lead (Pb), cadmium (Cd) and nickel (Ni). Specifically, MW-treated plants with AA amendment showed a significant increase in Pb concentration by 188 % in leaves, Cd by 98 %, and Ni by 102 % in roots. Additionally, the accumulation of Ni increased by 174 % in leaves, Cd by 168 % in roots, and Pb by 185 % in the stem of spinach plant tissues compared to MW-untreated plants. These findings suggested that combining AA with MW irradiation of seeds could be a beneficial strategy for increasing the phytoextraction of HMs from wastewater and improving overall plant health undergoing HMs stress.

TET3 downregulation and low 5-hydroxymethylcytosine are epigenetic signatures of head and neck carcinoma.

BACKGROUND: Ten-eleven translocases (TETs) are enzymes responsible for demethylation processes, playing a crucial role in maintaining the body's methylation balance. Dysregulation of TET expression can lead to abnormal methylation levels. Isocitrate dehydrogenases (IDH) are upstream genes involved in Kreb cycle responsible for production of α-ketoglutarate (α-KG). α-KG and vitamin C are cofactors of TET3 enzyme. There is limited data on the relationship between TET3 and its cofactor Vitamin C in head and neck carcinoma (H&NC). METHODS AND RESULTS: In this study, we have investigated the expression of the TET3 gene along with IDH1/2 genes involved in the Krebs cycle in the peripheral blood of 32 H&NC patients compared to 32 healthy controls. We estimated serum levels of TET3 protein and vitamin C and 5-hydroxymethylcytosine (5-hmC) percentage in DNA isolated from EDTA blood samples. Our findings revealed that TET3 and IDH1/2 were downregulated in H&NC patients compared to healthy controls. Serum levels of TET3 and Vitamin C were low in H&NC patients compared to healthy controls. Diminished levels of percentage 5-hmC were detected in EDTA blood samples of H&NC patients compared to controls. Spearman correlation analysis revealed a significant positive correlation between TET3 levels, vitamin C levels and 5-hmC percentage. CONCLUSION: The low levels of Vitamin C are believed to contribute to decreased activity of the TET3 gene and less conversion of 5-methylcytosine (5-mC) to 5-hmC. Dietary supplementation of Vitamin C may increase TET3 activity.