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In this work, Green and sustainable sorption method for Li(I) from nitrate medium using a solid functionalised Na+ form of Dowex 50WX8 resin was developed. Scanning electron microscope (SEM), Fourier transform infrared (FT-IR), and energy-dispersive X-ray (EDX) techniques were used for characterisations of Dowex resin before and after the loading of Li ions. The batch technique describes the effects of the different parameters affecting the sorption process was carried out. The batch experiments were studied using 100 mg/L Li(I) at the selected sorption conditions (shaking time = 30 min, adsorbent weight = 0.125 g, temperature= 25°C, and pH = 1) which give sorption efficiency = 60%. The experimental maximum sorption capacity of Dowex 50WX8-Na+ after one sorption cycle was found to be 15 mg/g. Thermodynamic studies indicated that the sorption of the Li(I) on Dowex 50WX8-Na+ resin is physical and exothermic adsorption with spontaneous nature. The maximum desorption efficiency of 85% and 70% was achieved with 1.0 M phosphoric acid and oxalic acid, respectively. An industrial application for green recycling and recovery of Li(I) from spent Li-ion batteries (LIBs) through its leaching with ascorbic acid (1.25 M) and H2O2 (10%) was performed. Lithium ions were selectively recovered (uptake %= 96%) from the spent Li-ions batteries leachate which contains associated metal ions (Co, Ni, and Mn) with Dowex 50Wx8-Na+ sorbent. A flow sheet that presents the performance of industrial method developed for the recycling and separation of Li(I) from (LIBs) under optimum sorption conditions is also provided. [ABSTRACT FROM AUTHOR]

Drought is an abiotic disturbance that reduces photosynthesis, plant growth, and crop yield. Ascorbic acid (AsA) was utilized as a seed preconditioning agent to assist broccoli (Brassica oleracea var. italica) in resisting drought. However, the precise mechanism by which AsA improves seedlings' development remains unknown. One hypothesis is that AsA works via antioxidant mechanisms and reduces oxidative stress. This study aims to confirm the effect of varied concentrations of AsA (control, 0 ppm, 1 ppm, or 10 ppm) on seedling growth and changes in the antioxidant status of broccoli seedlings under regular watering or drought stress. AsA increased shoot dry mass, leaf area, net photosynthesis, and water use efficiency in watered and drought-stressed seedlings. AsA significantly (p < 0.001) increased carotenoid content in watered and drought-stressed seedlings by approximately 27% and 111%, respectively. Drought increased chlorophyll b, flavonoids, phenolics, ascorbate, and hydrogen peroxide production in control seedlings, but either had no effect or less effect on plants preconditioned with 10 ppm AsA. There was no improvement in reactive oxygen species scavenging in AsA-preconditioned seedlings compared to the control. The absence or reduction in biochemical indicators of stress suggests that preconditioned broccoli seedlings do not perceive stress the same as control seedlings. In conclusion, the consistent increase in carotenoid concentration suggests that carotenoids play some role in the preconditioning response, though the exact mechanism remains unknown. [ABSTRACT FROM AUTHOR]

Fulvic acid (FA) is an active humic substance and is found to improve the antioxidant defence system under unfavourable conditions. Dunaliella salina is a unicellular microalga and is a rich source of β-carotene. In this study the impact of fulvic acid (FA) was investigated on some physiological parameters, H2O2 production, antioxidant metabolites, and enzymatic responses related to the ascorbate (ASA)-glutathione (GSH) pathway in D. salina. Results showed that 100 mg FA L−1 maintained the D. salina cell growth compared to control, and exhibited as a suitable treatment to induce carotenoids compared to 50 FA mg L−1. However, 200 FA mg L−1 significantly decreased the cell biomass. FA (100 mg L−1) enhanced the total carotenoids (3.92 pg cell−1), β-carotene (2.46 pg cell−1), and lutein (0.81 pg cell−1) after 7 days, which was accompanied by a reduction in the chlorophyll a and b. Cell number did not change significantly under FA and cells trended to be round in shape after 7 days. Protein content showed an insignificant change, while H2O2 level was promoted by FA treatment, which was related to the regulation of the ASA-GSH pathway. The activity of ascorbate peroxidase, superoxide dismutase, and dehydroascorbate reductase was more promoted in the FA-treated cells, while glutathione reductase activity and glutathione content were just induced under Sevier oxidative conditions. The findings of this research suggest new insights into the inducing impact of FA on the ASA-GSH pathway and carotenoid biosynthesis to regulate the ROS level in D. salina. [ABSTRACT FROM AUTHOR]

In 1983, Linus Pauling and colleagues reported about enhanced antitumor activity of the Cu(II) complex of the simplest ATCUN (amino terminal Cu(II) and Ni(II)-binding motif) peptide (NH2-Gly-Gly-His-COOH, GGH) in the presence of ascorbate as an additive. In the following 4 decades, structural modifications of this complex were implemented, however, anticancer activity could not be significantly increased. This has led to neglecting the ATCUN motif and its Cu(II) complexes as potential chemotherapeutic agents. Furthermore, the addition of ascorbate with its positive effect on the anticancer activity has fallen into oblivion. In this work, we compared Cu(II) GGH with Cu(II) ATCUN peptides bearing β-Ala instead of Gly at the 2nd position of the peptide sequence regarding their in vitro complex stability and cytotoxicity (MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and annexin V-FITC (fluorescein isothiocyanate) apoptosis assay) towards three cancer cell lines (AGS, HeLa and NCI-N87). Such an exchange of amino acids led to an up to three-fold higher cytotoxic effect in the presence of ascorbate. We thus achieved a significant increase in the otherwise moderate cytotoxicity of Cu(II) ATCUN-like complexes. Lipophilicity assays (n-octanol/water coefficient, log P values) of the studied complexes were used to evaluate differences in the antiproliferative activity. [ABSTRACT FROM AUTHOR]

Indoleamine 2,3‐dioxygenase (IDO) is a monomeric heme enzyme that catalyzes the oxidative cleavage of tryptophan (L‐Trp) to form N‐formyl‐kynurenine. Similar to other heme proteins, IDO only binds to O2 when the heme iron is ferrous (FeII), thereby rendering the enzyme active. Thus, ascorbate (Asc, a reducing agent) and methylene blue (MB, an electron carrier) are commonly added to in vitro IDO assay systems. However, Asc and MB have been recently reported to significantly impact the measurement of the enzymatic parameters of vertebrate IDO. Aspergillus fumigatus is a filamentous fungus and the most common cause of invasive aspergillosis; it has three IDO genes (IDOα, IDOβ, and IDOγ). The FeII–O2 IDOs of A. fumigatus, particularly FeII–O2 IDOγ, have relatively long half‐lives in their autoxidation; however, the autoxidation was accelerated by Asc. Similar to vertebrate IDOs, Asc acted as a competitive (or mixed‐competitive) inhibitor of the IDOs of A. fumigatus. A positive correlation (in the order of IDOγ > IDOβ > IDOα) was observed between the inhibitory sensitivity of the IDOs to Asc and the facilitation of their autoxidation by Asc. The FeII–O2 IDO can repeat the dioxygenase reaction as long as it reacts with L‐Trp; however, substrate‐free FeII–O2 IDO is converted into inactive FeIII–IDO by autoxidation. Thus, L‐Trp (which keeps the IDO active) competes with Asc (which inactivates IDO by accelerating autoxidation). This is probably why Asc, which is structurally quite different from L‐Trp, appears to function as a competitive (or mixed‐competitive) inhibitor of IDOs. [ABSTRACT FROM AUTHOR]

Contamination of agricultural products with Cadmium (Cd) is a global problem that should be considered for minimizing the risks to human health. Considering the potential effects of SiNPs in decreasing abiotic stress, a study was conducted to investigate the effect of SiNPs in the reduction of Cd stress on Solanum lycopersicum. SiNPs was used at 0, 25, 50 and 100 mg/l and CdCl2 at 0, 100 and 200 µM concentrations. The results showed that Cd stress caused a significant decrease in dry weight, content of GSH, ASA, significently increasing the activity of GR, APX, GST, SOD, as well as content of H2O2, MDA, proline, and GABA in shoots and roots compared to the control. SiNPs significantly increased shoot and root dry weight compared to the control. As a coenzyme, SiNPs induced the activity of antioxidant enzymes and significantly increased GST and GR gene expression compared to the control. SiNPs also caused a substantial increase in the content of ASA, GSH, proline and GABA compared to the control. By inducing the activity of antioxidant enzymes and metabolites of the ascorbate-glutathione (ASA-GSH) cycle, SiNPs removed a large content of H2O2 and significantly reduced the MDA content, and as a result led to the stability of cell membrane under Cd stress. Induction of ASA-GSH, GABA and SOD cycle by SiNPs clearly showed that SiNPs could be a potential tool to alleviate Cd stress in plants cultivated in areas contaminated with this heavy metal. [ABSTRACT FROM AUTHOR]

Salinity represents a significant abiotic stress that markedly influences plant growth through osmotic stress induction. Plants commonly undergo osmotic adaptation when subjected to prolonged periods of saline stress. The current experiments were conducted on five wheat (Triticum aestivum L.) genotypes with contrasting salt tolerance capacities - Mirbashir 128, Gobustan, Gyzyl bughda, Fatima, and Zirva 80 under salinity stress caused by 150 mmol NaCl. The relative water content and osmotic potential were found to decrease significantly in salinity-sensitive genotypes (Fatima and Zirva 80) compared to salinity-tolerant ones (Mirbashir 128, Gobustan, and Gyzyl bughda) when treated with 150 mmol NaCl. Salinity also caused the accumulation of soluble sugars and proline, the amounts of which were observed to be higher in salinity-tolerant genotypes than sensitive ones, while lipid peroxidation was higher in salinity-sensitive genotypes. In salinity-tolerant genotypes, 150 mmol NaCl caused increased antioxidant enzyme activities and accumulation of flavonoids, including anthocyanins, confirming the rapid development of the stress reactions in these plants. Differences in the osmoregulation indicators and antioxidant responses between salinity-tolerant and sensitive plants are assumed to be related to their salinity-tolerance traits. This investigation provides pivotal foundational insights for enhancing the salt tolerance of wheat genotypes, thereby potentially enhancing both yield and quality in diverse wheat cultivars thriving in saline environments.

Brain radiation is a crucial tool in neuro-oncology for enhancing local tumor control, but it can lead to mild-to-profound and progressive impairments in cognitive function. Radiation-induced brain injury is a significant adverse effect of radiotherapy for cranioencephalic tumors, primarily caused by indirect cellular damage through the formation of free radicals. This results in late neurotoxicity manifesting as cognitive impairment due to free radical production. The aim of this review is to highlight the role of different substances, such as drugs used in the clinical setting and antioxidants such as ascorbate, in reducing the neurotoxicity associated with radiation-induced brain injury. Currently, there is mainly preclinical and clinical evidence supporting the benefit of these interventions, representing a cost-effective and straightforward neuroprotective strategy.

Abstract Contamination of agricultural products with Cadmium (Cd) is a global problem that should be considered for minimizing the risks to human health. Considering the potential effects of SiNPs in decreasing abiotic stress, a study was conducted to investigate the effect of SiNPs in the reduction of Cd stress on Solanum lycopersicum. SiNPs was used at 0, 25, 50 and 100 mg/l and CdCl2 at 0, 100 and 200 µM concentrations. The results showed that Cd stress caused a significant decrease in dry weight, content of GSH, ASA, significently increasing the activity of GR, APX, GST, SOD, as well as content of H2O2, MDA, proline, and GABA in shoots and roots compared to the control. SiNPs significantly increased shoot and root dry weight compared to the control. As a coenzyme, SiNPs induced the activity of antioxidant enzymes and significantly increased GST and GR gene expression compared to the control. SiNPs also caused a substantial increase in the content of ASA, GSH, proline and GABA compared to the control. By inducing the activity of antioxidant enzymes and metabolites of the ascorbate-glutathione (ASA-GSH) cycle, SiNPs removed a large content of H2O2 and significantly reduced the MDA content, and as a result led to the stability of cell membrane under Cd stress. Induction of ASA-GSH, GABA and SOD cycle by SiNPs clearly showed that SiNPs could be a potential tool to alleviate Cd stress in plants cultivated in areas contaminated with this heavy metal.

Introduction: Leiomyosarcoma (LMS) is a malignancy with smooth muscle differentiation. Metastatic LMS is associated with poor prognosis and limited efficacy of systemic treatment. Novel treatment modalities are desperately needed for this entity. Case Presentation: We report the first use of pembrolizumab plus pharmacologic ascorbate in 3 patients with metastatic LMS. All cases resulted in persistent objective responses and disease control significantly better than has been reported with chemotherapy or other immunotherapeutic approaches. Three patients with metastatic LMS, one each of uterine, vascular, and soft tissue origin, were treated with pembrolizumab plus pharmacologic ascorbate. The patient with uterine LMS received combination therapy at presentation and had persistent response for 12 months, which is ongoing. The patient with metastatic LMS of the inferior vena cava received combination therapy at presentation and had persistent response for 12 months, at which time new metastases were found. The patient with soft tissue LMS had disease progression on pembrolizumab monotherapy prior to the addition of ascorbate, after which she had a 17-month response, which is ongoing. No side effects attributed to treatment were reported. Conclusion: Pembrolizumab plus pharmacologic ascorbate is a novel immunotherapeutic approach and warrants further study in LMS.

The haemorrhagic features of viral haemorrhagic fevers may be caused by common patterns of metabolic disturbances of the glucose and ascorbate homeostasis. Haemorrhages and vasculature disfunctions are a clinical feature not only of viral haemorrhagic fevers, but also in scurvy, diabetes and thrombotic microangiopathic haemolytic anaemia. Interestingly, the expression of glucose and ascorbate transporter Glut-1 on the erythrocyte membrane is associated with the inability to synthesize ascorbate and is restricted to that very species that are susceptible to filoviruses (primates, humans and fruit bats). Glut-1 may play a pivotal role in haemorrhagic fever pathogenesis. TIM-1 and TAM receptors have been recognized to enhance entry of Ebola, Lassa and Dengue viruses and viral interferences with TIM-1 could disturb its function, disturbing the expression of Glut-1. In those species not able to synthesize ascorbate and expressing Glut-1 on erythrocytes virus could interact with Glut-1 or other functionally related protein, and the influx of glucose into the cells would be severely impaired. As a consequence, transient hyperglycemia and a marked oxidative stress coupled with the high levels of glucose in plasma would be established, and then promote the activation of NF–κB transcription, exacerbating a pro-inflammatory response mediated by cytokines and chemokines: The inability to synthesize ascorbate is an Achilles Heel when trying to counteract the oxidative stress.

Thyroid cancer (TC) is the most common endocrine malignancy, with an increased global incidence in recent decades, despite a substantially unchanged survival. While TC has an excellent overall prognosis, some types of TC are associated with worse patient outcomes, depending on the genetic setting. Furthermore, oxidative stress is related to more aggressive features of TC. Vitamin C, an essential nutrient provided with food or as a dietary supplement, is a well-known antioxidant and a scavenger of reactive oxygen species; however, at high doses, it can induce pro-oxidant effects, acting through multiple biological mechanisms that play a crucial role in killing cancer cells. Although experimental data and, less consistently, clinical studies, suggest the possibility of antineoplastic effects of vitamin C at pharmacological doses, the antitumor efficacy of this nutrient in TC remains at least partly unexplored. Therefore, this review discusses the current state of knowledge on the role of vitamin C, alone or in combination with other conventional therapies, in the management of TC, the mechanisms underlying this association, and the perspectives that may emerge in TC treatment strategies, and, also, in light of the development of novel functional foods useful to this extent, by implementing novel sensory analysis strategies. [ABSTRACT FROM AUTHOR]

Fruits with a high content of biologically active compounds are essential in preventing many diseases. Therefore, the interest in searching for and testing new plant sources for bioactive constituents remains strong. Although many publications on individual species exist, their results are difficult to compare directly due to varying methods and conditions of analysis. Only a few studies have investigated many different species in a single analysis. Therefore, we examined and compared 21 different genotypes, using various measurement methods for total phenolic content (TPC) (Folin–Ciocalteu, FBBB), total antioxidant capacity (ABTS, FRAP, DPPH), and the HPLC technique for the total ascorbate concentration in freshly harvested fruits. One-way ANOVA, Principal Component Analysis, and Pearson Correlation were used to analyse and compare the results. The tested samples showed significant differences in TPC, ascorbate content, and antioxidant capacity. The correlation between the content of bioactive compounds and antioxidant capacity depended on the analytical methods, with results obtained using the FRAP test being the most strongly correlated. Due to higher levels of polyphenols, ascorbate, and antioxidant potential, the most promising species for further evaluation appear to be Chaenomeles × californica, Actinidia kolomikta, Mespilus germanica, and ×Sorboaronia fallax. [ABSTRACT FROM AUTHOR]

The Latex Diagnosis (LD) is performed through the determination of dry rubber (DRC), sucrose (Suc), inorganic phosphorus (Pi) and thiol (RSH) contents. It is carried out through the colorimetric method using a single cuvette spectrophotometer, which is time-consuming and requires a high volume of chemicals. It also needs to be executed as soon as the samples are collected so that limits the adoption of LD. The adaptation of the protocol to a multiplate reader and suitable conservation aimed to overcome the limitations. The experiments were carried out at the Indonesian Rubber Research Institute, Sembawa, Palembang, and Research Center for Biotechnology, Universitas Gadjah Mada, Yogyakarta. Various combinations of solution volumes, adapted from standard protocol, were tested. The closest slope of the standard curve to control was then applied to 7 randomly selected trees. The result showed that for Suc, the composition of 10 µL samples, 30 µL of 2.5 % TCA and 210 µL anthrone reagent was suitable for determination using a multiplate reader. The combination of 40 µL of sample, 85 µL of 2.5 % TCA and 125 µL mL FeSO4 solution was suitable for Pi determination, while 100 µL samples, 5 µL DNTB and 100 µL Tris is recommended for RSH. The measurement using a multiplate reader resulted in comparable contents (average deviations were 1.83, 2.69 and 3.51 % for Suc, Pi, and RSH, respectively), lower time and chemicals consumptions, and a larger number of sample handling compared to single cuvette method. This study also tested the effect of freeze-drying for sample conservation. The result indicated that freezedrying was able to maintain the Pi level (deviation 0.93 %). However, it increased Suc (deviation 19.43 %) and decreased ascorbate (AsA) significantly (deviation 43.60 %); therefore, freeze-drying might not be suitable for conserving serum samples in the LD method. [ABSTRACT FROM AUTHOR]

Arugula is susceptible to postharvest deterioration. We tested the impact of exogenous antioxidant (i.e., ergothioneine and glutathione) dip solutions on arugula quality during storage at 4 °C or 10 °C for up to 17 days relative to a non-antioxidant treatment. Leaves from each dip treatment and storage temperature were assessed for visual quality and endogenous antioxidant metabolite profiles. Overall, leaf discolouration, wilting, and decay were more rapid at 10 °C than at 4 °C. Both antioxidant treatments limited leaf discolouration at 4 °C. Exogenous ergothioneine reduced wilting at 4 °C, whereas exogenous glutathione limited the incidence of leaf decay. At 10 °C, glutathione reduced the incidence of discolouration and decay, whereas both antioxidant dip treatments limited the decline in leaf yellowing. Ergothioneine was solely detected in ergothioneine-treated leaves; a decrease occurred within the first two days of storage but was unchanged thereafter. Although both antioxidant treatments did not affect endogenous glutathione concentrations at either storage temperature, glutathione disulfide was stable within the glutathione-treated leaves, whereas it increased in the other treatments. Ascorbate degradation was delayed in ergothioneine-treated leaves at 4 °C relative to all other treatments, whereas both antioxidant treatments little affected ascorbate metabolism in leaves stored at 10 °C. [ABSTRACT FROM AUTHOR]

Several studies have demonstrated, both in vitro and in animal models, the anti-tumor efficacy of high-dose ascorbate treatment against a variety of tumor entities, including glioblastoma, the most common and aggressive primary malignant brain tumor. The aim of this study was to investigate the effects of high-dose ascorbate as well as dehydroascorbic acid on human glioblastoma cell lines and to evaluate different treatment conditions for the combined administration of ascorbate with magnesium (Mg2+) and iron (Fe3+). Intracellular levels of reactive oxygen species and the induction of cell death following ascorbate treatment were also investigated. We demonstrated high cytotoxicity and antiproliferative efficacy of high-dose ascorbate in human glioblastoma cells, whereas much weaker effects were observed for dehydroascorbic acid. Ascorbate-induced cell death was independent of apoptosis. Both the reduction in cell viability and the ascorbate-induced generation of intracellular reactive oxygen species could be significantly increased by incubating the cells with Fe3+ before ascorbate treatment. This work demonstrates, for the first time, an increase in ascorbate-induced intracellular ROS formation and cytotoxicity in human glioblastoma cells by pre-treatment of the tumor cells with ferric iron, as well as caspase-3 independence of cell death induced by high-dose ascorbate. Instead, the cell death mechanism caused by high-dose ascorbate in glioblastoma cells shows evidence of ferroptosis. The results of the present work provide insights into the efficacy and mode of action of pharmacological ascorbate for the therapy of glioblastoma, as well as indications for possible approaches to increase the effectiveness of ascorbate treatment. [ABSTRACT FROM AUTHOR]

Antioxidant responses play a crucial role in combating free radical damage induced by drought stress. In guar plants, the antioxidant mechanism is crucial for stress tolerance; however, the specific antioxidant response in individual guar genotypes remains unclear. This study investigates the physiological, biochemical, and transcriptional responses of four guar genotypes to drought stress by maintaining soil moisture content (SMC) at varying levels: control (100% FC), medium (60% FC), and severe (20% FC). Among the genotypes examined, HG-563 and HG-365 exhibit higher leaf relative water content (RWC) and total chlorophyll/carotenoid content, indicating lesser inhibition under drought stress compared to HG-75 and RGC-936. Notably, HG-563 and HG-365 demonstrate a significant increase in activities of key antioxidant enzymes such as superoxide dismutase (SOD), peroxidase (POD), ascorbate (AsA), and glutathione (GSH) during medium and severe drought stress conditions. This observation is further supported by in-gel activity assays revealing a notable upregulation of Cu/ZnSOD and POD isozymes, which is consistent with higher expression levels of Cu/ZnSOD and POD genes at the transcriptional level. Consequently, these results highlight the comparatively higher drought tolerance of HG-563 and HG-365 genotypes. The findings shed light on the activation of antioxidant responses in drought-tolerant guar genotypes under stress conditions, emphasizing the crucial role of antioxidant enzymes in the drought tolerance mechanism of guar plants. [ABSTRACT FROM AUTHOR]

Curcumacaesia Roxb., a critically endangered herb in the Zingiberaceae family, can be conserved through microrhizomes, which are easily transported, germinate like seeds, and are independent of seasonal variations. The current investigation attempts to induce microrhizomes of this endangered herb for conservation purpose using high concentration of sucrose. To encourage the establishment of microrhizomes, six-month-old cultures of C.caesia were transferred to Murashige and Skoog supplemented with containing 8 mg L−1 benzyladenine, 8 mg L−1 kinetin, 100 mg L−1 citric acid, 200 mg L−1 adenine sulphate, and 2 mg L−1 indole-3-acetic acid (standard medium). For this, standard medium was examined with sucrose concentrations of 3%, 6%, 9%, and 12%. The standard medium with 9% sucrose showed the highest rate of microrhizome formation (now referred as microrhizome production medium, MPM). During acclimatization, the survival rate of microrhizomes exceeded 90%. The physiology behind the microrhizome formation was also evaluated using enzymatic and non-enzymatic tests on days 0, 30, and 60 after inoculation. Superoxide dismutase activity, an enzymatic defence molecule, and total soluble sugar and ascorbate content, a non-enzymatic defence molecule, both increased in the MPM microrhizomes relative to the control [shoot multiplication medium (standard medium with 3% sucrose) at day 0]. Further, protein, 2-thiobarbituric acid reactive substances, and hydrogen peroxide content also increased. The biochemical results proved that 9% sucrose in MPM induces osmotic stress which eventually led to the formation of C.caesia microrhizomes, an in vitro storage organ. [ABSTRACT FROM AUTHOR]

Introduction: Leiomyosarcoma (LMS) is a malignancy with smooth muscle differentiation. Metastatic LMS is associated with poor prognosis and limited efficacy of systemic treatment. Novel treatment modalities are desperately needed for this entity. Case Presentation: We report the first use of pembrolizumab plus pharmacologic ascorbate in 3 patients with metastatic LMS. All cases resulted in persistent objective responses and disease control significantly better than has been reported with chemotherapy or other immunotherapeutic approaches. Three patients with metastatic LMS, one each of uterine, vascular, and soft tissue origin, were treated with pembrolizumab plus pharmacologic ascorbate. The patient with uterine LMS received combination therapy at presentation and had persistent response for 12 months, which is ongoing. The patient with metastatic LMS of the inferior vena cava received combination therapy at presentation and had persistent response for 12 months, at which time new metastases were found. The patient with soft tissue LMS had disease progression on pembrolizumab monotherapy prior to the addition of ascorbate, after which she had a 17-month response, which is ongoing. No side effects attributed to treatment were reported. Conclusion: Pembrolizumab plus pharmacologic ascorbate is a novel immunotherapeutic approach and warrants further study in LMS. [ABSTRACT FROM AUTHOR]

The superoxide anion radical (O2·−) is a one-electron reduction product of molecular oxygen. Compared with other forms of reactive oxygen species (ROS), superoxide has limited reactivity. Nevertheless, superoxide reacts with nitric oxide, ascorbate, and the iron moieties of [Fe–S] cluster-containing proteins. Superoxide has largely been neglected as a signalling molecule in the plant literature in favour of the most stable ROS form, hydrogen peroxide. However, superoxide can accumulate in plant cells, particularly in meristems, where superoxide dismutase activity and ascorbate accumulation are limited (or absent), or when superoxide is generated within the lipid environment of membranes. Moreover, oxidation of the nucleus in response to environmental stresses is a widespread phenomenon. Superoxide is generated in many intracellular compartments including mitochondria, chloroplasts, and on the apoplastic/cell wall face of the plasma membrane. However, nuclear superoxide production and functions remain poorly documented in plants. Accumulating evidence suggests that the nuclear pools of antioxidants such as glutathione are discrete and separate from the cytosolic pools, allowing compartment-specific signalling in the nucleus. We consider the potential mechanisms of superoxide generation and targets in the nucleus, together with the importance of antioxidant processing in regulating superoxide signalling. [ABSTRACT FROM AUTHOR]

• Ascorbic acid transport into cells via SVCT2 may mediate microglial inflammatory response after traumatic brain injury. • SVCT2 expression impacts microglial inflammatory cytokine activation following LPS administration. • SVCT2 over-expression may protect against microglial inflammatory changes. • Maintaining proper ascorbic acid levels and SVCT2 expression supports regulation of microglial response to challenge. 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. [ABSTRACT FROM AUTHOR]

The mechanisms by which megadose sodium ascorbate improves clinical status in experimental sepsis is unclear. We determined its effects on cerebral perfusion, oxygenation, and temperature, and plasma levels of inflammatory biomarkers, nitrates, nitrites, and ascorbate in ovine Gram-negative sepsis. Sepsis was induced by i.v. infusion of live Escherichia coli for 31 h in unanaesthetised Merino ewes instrumented with a combination sensor in the frontal cerebral cortex to measure tissue perfusion, oxygenation, and temperature. Fluid resuscitation at 23 h was followed by i.v. megadose sodium ascorbate (0.5 g kg−1 over 30 min+0.5 g kg−1 h−1 for 6.5 h) or vehicle (n =6 per group). Norepinephrine was titrated to restore mean arterial pressure (MAP) to 70–80 mm Hg. At 23 h of sepsis, MAP (mean [ sem ]: 85 [2] to 64 [2] mm Hg) and plasma ascorbate (27 [2] to 15 [1] μM) decreased (both P <0.001). Cerebral ischaemia (901 [58] to 396 [40] units), hypoxia (34 [1] to 19 [3] mm Hg), and hyperthermia (39.5 [0.1]°C to 40.8 [0.1]°C) (all P <0.001) developed, accompanied by malaise and lethargy. Sodium ascorbate restored cerebral perfusion (703 [121] units], oxygenation (30 [2] mm Hg), temperature (39.2 [0.1]°C) (all P Treatment <0.05), and the behavioural state to normal. Sodium ascorbate slightly reduced the sepsis-induced increase in interleukin-6, returned VEGF-A to normal (both P GroupxTime <0.01), and increased plasma ascorbate (20 000 [300] μM; P Group <0.001). The effects of sodium ascorbate were not reproduced by equimolar sodium bicarbonate. Megadose sodium ascorbate rapidly reversed sepsis-induced cerebral ischaemia, hypoxia, hyperthermia, and sickness behaviour. These effects were not reproduced by an equimolar sodium load. [ABSTRACT FROM AUTHOR]

The haemorrhagic features of viral haemorrhagic fevers may be caused by common patterns of metabolic disturbances of the glucose and ascorbate homeostasis. Haemorrhages and vasculature disfunctions are a clinical feature not only of viral haemorrhagic fevers, but also in scurvy, diabetes and thrombotic microangiopathic haemolytic anaemia. Interestingly, the expression of glucose and ascorbate transporter Glut-1 on the erythrocyte membrane is associated with the inability to synthesize ascorbate and is restricted to that very species that are susceptible to filoviruses (primates, humans and fruit bats). Glut-1 may play a pivotal role in haemorrhagic fever pathogenesis. TIM-1 and TAM receptors have been recognized to enhance entry of Ebola, Lassa and Dengue viruses and viral interferences with TIM-1 could disturb its function, disturbing the expression of Glut-1. In those species not able to synthesize ascorbate and expressing Glut-1 on erythrocytes virus could interact with Glut-1 or other functionally related protein, and the influx of glucose into the cells would be severely impaired. As a consequence, transient hyperglycemia and a marked oxidative stress coupled with the high levels of glucose in plasma would be established, and then promote the activation of NF–κB transcription, exacerbating a pro-inflammatory response mediated by cytokines and chemokines: The inability to synthesize ascorbate is an Achilles Heel when trying to counteract the oxidative stress.

Vitamin C is one of the most well-known and most frequently used substances found in various pharmaceutical preparations. Patients consider it as a safe compound with multidirectional beneficial effects, while chemists have been presenting various possibilities for its determination for many years. The aim of this review is to present the current range of drugs and dietary supplements containing vitamin C available in Poland, divided into appropriate categories, taking into account doses, forms and other ingredients. The second goal is to summarize the main analytical methods for determining the content of ascorbic acid. A review of available preparations showed disproportions between a small group of drugs and a very large group of dietary supplements, which turned out to be significantly diversified in various aspects. In turn, the review of analytical methods clearly indicates the dominant share of spectroscopic ones and the fact that researchers focus primarily on improving basic, commonly known techniques.

The haemorrhagic features of viral haemorrhagic fevers may be caused by common patterns of metabolic disturbances of the glucose and ascorbate homeostasis. Haemorrhages and vasculature disfunctions are a clinical feature not only of viral haemorrhagic fevers, but also in scurvy, diabetes and thrombotic microangiopathic haemolytic anaemia. Interestingly, the expression of glucose and ascorbate transporter Glut-1 on the erythrocyte membrane is associated with the inability to synthesize ascorbate and is restricted to that very species that are susceptible to filoviruses (primates, humans and fruit bats). Glut-1 may play a pivotal role in haemorrhagic fever pathogenesis. TIM-1 and TAM receptors have been recognized to enhance entry of Ebola, Lassa and Dengue viruses and viral interferences with TIM-1 could disturb its function, disturbing the expression of Glut-1. In those species not able to synthesize ascorbate and expressing Glut-1 on erythrocytes virus could interact with Glut-1 or other functionally related protein, and the influx of glucose into the cells would be severely impaired. As a consequence, transient hyperglycemia and a marked oxidative stress coupled with the high levels of glucose in plasma would be established, and then promote the activation of NF–κB transcription, exacerbating a pro-inflammatory response mediated by cytokines and chemokines: The inability to synthesize ascorbate is an Achilles Heel when trying to counteract the oxidative stress.

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. [ABSTRACT FROM AUTHOR]

Lipoic acid (LA), a unique antioxidant compound, can stimulate the antioxidant defense system in plants subjected to abiotic stresses. We aimed to determine the role of LA in induction of the antioxidant system at lower reactive oxygen species (ROS), ascorbate (ASC) and glutathione (GSH) levels in osmotic-stressed maize (Zea mays L.). For this purpose, ROS, GSH and ASC contents were decreased using N,N'‑dimethylthiourea (DMTU), L-buthionine sulfoximine (BSO) and acriflavine (AF), respectively. Pots containing 21-day-old seedlings were divided into nine groups consisting of a non-stressed group; polyethylene glycol6000 (PEG)-induced osmotic stress (PEG) group, LA, DMTU, BSO and AF treatment groups; and DMTU, BSO, and AF-combined LA treatment groups under osmotic stress. ROS contents and membrane damage after the DMTU, BSO, and AF-combined LA treatments were lower than those after the DMTU, BSO, and AF treatments, respectively. Moreover, the LA treatments in combination with DMTU, BSO and AF increased dry weight, activities of antioxidant enzymes (superoxide dismutase, catalase, ascorbate peroxidase, glutathione reductase, monodehydroascorbate reductase and dehydroascorbate reductase), and contents of GSH, ASC, and LA compared to the DMTU, BSO and AF treatments. Additionally, the relative expression levels of SUPEROXIDE DISMUTASE, CATALASE1 and ASCORBATE PEROXIDASE1 genes were consistent with the findings for their related antioxidant enzyme activities. These results indicated that LA could adjust ROS level and maintain stimulation of the antioxidant system at lower ROS, GSH, and ASC levels in osmotic stressed maize. Furthermore, LA may play a signaling role and assume the function of ASC and GSH in maize under PEG-induced osmotic stress. [ABSTRACT FROM AUTHOR]

The treatment of metastatic melanoma has been revolutionised by immunotherapy, yet a significant number of patients do not respond, and many experience autoimmune adverse events. Associations have been reported between patient outcome and monocyte subsets, whereas vitamin C (ascorbate) has been shown to mediate changes in cancer-stimulated monocytes in vitro. We therefore investigated the relationship of ascorbate with monocyte subsets and epigenetic modifications in patients with metastatic melanoma receiving immunotherapy. Patients receiving immunotherapy were compared to other cancer cohorts and age-matched healthy controls. Ascorbate levels in plasma and peripheral blood-derived mononuclear cells (PBMCs), monocyte subtype and epigenetic markers were measured, and adverse events, tumour response and survival were recorded. A quarter of the immunotherapy cohort had hypovitaminosis C, with plasma and PBMC ascorbate levels significantly lower than those from other cancer patients or healthy controls. PBMCs from the immunotherapy cohort contained similar frequencies of non-classical and classical monocytes. DNA methylation markers and intracellular ascorbate concentration were correlated with monocyte subset frequency in healthy controls, but correlation was lost in immunotherapy patients. No associations between ascorbate status and immune-related adverse events or tumour response or overall survival were apparent. [ABSTRACT FROM AUTHOR]

Main conclusion: Silicon application mitigates phosphate deficiency in barley through an interplay with auxin and nitric oxide, enhancing growth, photosynthesis, and redox balance, highlighting the potential of silicon as a fertilizer for overcoming nutritional stresses. Silicon (Si) is reported to attenuate nutritional stresses in plants, but studies on the effect of Si application to plants grown under phosphate (Pi) deficiency are still very scarce, especially in barley. Therefore, the present work was undertaken to investigate the potential role of Si in mitigating the adverse impacts of Pi deficiency in barley Hordeum vulgare L. (var. BH902). Further, the involvement of two key regulatory signaling molecules––auxin and nitric oxide (NO)––in Si-induced tolerance against Pi deficiency in barley was tested. Morphological attributes, photosynthetic parameters, oxidative stress markers (O2·−, H2O2, and MDA), antioxidant system (enzymatic––APX, CAT, SOD, GR, DHAR, MDHAR as well as non-enzymatic––AsA and GSH), NO content, and proline metabolism were the key traits that were assessed under different treatments. The P deficiency distinctly declined growth of barley seedlings, which was due to enhancement in oxidative stress leading to inhibition of photosynthesis. These results were also in parallel with an enhancement in antioxidant activity, particularly SOD and CAT, and endogenous proline level and its biosynthetic enzyme (P5CS). The addition of Si exhibited beneficial effects on barley plants grown in Pi-deficient medium as reflected in increased growth, photosynthetic activity, and redox balance through the regulation of antioxidant machinery particularly ascorbate–glutathione cycle. We noticed that auxin and NO were also found to be independently participating in Si-mediated improvement of growth and other parameters in barley roots under Pi deficiency. Data of gene expression analysis for PHOSPHATE TRANSPORTER1 (HvPHT1) indicate that Si helps in increasing Pi uptake as per the need of Pi-deficient barley seedlings, and also auxin and NO both appear to help Si in accomplishing this task probably by inducing lateral root formation. These results are suggestive of possible application of Si as a fertilizer to correct the negative effects of nutritional stresses in plants. Further research at genetic level to understand Si-induced mechanisms for mitigating Pi deficiency can be helpful in the development of new varieties with improved tolerance against Pi deficiency, especially for cultivation in areas with Pi-deficient soils. [ABSTRACT FROM AUTHOR]

A role for l -ascorbate as the precursor of several plant compounds adds to its already broad metabolic utility. There are many examples of plant species in which oxalate and l -threonate are formed from l -ascorbate breakdown, and a number of roles have been proposed for this: structural, physiological, and biochemical. On the other hand, the synthesis of l -tartrate from l -ascorbate remains limited to a very few species, amongst which we must be grateful to count the domesticated grapevine Vitis vinifera and its relatives on which wine production is based. Pathways for the degradation of ascorbate were first proposed ~50 years ago and have formed the basis of more recent biochemical and molecular analyses. The present review seeks to summarize some of these findings and to propose opportunities for future research. [ABSTRACT FROM AUTHOR]

Ascorbate is involved in numerous vital processes, in particular in response to abiotic but also biotic stresses whose frequency and amplitude increase with climate change. Ascorbate levels vary greatly depending on species, tissues, or stages of development, but also in response to stress. Since its discovery, the ascorbate biosynthetic pathway has been intensely studied and it appears that GDP- l -galactose phosphorylase (GGP) is the enzyme with the greatest role in the control of ascorbate biosynthesis. Like other enzymes of this pathway, its expression is induced by various environmental and also developmental factors. Although mRNAs encoding it are among the most abundant in the transcriptome, the protein is only present in very small quantities. In fact, GGP translation is repressed by a negative feedback mechanism involving a small open reading frame located upstream of the coding sequence (uORF). Moreover, its activity is inhibited by a PAS/LOV type photoreceptor, the action of which is counteracted by blue light. Consequently, this multi-level regulation of GGP would allow fine control of ascorbate synthesis. Indeed, experiments varying the expression of GGP have shown that it plays a central role in response to stress. This new understanding will be useful for developing varieties adapted to future environmental conditions. [ABSTRACT FROM AUTHOR]

Plants accumulate high concentrations of ascorbate, commonly in their leaves, as a redox buffer. While ascorbate levels have increased during plant evolution, the mechanisms behind this phenomenon are unclear. Moreover, has the increase in ascorbate concentration been achieved without imposing any detrimental effects on the plants? In this review, we focus on potential transitions in two regulatory mechanisms related to ascorbate biosynthesis and the availability of cellular dehydroascorbate (DHA) during plant evolution. The first transition might be that the trigger for the transcriptional induction of VTC2 , which encodes the rate-limiting enzyme in ascorbate biosynthesis, has shifted from oxidative stress (in green algae) to light/photosynthesis (in land plants), probably enabling the continuous accumulation of ascorbate under illumination. This could serve as a preventive system against the unpredictable occurrence of oxidative stress. The second transition might be that DHA-degrading enzymes, which protect cells from the highly reactive DHA in green algae and mosses, have been lost in ferns or flowering plants. Instead, flowering plants may have increased glutathione concentrations to reinforce the DHA reduction capacity, possibly allowing ascorbate accumulation and avoiding the toxicity of DHA. These potential transitions may have contributed to strategies for plants' safe and effective accumulation of ascorbate. [ABSTRACT FROM AUTHOR]

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Ascorbate (vitamin C) is an essential vitamin for the human body and participates in various physiological processes as an important coenzyme and antioxidant. Furthermore, the role of ascorbate in the prevention and treatment of cancer including gynecological cancer has gained much more interest recently. The bioavailability and certain biological functions of ascorbate are distinct in males versus females due to differences in lean body mass, sex hormones, and lifestyle factors. Despite epidemiological evidence that ascorbate-rich foods and ascorbate plasma concentrations are inversely related to cancer risk, ascorbate has not demonstrated a significant protective effect in patients with gynecological cancers. Adequate ascorbate intake may have the potential to reduce the risk of human papillomavirus (HPV) infection and high-risk HPV persistence status. High-dose ascorbate exerts antitumor activity and synergizes with chemotherapeutic agents in preclinical cancer models of gynecological cancer. In this review, we provide evidence for the biological activity of ascorbate in females and discuss the potential role of ascorbate in the prevention and treatment of ovarian, endometrial, and cervical cancers. [ABSTRACT FROM AUTHOR]

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.

The most important part of the plant antioxidant system is the ascorbate-glutathione cycle (AGC), the activity of which is observed upon exposure to a range of stressors, including lack of O2, and oxidative stress occurring immediately after the restoration of oxygen access, hereafter termed reaeration or post-anoxia. The operation of the AGC (enzymes and low-molecular components) in wheat (Triticum aestivum, cv. Leningradka, non-resistant to hypoxia) and rice (Oryza sativa, cv. Liman, resistant) seedlings after 24 h anoxia and 1 h or 24 h reaeration was studied. Significant accumulation of oxidized forms of ascorbate and glutathione was revealed in the non-resistant plant (wheat) after 24 h of anoxia and reaeration, indicating the development of oxidative stress. In the resistant plant (rice), reduced forms of these antioxidants prevailed both in normoxia and under stress, which may indicate their intensive reduction. In wheat, the activities of ascorbate peroxidase and dehydroascorbate reductase in shoots, and monodehydroascorbate reductase and glutathione reductase in roots decreased under anoxia and reaeration. The activity of antioxidant enzymes was maintained in rice under lack of oxygen (ascorbate peroxidase, glutathione reductase) and increased during post-anoxia (AGC reductases). Anoxia stimulated accumulation of mRNA of the organellar ascorbate peroxidase genes OsAPX3, OsAPX5 in shoots, and OsAPX3-5 and OsAPX7 in roots. At post-anoxia, the contribution of the OsAPX1 and OsAPX2 genes encoding the cytosolic forms of the enzyme increased in the whole plant, and so did that of the OsAPX8 gene for the plastid form of the enzyme. The accumulation of mRNA of the genes OsMDAR2 and OsMDAR4 encoding peroxisomal and cytosolic monodehydroascorbate reductase as well as the OsGR2 and OsGR3 for cytosolic and organellar glutathione reductase was activated during reaeration in shoots and roots. In most cases, O2 deficiency activated the genes encoding the peroxisomal, plastid, and mitochondrial forms of the enzymes, and upon reaeration, an enhanced activity of the genes encoding the cytoplasmic forms was observed. Taken together, the inactivation of AGC enzymes was revealed in wheat seedlings during anoxia and subsequent reaeration, which disrupted the effective operation of the cycle and triggered the accumulation of oxidized forms of ascorbate and glutathione. In rice, anoxia led to the maintenance of the activity of AGC enzymes, and reaeration stimulated it, including at the level of gene expression, which ensured the effective operation of AGC.

Drought is an abiotic disturbance that reduces photosynthesis, plant growth, and crop yield. Ascorbic acid (AsA) was utilized as a seed preconditioning agent to assist broccoli (Brassica oleracea var. italica) in resisting drought. However, the precise mechanism by which AsA improves seedlings’ development remains unknown. One hypothesis is that AsA works via antioxidant mechanisms and reduces oxidative stress. This study aims to confirm the effect of varied concentrations of AsA (control, 0 ppm, 1 ppm, or 10 ppm) on seedling growth and changes in the antioxidant status of broccoli seedlings under regular watering or drought stress. AsA increased shoot dry mass, leaf area, net photosynthesis, and water use efficiency in watered and drought-stressed seedlings. AsA significantly (p < 0.001) increased carotenoid content in watered and drought-stressed seedlings by approximately 27% and 111%, respectively. Drought increased chlorophyll b, flavonoids, phenolics, ascorbate, and hydrogen peroxide production in control seedlings, but either had no effect or less effect on plants preconditioned with 10 ppm AsA. There was no improvement in reactive oxygen species scavenging in AsA-preconditioned seedlings compared to the control. The absence or reduction in biochemical indicators of stress suggests that preconditioned broccoli seedlings do not perceive stress the same as control seedlings. In conclusion, the consistent increase in carotenoid concentration suggests that carotenoids play some role in the preconditioning response, though the exact mechanism remains unknown.

Uterine serous carcinoma is a highly aggressive non-endometrioid subtype of endometrial cancer with poor survival rates overall, creating a strong need for new therapeutic strategies to improve outcomes. High-dose ascorbate (vitamin C) has been shown to inhibit cell proliferation and tumor growth in multiple preclinical models and has shown promising anti-tumor activity in combination with chemotherapy, with a favorable safety profile. We aimed to study the anti-tumor effects of ascorbate and its synergistic effect with carboplatin on uterine serous carcinoma cells. Cell proliferation was evaluated by MTT and colony formation assays in ARK1, ARK2 and SPEC2 cells. Cellular stress, antioxidant ability, cleaved caspase 3 activity and adhesion were measured by ELISA assays. Cell cycle was detected by Cellometer. Invasion was measured using a wound healing assay. Changes in protein expression were determined by Western immunoblotting. High-dose ascorbate significantly inhibited cell proliferation, caused cell cycle arrest, induced cellular stress, and apoptosis, increased DNA damage, and suppressed cell invasion in ARK1 and SPEC2 cells. Treatment of both cells with 1 mM N -acetylcysteine reversed ascorbate-induced apoptosis and inhibition of cell proliferation. The combination of ascorbate and carboplatin produced significant synergistic effects in inhibiting cell proliferation and invasion, inducing cellular stress, causing DNA damage, and enhancing cleaved caspase 3 levels compared to each compound alone in both cells. Ascorbate has potent antitumor activity and acts synergistically with carboplatin through its pro-oxidant effects. Clinical trials of ascorbate combined with carboplatin as adjuvant treatment of uterine serous carcinoma are worth exploring. • High-dose ascorbate exhibits antiproliferative activity in uterine serous carcinoma cells through its pro-oxidant activity. • High-dose ascorbate effectively reduces adhesive and invasive abilities in uterine serous carcinoma cells. • High-dose ascorbate synergistically increases the sensitivity to carboplatin in uterine serous carcinoma cells. [ABSTRACT FROM AUTHOR]

Vitamin C, also known as ascorbic acid, is an essential nutrient that plays a critical role in many physiological processes in plants and animals. In humans, vitamin C is an antioxidant, reducing agent, and cofactor in diverse chemical processes. The established role of vitamin C as an antioxidant in plants is well recognized. It neutralizes reactive oxygen species (ROS) that can cause damage to cells. Also, it plays an important role in recycling other antioxidants, such as vitamin E, which helps maintain the overall balance of the plant's antioxidant system. However, unlike plants, humans cannot synthesize ascorbic acid or vitamin C in their bodies due to the absence of an enzyme called gulonolactone oxidase. This is why humans need to obtain vitamin C through their diet. Different fruits and vegetables contain varying levels of vitamin C. The biosynthesis of vitamin C in plants occurs primarily in the chloroplasts and the endoplasmic reticulum (ER). The biosynthesis of vitamin C is a complex process regulated by various factors such as light, temperature, and plant hormones. Recent research has identified several key genes that regulate vitamin C biosynthesis, including the GLDH and GLDH genes. The expression of these genes is known to be regulated by various factors such as light, temperature, and plant hormones. Recent studies highlight vitamin C's crucial role in regulating plant stress response pathways, encompassing drought, high salinity, and oxidative stress. The key enzymes in vitamin C biosynthesis are L-galactose dehydrogenase (GLDH) and L-galactono-1, 4-lactone dehydrogenase (GLDH). Genetic studies reveal key genes like GLDH and GLDH in Vitamin C biosynthesis, offering potential for crop improvement. Genetic variations influence nutritional content through their impact on vitamin C levels. Investigating the roles of genes in stress responses provides insights for developing resilient techniques in crop growth. Some fruits and vegetables, such as oranges, lemons, and grapefruits, along with strawberries and kiwi, are rich in vitamin C. Guava. Papaya provides a boost of vitamin C and dietary fiber. At the same time, red and yellow bell peppers, broccoli, pineapple, mangoes, and kale are additional sources of this essential nutrient, promoting overall health. In this review, we will discuss a brief history of Vitamin C and its signaling and biosynthesis pathway and summarize the regulation of its content in various fruits and vegetables. [ABSTRACT FROM AUTHOR]

Elevated genomic instability in cancer cells suggests a possible model-scenario for their selective killing via the therapeutic delivery of well-defined levels of further DNA damage. To examine this scenario, this study investigated the potential for redox modulation of oxidatively-induced DNA damage by ascorbate in malignant melanoma (MM) cancer cells, to selectively enhance both DNA damage and MM cell killing. DNA damage was assessed by Comet and ɣH2AX assays, intracellular oxidising species by dichlorofluorescein fluorescence, a key antioxidant enzymatic defence by assessment of catalase activity and cell survival was determined by clonogenic assay. Comet revealed that MM cells had higher endogenous DNA damage levels than normal keratinocytes (HaCaT cells); this correlated MM cells having higher intracellular oxidising species and lower catalase activity, and ranked with MM cell melanin pigmentation. Comet also showed MM cells more sensitive towards the DNA damaging effects of exogenous H 2 O 2 , and that ascorbate further enhanced this H 2 O 2 -induced damage in MM cells; again, with MM cell sensitivity to induced damage ranking with degree of cell pigmentation. Furthermore, cell survival data indicated that ascorbate enhanced H 2 O 2 -induced clonogenic cell death selectively in MM cells whilst protecting HaCaT cells. Finally, we show that ascorbate serves to enhance the oxidising effects of the MM therapeutic drug Elesclomol in both established MM cells in vitro and primary cell cultures ex vivo. Together, these results suggest that ascorbate selectively enhances DNA damage and cell-killing in MM cells. This raises the option of incorporating ascorbate into clinical oxidative therapies to treat MM. [Display omitted] • Malignant melanoma cells, MM: elevated oxidising species & endogenous DNA damage. • Levels of oxidising species and DNA damage correlate with MM cellular pigmentation. • Ascorbate enhances the generation of oxidatively induced DNA damage in MM. • Ascorbate leads to the selective killing of MM cells. • Ascorbate enhances the oxidising effects of Elesclomol in both in vitro and ex vivo. [ABSTRACT FROM AUTHOR]

Vitamin C is one of the most well-known and most frequently used substances found in various pharmaceutical preparations. Patients consider it a safe compound with multidirectional beneficial effects, while chemists have been presenting various possibilities for its determination for many years. The aim of this review is to present the current range of drugs and dietary supplements containing vitamin C available in Poland, divided into appropriate categories, taking into account doses, forms, and other ingredients. The second goal is to summarize the main analytical methods for determining the content of ascorbic acid. A review of the available preparations showed disproportions between a small group of drugs and a very large group of dietary supplements, which turned out to be significantly diversified in various aspects. In turn, the review of analytical methods clearly indicates the dominant share of spectroscopic ones and the fact that researchers focus primarily on improving basic, commonly known techniques. [ABSTRACT FROM AUTHOR]

The toxicity of ionizing radiation limits its effectiveness in the treatment of pancreatic ductal adenocarcinoma. Pharmacologic ascorbate (P-AscH−) has been shown to radiosensitize pancreatic cancer cells while simultaneously radioprotecting normal cells. We hypothesize that P-AscH− protects the small intestine while radiosensitizing pancreatic cancer cells partially through an oxidative stress mechanism. Duodenal samples from pancreaticoduodenectomy specimens of patients who underwent radio-chemotherapy ± P-AscH− and mouse tumor and jejunal samples treated with radiation ± P-AscH− were evaluated. Pancreatic cancer and non-tumorigenic cells were treated with radiation ± P-AscH− to assess lipid peroxidation. To determine the mechanism, pancreatic cancer cells were treated with selenomethionine or RSL3, an inhibitor of glutathione peroxidase 4 (GPx4). Radiation-induced decreases in villi length and increases in 4-HNE immunofluorescence were reversed with P-AscH− in human duodenum. In vivo, radiation-induced decreases in villi length and increased collagen deposition were reversed in P-AscH−-treated jejunal samples. P-AscH− and radiation increased BODIPY oxidation in pancreatic cancer cells but not in non-tumorigenic cells. Selenomethionine increased GPx4 protein and activity in pancreatic cancer and reversed P-AscH−-induced toxicity and lipid peroxidation. RSL3 treatment inhibited GPx4 activity and increased lipid peroxidation. Differences in oxidative stress may play a role in radioprotecting normal cells while radiosensitizing pancreatic cancer cells when treated with P-AscH−. [ABSTRACT FROM AUTHOR]

Currently, there is an increasing presence of heavy metals and metalloids in soils and water due to anthropogenic activities. However, the biggest problem caused by this increase is the difficulty in recycling these elements and their high permanence in soils. There are plants with great capacity to assimilate these elements or make them less accessible to other organisms. We analyzed the behavior of Solanum lycopersicum L., a crop with great agronomic interest, under the stress caused by antimony (Sb). We evaluated the antioxidant response throughout different exposure times to the metalloid. Our results showed that the enzymes involved in the AsA-GSH cycle show changes in their expression level under the stress caused by Sb but could not find a relationship between the NITROSOGLUTATHIONE REDUCTASE (GSNOR) expression data and nitric oxide (NO) content in tomato roots exposed to Sb. We hypothesize that a better understanding of how these enzymes work could be key to develop more tolerant varieties to this kind of abiotic stress and could explain a greater or lesser phytoremediation capacity. Moreover, we deepened our knowledge about Glutathione S-transferase (GST) and Glutathione Reductase (GR) due to their involvement in the elimination of the xenobiotic component. [ABSTRACT FROM AUTHOR]

Introduction and aimThe aim of this systematic review was to assess the role of vitamin C in the prevention of pancreatic cancer (PC).MethodsA comprehensive literature search was performed in PubMed, Embase and Web of Science up to August 2023, to identify randomized controlled trials (RCT), cohort studies and mendelian randomization studies based on prospective databases assessing the role of vitamin C in PC prevention.ResultsA total of twelve studies including European and North-American participants were included: two RCT, three mendelian randomization (MR) studies and seven cohort studies. Both RCT showed high quality in Cochrane risk of bias tool. Only one cohort study had

Flood events are likely to increase in the near future and are one of the events most threatening to agricultural production. Barley is the fourth most important crop and the cereal most sensitive to excessive moisture stress. Improving the stress tolerance of crops to a variety of stress factors caused by a more volatile climate is an important task for the coming years. The aim of this study was to investigate the efficacy of cold atmospheric plasma-treated water (PTW) as a foliar spray to stimulate the antioxidant system of Hordeum vulgare and thereby improve plant stress tolerance. For this purpose, we analysed the components of the ascorbate-glutathione cycle in barley leaves and roots without stress and under waterlogging conditions. PTW increased the content of total and reduced ascorbate in leaves as well as the content of reduced ascorbate in roots four weeks after treatment. This was observed both, under stress free conditions and after waterlogging and re-aeration. In leaves, enzyme activities also increased after re-aeration, and in roots, total and reduced glutathione levels increased after waterlogging compared to the control. The accumulation of low molecular weight antioxidants may increase tolerance to a variety of stress factors through more efficient scavenging of ROS. Overall, treatment of plants with PTW may trigger an adaptive response that leads to mitigation of the negative effects of stress, and thus, could be used as a priming agent for protection against subsequent more severe stress factors that occur in the plants' natural environment.

The excessive and uncontrolled use of pyrethroids, such as cypermethrin (CP), for pest control in Nigeria could adversely affect humans. This study aimed to investigate the oxidative stress response to cypermethrin exposure, focusing on measuring the parameters (i.e., malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT)) and the potential therapeutic effects of single and co-administration of ascorbate and alpha-tocopherol. The lungs and hearts of the animals were histologically examined for cypermethrin-induced cytopathic changes. Twenty-five adult male Wistar rats weighing 180–200 g were randomly assigned to five groups, each consisting of five animals. Group I was the control group that was not subjected to any treatment. Group II was orally exposed to cypermethrin at a dosage of 10 mg/kg bw without any additional treatment. Groups III, IV, and V received cypermethrin at standard doses of 10 mg/kg bw and were orally administered with ascorbate (5,000 mg/kg bw), alpha-tocopherol (3,000 mg/kg bw), and a co-administration of ascorbate (5,000 mg/kg bw) and alpha-tocopherol (3,000 mg/kg bw), respectively. The animals were euthanized after 28 days, and samples were processed for histological analysis using hematoxylin and eosin staining. Analysis of variance (ANOVA) and Duncan's multiple range test were used to compare categorical variables of the biochemical parameters and determine the levels of MDA, SOD, GPx, and CAT. The data analysis revealed that the cypermethrin-exposed, untreated rats had elevated MDA levels and a concurrently marked decrease in SOD, GPx, and CAT activities (p