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vitamin c and skin health

Vitamin C in Most cancers and Infectious Ailments: Physiological, Biochemical and Therapeutic Interventions

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The Physiology of Vitamin C in Pores and skin

Vitamin C (ascorbic acid, ascorbate) is a straightforward low-molecular-weight carbohydrate that’s important for the physique as a water-soluble vitamin (Lykkesfeldt et al., 2014). As an antioxidant, vitamin C has each oxidized and diminished kinds within the physique: L-dehydroascorbic and L-ascorbic acid. Though vitamin C is a crucial antioxidant, people and different primates get hold of vitamin C solely from their food plan, as a result of they haven’t any skill to synthesize it. With blood circulation to all tissues and organs, plasma ascorbate acid concentrations can attain as much as 10–160 mM (1–15 mg/ml) after consuming a vitamin C food plan, and the superfluous vitamin will be excreted by the kidneys (Richelle et al., 2009). Nonetheless, there are massive variations within the ranges of vitamin C in varied organs; for instance, the mind, liver, and skeletal muscle have the very best whole content material, and the content material of testis and thyroid is low (Omaye et al., 1987).

The pores and skin is the most important multifunctional organ on the floor of the human physique and consists of three layers: the dermis, dermis, and subcutaneous tissue, which kinds a whole entire with rigidity and elasticity because the physique’s first line of protection towards dangerous exterior elements (Hunter, 1973). The dermis consists of keratinocytes and dendritic cells, and the stratum corneum can forestall each dangerous substances and pores and skin moisture loss and is developed from keratinocytes and its lipid matrix (Tagami, 2008); the dermis supplies diet for the pores and skin and is wealthy in blood vessels and nerve endings (Rittie and Fisher, 2015); and the connective tissue consists of collagen fibers and elastic fibers within the dermis, which maintains the stress and elasticity of the pores and skin (Carl and Enna, 1979). There’s a massive distinction within the content material of vitamin C within the layers of the pores and skin. The content material of ascorbic acid within the dermis is 425% larger than the content material within the dermis, and there’s a focus gradient of ascorbic acid within the epidermal keratinocytes (Shindo et al., 1994; Weber et al., 1999).

It’s well-known that there are two transport mechanisms for ascorbic acid within the pores and skin, and so they rely upon sodium-ascorbate cotransporter-1 (SVCT1) and sodium-ascorbate cotransporter-2 (SVCT2). Dermal fibroblasts current two high-affinity and low-affinity vitamin C transport mechanisms, which can be associated to plasma concentrations of ascorbic acid or stress situations (Butler et al., 1991), demonstrating that pores and skin vitamin C transport traits could also be related to pores and skin therapeutic, antioxidation, and antitumor results. Sodium-ascorbate cotransporters (SVCTs), particular sodium-dependent vitamin C transporters, exist in varied tissues and organs for vitamin C uptake and transport. SVCT1 is primarily liable for the transport of epidermal vitamin C, whereas SVCT2 is liable for intradermal transport, each of that are proven in Determine 1. SVCT2 in dermal cells (resembling fibroblasts) diffuses ascorbic acid transported from the plasma into the dermis, and SVCT1 within the dermis provides ascorbic acid to keratinocytes (Steiling et al., 2007). The SVCT2 transporter in fibroblasts within the dermis transports vitamin C from the blood into the cells (Steiling et al., 2007). If SVCT2 is contained in the fibroblasts, it will probably bind to Mg2+ however is in a low-affinity state. Alternatively, when SVCT2 is uncovered on the fibroblast membrane floor, it will probably bind to each Mg2+ and Ca2+ in excessive concentrations of sodium answer after which turns into a high-affinity state and binds to vitamin C (Savini et al., 2008). Vitamin C will be transported into the cell after binding to SVCT1 on the membrane of keratinocytes, and vitamin C and Na+ are reversed on the cell membrane at a 1:2 ratio after which discretely distributed in epidermal keratinocytes (Wang et al., 2000; Steiling et al., 2007; Savini et al., 2008). The expression of SVCT1 mRNA in mouse pores and skin below UVB irradiation confirmed time- and dose-dependent results, whereas the SVCT2 mRNA ranges didn’t change considerably, which appears to elucidate why the antioxidant capability of the dermis is larger than that of the dermis (Kang et al., 2007).

 

The Position of Vitamin C in Pores and skin

Vitamin C is concerned within the formation of the pores and skin barrier and collagen within the dermis and performs a physiological position within the pores and skin towards pores and skin oxidation, in antiaging of wrinkles, and in cell sign pathways of cell development and differentiation, that are associated to the prevalence and growth of assorted pores and skin illnesses (Ponec et al., 1997b). Vitamin C has a twin position of antioxidation and pro-oxidation, and this position maintains the steadiness of the 2 reactions within the physique (Kim Ok. et al., 2015). Ascorbic acid and transition metals, resembling Fe2+, produce reactive oxygen species (ROS) exterior of the cell, and excessive ranges of ROS can destroy the antioxidant protection system of most cancers cells (Ohno et al., 2009; Conner et al., 2012) as a result of the antioxidation system of tumor cells is incomplete and its steadiness is destroyed (Kim Ok. et al., 2015; Uetaki et al., 2015). Excessive ranges of Vitamin C within the cells result in oxygen-promoting reactions, which trigger DNA harm, the depletion of ATP reserves, and failure of mobile metabolism (Tian et al., 2014). Vitamin C can be concerned in resistance to UV-induced oxidative stress, inhibition of melanogenesis, and promotion of the differentiation of keratinocytes and has been used for a very long time as a medical remedy reagent. Vitamin C deficiency results in many systemic illnesses in people and causes scurvy on the earth’s navies (Carpenter, 2012).

Resistance to UV-Induced Oxidative Stress

Ultraviolet gentle, particularly UVA, is a crucial issue that induces pores and skin oxidative stress (McArdle et al., 2002). UVA radiation of the pores and skin produces pyrimidine dimers and singlet oxygen within the physique. The previous weakens the hydrogen bonding results between DNA double strands. The latter can generate all the oxygen radical cascade and results in the alteration of nucleic acids, proteins and lipids, which can induce pores and skin tumors (Lin et al., 2005; Rinnerthaler et al., 2015) There’s a refined and full antioxidant system within the pores and skin, which is used as a protection to the oxidation response induced by UV or ozone. The antioxidant system consists of two classes, together with the enzyme antioxidant system [superoxide dismutase (SOD) and catalase (CAT)] and non-enzymatic antioxidant system (vitamin C, vitamin E, and glutathione). The buildup of ROS over the vary of antioxidant defenses results in pores and skin illnesses (Godic et al., 2014). Nonetheless, vitamin C as a complement has its personal instability. Furthermore, topical vitamin C supplementation can counteract oxidative stress induced by UVA, which will be assessed in human pores and skin by the chemiluminescence methodology (Ou-Yang et al., 2004). As well as, the mRNA expression stage of matrix metalloproteinase-1 (MMP-1) is considerably elevated within the dermal fibroblast after UVA irradiation (Offord et al., 2002). Right here, vitamin C could forestall collagen degradation and inhibit the rise of MMP-1, which is the most important collagenolytic enzyme liable for collagen harm in UV-irradiated pores and skin (Offord et al., 2002; Brennan et al., 2003). Furthermore, the mixture of vitamin E, vitamin C, and ferulic acid can scale back the incidence of oxidative stress-induced tumors, and their antioxidant results are a lot better than the usage of vitamin C alone (Lin et al., 2005).

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Inhibiting Melanogenesis

The synthesis of melanin happens within the melanocytes of the basal layer of the dermis and will be transferred to keratinocytes in order that melanin is distributed all through the dermis (Kwak et al., 2015). Tyrosine and 2-hydroxyphenylalanine (L-dopa) are oxidized to melanin by tyrosinase, which is the rate-limiting enzyme in the entire course of (Bin et al., 2014). Whether or not vitamin C can inhibit melanogenesis is controversial. Most research have agreed that though it can’t kill melanocytes, vitamin C does inhibit melanogenesis; nonetheless, some investigators have demonstrated that the position of vitamin C within the inhibition of melanogenesis could be very weak and can’t inhibit tyrosinase exercise (Shimada et al., 2009; Panich et al., 2011). Moreover, the mixture of vitamin C and vitamin E inhibits melanocyte manufacturing extra considerably than vitamin C alone (Choi et al., 2010a).

Selling Differentiation of Keratinocytes

The integrity of the pores and skin barrier could also be associated to the differentiation of keratinocytes, which impacts the operate of the pores and skin barrier and causes pores and skin illnesses. Vitamin C enhances the late differentiation of keratinocytes, overcomes the differentiation-dependent oxidative stress, and maintains the integrity of all the cuticle (Ponec et al., 1997a; Savini et al., 2002), which is a crucial prerequisite for the integrity of the pores and skin barrier, making certain the operate of the pores and skin barrier and stopping pores and skin water loss, which in flip can result in pores and skin issues.

 

Vitamin C-Associated Pores and skin Ailments – “vitamin c and skin health”

The results of meals restriction on adjustments in nutrient consumption and severity of the pores and skin illness have been investigated; with ascorbate as a prodrug in varied pores and skin illnesses, medical remedy methods for how one can appropriately apply vitamin C have grow to be of curiosity to many dermatologists. Herein, we summarize the applying of vitamin C as a remedy for a wide range of pores and skin illnesses, resembling porphyria cutanea tarda (PCT), atopic dermatitis (AD), malignant melanoma, herpes zoster (HZ), and postherpetic neuralgia (PHN), in clinic in accordance with well-known ranges of proof (Desk 1).

Porphyria Cutanea Tarda

Variegate porphyria (VP) is an autosomal dominant sort of hepatic porphyria. Girls affected by VP seem with continual irritation, plasma oxidative harm and decreased protoporphyrinogen oxidase (PPOX), CAT and glutathione reductase (GR) actions that make heme precursors chronically accumulate in erythrocytes, presumably inducing mobile harm (Monteiro et al., 1989; Thunell et al., 1995; Ferrer et al., 2013). PCT is a typical sort of porphyria in people and is characterised clinically by acute and continual blistering of the pores and skin when uncovered to daylight, which normally happens within the center and late phases of the illness and causes nice struggling amongst sufferers (Patil et al., 2016). The primary position of uroporphyrin deacidification enzyme is the carboxylation of uroporphyrinogen (Sinclair et al., 1993, 1995). Cytochrome p450, particularly cytochrome P450 1A2 (CYP1A2), can catalyze the oxidation of uroporphyrins to type uroporphyrins (Sinclair et al., 1995, 1997b). PCT will be brought on by a lower in protoporphyrin decarboxylase exercise in urine and the buildup of uroporphyrin within the liver. Plasma ascorbate deficiency could also be an element that results in PCT, and a deficiency in ascorbic acid performs roles in some sufferers with PCT (Percy et al., 1975; Sinclair et al., 1997a; Anderson, 2007). Ascorbic acid as an antioxidant can inhibit the catalytic oxidation of CYP1LA2. Thus, vitamin C is an effective potential drug for the remedy of PCT. The prevalence and growth of the illness are associated to the iron content material: the better the iron load, the extra extreme the illness (Sinclair et al., 1995). Alternatively, ascorbic acid can inhibit the buildup of URO at low concentrations of iron, however the impact of ascorbic acid at excessive concentrations of iron (300–500 mg Fe/kg) is offset (Gorman et al., 2007). Ascorbic acid promotes iron absorption within the gut, which can be dangerous in sufferers with iron overload. Due to this fact, fixing for the iron inhibition of ascorbic acid is the primary drawback related to utilizing ascorbic acid as a medical remedy. Oral supplementation with vitamin E (50 mg/d) and vitamin C (150 mg/d) for six months diminished plasma oxidative harm and enhanced the erythrocyte actions of CAT and GR (Ferrer et al., 2010). Due to this fact, the usage of topical vitamin C for the development of sufferers with pores and skin signs stays to be studied.

Atopic Dermatitis

Atopic dermatitis (AD) is a continual relapsing irritation of the pores and skin related to allergic reactions. The lesions are characterised by erythematous papules with itching or scaling, affecting 15–30% of youngsters (Bieber, 2008; Kim et al., 2013; Tollefson and Bruckner, 2014). One cause that is vital is the structural or practical harm of the pores and skin barrier (Sivaranjani, 2013; Zaniboni et al., 2016). Keratinocytes and their intercellular lipids are vital parts of the human pores and skin barrier, and vitamin C can promote keratinocyte differentiation and the manufacturing of interstitial materials (Savini et al., 2002; Kim et al., 2011). As probably the most considerable lipid within the pores and skin barrier materials, ceramide is generated on the finish of keratinocyte differentiation (Uchida et al., 2001). AD sufferers lack a number of vitamins, together with vitamin A and vitamin C. A better variety of meals allergens have proven an affiliation with a rise within the variety of poor vitamins (Gorman et al., 2007). The ratio of vitamin C consumption is considerably larger in additional than three restricted teams in comparison with the non-restricted group, which demonstrates that vitamin C can enhance continual irritation and positively affect AD and that the consumption of a number of meals containing excessive ranges of vitamin C and vitamin A could also be associated to a lower within the danger of AD and bronchial asthma illnesses (Cook dinner et al., 1997; Forastiere et al., 2000; Arora et al., 2002; Lim et al., 2013; Park and Zippin, 2014). Vitamin C can stimulate ceramide manufacturing in keratinocytes and enhance total epidermal barrier operate (Kim Ok.P. et al., 2015). With will increase in medical signs of AD, vitamin C and ceramide ranges had been diminished, which demonstrated that vitamin C and ceramide ranges and the severity of AD are positively correlated (Shin et al., 2016). Though vitamin C will be an adjuvant remedy for a wide range of dermatitises, oral vitamin C nonetheless causes symmetrical AD (Assier et al., 2013).

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Malignant Melanoma

Melanoma derived from melanocytes is a sort of pores and skin tumor that’s extra malignant and happens within the pores and skin, pores and skin and mucous membrane switch and elimination of the attention choroid (Yussif et al., 2017). Vitamin C could affect the operate and amount of melanocytes, thereby lowering the synthesis of melanocytes (Kameyama et al., 1996). The antimelanogenesis impact of vitamin C is especially because of its position as a lowering agent within the varied oxidation phases of melanin formation (Choi et al., 2010b). Vitamin C can not directly inhibit the exercise of tyrosinase due to its antioxidant capability, thus lowering melanogenesis. Moreover, vitamin C may scale back the melanogenesis of melanoma cells stimulated by α-melanocyte-stimulating hormone (α-MSH) in vitro (Stojkovic-Filipovic and Kittler, 2014). Nonetheless, whether or not this has an impact within the medical remedy of melanoma has not but been decided. Furthermore, most cancers sufferers have been proven to have very low reserves of ascorbic acid, which is crucial for the structural integrity of the intercellular matrix. Degradation of the extracellular matrix correlates with the aggressiveness of tumor development and invasiveness of a most cancers. Vitamin C supplementation considerably diminished the metastasis of B16FO melanoma in Gulo knockout (KO) mice and inhibited the expansion of 4T1 breast most cancers cells in scorbutic mice (Cha et al., 2013). Surgical resection is efficient just for non-metastatic, early tumors, and there may be nonetheless not a superb healing chemotherapy for sufferers with tumor metastasis (Hill et al., 2015; Kaminska-Winciorek et al., 2015), though vitamin C has an inhibitory impact on the invasion and metastasis of melanoma (Bedogni and Powell, 2009; Miles et al., 2015). Vitamin C can scale back tumor development, invasion and metastasis of melanoma in mice by inhibiting the hypoxia inducible factor-1 alpha (HIF-1α) transcriptional exercise, which could play a key position in melanoma carcinogenesis (Cha et al., 2011; Miles et al., 2015). Posttranslational regulation of HIF-1α depends on proline hydrogenase and the inhibition of HIF hydrogenase, each of which require ascorbate as a cofactor (Cha et al., 2011). The poisonous results of vitamin C on tumor cells could also be associated to the induction of oxidative stress in cells. Nonetheless, when the antioxidation system of tumor cells is incomplete, the steadiness is destroyed, and the oxygen-promoting impact of vitamin C results in the dying of tumor cells (Kim Ok. et al., 2015; Uetaki et al., 2015). Vitamin C is commonly used as an adjunct to chemotherapy for tumors. Vitamin C may enhance 5-hydroxymethylcytosine (5hmC) content material in melanoma cells and trigger a lower in tumor-cell invasiveness and development (Gustafson et al., 2015). Thus, vitamin C will be thought to be a possible antitumor drug for the prevention of invasion and metastasis of melanoma, which weakens the tumor capsule integrity and invasiveness and reduces the diploma of malignancy.

Nonetheless, there may be nonetheless a lack of knowledge in regards to the route of administration for vitamin C, the dosage of medicine and the issues. We should always enhance consciousness of the truth that excessive concentrations of vitamin C induce apoptosis of malignant melanoma cells, whereas low concentrations promote the expansion of tumor cells (Yang et al., 2017). Nonetheless, it’s value noting that the poisonous results of vitamin C on most cancers cells are legitimate solely with intravenous administration and never in instances of oral administration (Levine et al., 2011). A rise in vitamin C ranges within the food plan of white girls elevated the chance of melanoma, additionally demonstrating that solely intravenous vitamin C elevated plasma ascorbic acid focus and that oral preparation had no impact on plasma focus (Feskanich et al., 2003; Ohno et al., 2009).

Herpes Zoster and Postherpetic Neuralgia

Herpes zoster and its sequelae, postherpetic neuralgia, are situations with important morbidity. HZ is brought on by the reactivation of latent varicella zoster virus (VZV) that lurks within the physique and classically impacts adults older than 50 years outdated (Insinga et al., 2005; Weaver, 2009). The particular medical manifestations are clustered, small blisters distributed alongside the unilateral peripheral nerves with acute neuralgia (Nair et al., 2014). PHN refers back to the persistence of neuralgia 4 weeks after the disappearance of herpes lesions and is a continual, debilitating neuropathic ache that may persist lengthy past the decision of seen cutaneous manifestations (Nalamachu and Morley-Forster, 2012; Gan et al., 2013; Marrero et al., 2017). Given the completely different pathogeneses of HZ and PHN, the signs will be divided into stimulus-induced ache and spontaneous ache. Spontaneous ache will be persistent or intermittent (paroxysmal). Stimulation-induced ache is commonly categorized as mechanical, thermal, or chemical (Chen et al., 2009). Current research have proposed that this ache is said to the participation of oxygen free radicals. Peripheral irritation stimulates nociceptors to provide oxygen free radicals. Oxygen free radicals take part within the stimulation of ache after they accumulate within the physique (Kim et al., 2004). Vitamin C, as an oxidant, has been reported to have a medical analgesic impact (Carr and McCall, 2017). As well as, the incidence of PHN in sufferers with HZ who lack plasma vitamin C has been considerably larger than the incidence in sufferers with regular plasma vitamin C ranges. When vitamin C supplementation is given to sufferers with HZ, the chance of subsequent PHN in these sufferers is vastly diminished, demonstrating that vitamin C has a preventive impact on PHN (Chen et al., 2011). A medical case report additionally mentions that intravenous injection of vitamin C instantly relieves ache in HZ sufferers and associated signs in PHN sufferers. As well as, vitamin C will be totally used as a therapeutic adjuvant for sufferers who’re proof against analgesics (Schencking et al., 2010; Byun and Jeon, 2011). Kim et al. (2016) discovered that medical administration of vitamin C supplementation can’t alleviate the instant extreme ache brought on by HZ however has a greater preventive impact on medical signs brought on by PHN (Kim et al., 2016). As well as, vitamin C instantly impacts the immune system to cut back the prospect of viral an infection within the physique (Hemilä, 2017), just like the applying of vitamin D, which may have an effect on the immune mechanisms of the human physique (Chao et al., 2015). Due to this fact, whether or not the mixed use of vitamin C and vitamin D has a superb and complete therapeutic impact on the presence of HZ or PHN remains to be a query value exploring.

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Different Ailments

Vitamin C in different dermatological illnesses is seen as an adjuvant to be used together with different medicine or for bodily remedy. It has good therapeutic potential in a wide range of dermatological illnesses, resembling pimples, allergic contact dermatitis, psoriasis, and progressive purpura, particularly when utilized in mixture with different medical medicine (Desk 2). Propionibacterium pimples (P. pimples) performs an lively pro-inflammatory position in the entire means of pimples and is concerned within the pores and skin keratinocytes and sebaceous glands of the pilosebaceous follicle, ensuing within the era of pimples (Beylot et al., 2014). The mixture of zinc and clarithromycin, together with vitamin C, has an antibacterial impact towards clarithromycin-resistant P. acnes in vitro (Iinuma et al., 2011), offering a brand new thought for the medical use of antibiotics within the remedy of pimples micro organism. Vitamin C, mixed with microneedle remedy for pimples scars, improved pores and skin hardness, smoothness, and postinflammatory pigmentation (Chawla, 2014). Vitamin C may scale back allergic reactions usually encountered in dermatology. A case report concluded that it diminished the allergic contact dermatitis brought on by hair dyes (Basketter et al., 2016). The primary part of hair dye is p-phenylenediamine. Pores and skin pretreated with vitamin C can inhibit the allergic response induced by p-phenylenediamine (Coenraads et al., 2016). Extra curiously, in an experimental examine on the position of LXR-a (liver X receptor alpha) within the pathogenesis of psoriasis, Soodgupta et al. (2014) demonstrated that ascorbic acid and atorvastatin mixed with 22-r-hydroxycholine returned feminine hormone-treated psoriatic keratinocytes to regular. Collagen is a crucial part within the connective tissue of the basement membrane and capillary vessels, and vitamin C is crucial for collagen synthesis. Though the pathogenesis of progressive pigmented purpuric dermatosis stays unclear, there are hypotheses that it’s related to elevated vascular fragility (Sardana et al., 2004). Elevated vascular fragility is related to diminished collagen in vascular connective tissue. Using a mixed remedy of aloin and vitamin C additionally has a superb impact on progressive pigmented purpuric dermatosis (Schober et al., 2014). Relating to vitamin C as an adjuvant for bodily remedy, it has been reported that oral pidotimod and vitamin C will be mixed after laser vaporization for the remedy of feminine genital herpes, which may enhance immunity and pure defenses and scale back the persistence of HPV an infection (Zervoudis et al., 2010). Supplementing sufferers with high-dose vitamin C considerably improved the remedy impact of short-term UVB irradiation remedy in sufferers with vitiligo, particularly within the UVB-irradiated pores and skin space (Don et al., 2006). Nonetheless, sufferers with renal insufficiency, deficiency in glucose 6-phosphate dehydrogenase or paroxysmal nocturnal hemoglobinuria shouldn’t use vitamin C as a result of vitamin C may cause poisoning (Padayatty et al., 2010).

 

Conclusion

In conclusion, dietary methods recommend the potential advantages of a food plan wealthy in vitamin C as a preventive software for sufferers with pores and skin illnesses. Vitamin C has low toxicity, is simple to acquire, and has a low worth. Due to this fact, if it may be utilized to medical remedy in dermatology, the prospects ought to be very spectacular. Notably, vitamin C supplementation modulated inflammatory cytokine secretion, decreased metastasis of melanoma, diminished tumor development and enhanced the encapsulation of tumors ensuing from a breast most cancers problem. Following these research, investigation into the impression of extreme meals limitations on development, malnutrition, and pores and skin illness administration is required, and additional research ought to examine the extensive and efficient therapeutic potential of vitamin C in dermatology. Though ascorbate supplementation in most cancers sufferers has been proposed to reverse their scorbutic signs and deal with their most cancers, dermatologists ought to take into accounts the potential dangers of the medical use of vitamin C to reduce the chance of remedy. As well as, the route of administration for the usage of vitamin C ought to obtain extra consideration. It’s obligatory to extend the focus of vitamin C in peripheral blood intravenously to be poisonous to tumor cells. Since vitamin C is a water-soluble molecule and its transdermal absorption effectivity is low, it could be of nice significance to establish environment friendly transdermal drug supply strategies for the stabilization of lively compounds, resembling discovering lipophilic derivatives of vitamin C to extend the absorption by means of the dermis. Thus, the medical use of vitamin C in sufferers with pores and skin illnesses nonetheless requires warning.

 

Writer Contributions

HL contributed the conception. KW, HJ, WL, MQ, and TD analyzed the info. KW and HJ wrote the manuscript. HL and KW revised the manuscript.

 

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