Ascorbic acid modulates immune responses through Jumonji‐C domain containing histone demethylases and Ten eleven translocation (TET) methylcytosine dioxygenase

Maity, Jeet; Majumder, Satyabrata; Pal, Ranjana; Saha, Bhaskar; Mukhopadhyay, Prabir Kumar

doi:10.1002/bies.202300035

Cited by 7 publications

(3 citation statements)

References 166 publications

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“…Therefore, it is currently believed that the antitumor mechanism of ascorbate mainly utilizes its pro-oxidative activity rather than antioxidative activity in most cancer cells [70]. The characteristic of ascorbate as a cofactor for oxygenases also makes ascorbate take part in genetic and epigenetic regulation to affect cell survival [79,80]. The protective effect of ascorbate in normal cells is likely due to the low levels of redox-active labile metals and high levels of antioxidant enzymes including catalase and glutathione peroxidase to eliminate the effect of H 2 O 2 [13,81].…”

Section: Ascorbate In Gynecological Cancersmentioning

confidence: 99%

Review of the Potential Role of Ascorbate in the Prevention and Treatment of Gynecological Cancers

Shen,

Wang,

Deng

et al. 2024

Antioxidants

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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.

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Section: Ascorbate In Gynecological Cancersmentioning

confidence: 99%

Review of the Potential Role of Ascorbate in the Prevention and Treatment of Gynecological Cancers

Shen,

Wang,

Deng

et al. 2024

Antioxidants

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“…In view of its numerous molecular effects, it is not surprising that VitC modulates multiple pathways of immune cell activation and differentiation as recently reviewed in several excellent reviews [18,31,32,33]. A simplified overview is presented in Fig.…”

Section: Immune Modulation By Vitcmentioning

confidence: 99%

Empowering γδ T‐cell functionality with vitamin C

Kabelitz,

Cierna,

Juraske

et al. 2024

Eur J Immunol

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Vitamin C (ascorbic acid) is a potent antioxidant and a cofactor for various enzymes including histone demethylases and methylcytosine dioxygenases. Vitamin C also exerts direct cytotoxicity toward selected tumor cells including colorectal carcinoma. Moreover, vitamin C has been shown to impact immune cell differentiation at various levels including maturation and/or functionality of T cells and their progenitors, dendritic cells, B cells, and NK cells. γδ T cells have recently attracted great interest as effector cells for cell‐based cancer immunotherapy, due to their HLA‐independent recognition of a large variety of tumor cells. While γδ T cells can thus be also applied as an allogeneic off‐the‐shelf product, it is obvious that the effector function of γδ T cells needs to be optimized to ensure the best possible clinical efficacy. Here we review the immunomodulatory mechanisms of vitamin C with a special focus on how vitamin C enhances the effector function of γδ T cells. We also discuss future directions of how vitamin C can be used in the clinical setting to boost the efficacy of adoptive cell therapies.

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“…Regarding the immune system, AA is a powerful first-line antioxidant with multifaceted roles. For example, it regulates the function of both innate and adaptive immune cells ( 27 ). It improves plasma cell differentiation by altering epigenetic patterns ( 28 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of immune cells on ischemic stroke and the mediating roles of metabolites

Hu,

Zhou,

Zhao

et al. 2024

Front. Neurol.

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ObjectivePrevious studies have not shown an association between IgD-CD24-B-cell absolute count (IgD-CD24-AC) and ischemic stroke (IS). Our study aimed to assess the causal effect of IgD-CD24-AC on IS and to explore the role of ascorbic acid 2-sulfate (AA2S) as a potential mediator.MethodsOur study was based on the largest available genome-wide association study (GWAS). Inverse variance weighting (IVW), MR–Egger, weighted median (WMN), simple mode, and weighted mode methods were used to assess causal effects, with IVW as the primary outcome. Subsequently, we further performed a two-step MR analysis to evaluate whether AA2S mediated this causal effect. In addition, several sensitivity analyses were conducted to evaluate heterogeneity, including Cochran’s Q test, the MR–Egger intercept test, the MR-PRESSO global test, and the leave-one-out analysis.ResultsUsing the IVW approach, the risk ratio of IgD-CD24-AC to IS was estimated to be 1.216 (95% CI = 1.079–1.371, p = 0.001). This result was supported by the WMN method (OR = 1.204, 95% CI = 1.020–1.421, p = 0.028) and the MR–Egger method (OR = 1.177, 95% CI = 0.962–1.442, p = 0.133). We also observed the same trend with the simple model and weighted model. Furthermore, the proportion of genetically predicted IgD-CD24-AC mediated through AA2S levels was 3.73%.ConclusionOur study revealed a causal relationship between IgD-CD24-AC and IS, a small part of which was mediated by AA2S. These findings offer critical insights for developing immune-targeted therapies in the future and lay a strong foundation for advancements in precision medicine.

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Ascorbic acid modulates immune responses through Jumonji‐C domain containing histone demethylases and Ten eleven translocation (TET) methylcytosine dioxygenase

Cited by 7 publications

References 166 publications

Review of the Potential Role of Ascorbate in the Prevention and Treatment of Gynecological Cancers

Review of the Potential Role of Ascorbate in the Prevention and Treatment of Gynecological Cancers

Empowering γδ T‐cell functionality with vitamin C

Effects of immune cells on ischemic stroke and the mediating roles of metabolites

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