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1.
Sci Total Environ ; 750: 141707, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33182172

RESUMO

Ultraviolet (UV) filters are compounds utilized in many manufacturing processes and personal care products such as sunscreen to protect against UV-radiation. These highly lipophilic compounds are emerging contaminants of concern in aquatic environments due to their previously observed potential to bioaccumulate and exert toxic effects in marine ecosystems. Currently, research into the toxic effects of UV filter contamination of freshwater ecosystems is lacking, thus the present study sought to model the effects of acute and chronic developmental exposures to UV filters avobenzone, oxybenzone and octocrylene as well as a mixture of these substances in the freshwater invertebrate, Daphnia magna, at environmentally realistic concentrations. Median 48-hour effect and lethal concentrations were determined to be in the low mg/L range, with the exception of octocrylene causing 50% immobilization near environmental concentrations. 48-hour acute developmental exposures proved to behaviourally impair daphnid phototactic response; however, recovery was observed following a 19-day post-exposure period. Although no physiological disruptions were detected in acutely exposed daphnids, delayed mortality was observed up to seven days post-exposure at 200 µg/L of avobenzone and octocrylene. 21-day chronic exposure to 7.5 µg/L octocrylene yielded complete mortality within 7 days, while sublethal chronic exposure to avobenzone increased Daphnia reproductive output and decreased metabolic rate. 2 µg/L oxybenzone induced a 25% increase in metabolic rate of adult daphnids, and otherwise caused no toxic effects at this dose. These data indicate that UV filters can exert toxic effects in freshwater invertebrates, therefore further study is required. It is clear that the most well-studied UV filter, oxybenzone, may not be the most toxic to Daphnia, as both avobenzone and octocrylene induced behavioural and physiological disruption at environmentally realistic concentrations.


Assuntos
Daphnia , Poluentes Químicos da Água , Animais , Ecossistema , Protetores Solares/toxicidade , Raios Ultravioleta/efeitos adversos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
2.
Food Chem ; 338: 127782, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32798826

RESUMO

UV-B-driven modulation of secondary metabolism in peach fruit by enhancing the biosynthesis of specific phenolic subclasses, is attracting interest among consumers. However, current literature explored the UV-B-induced metabolic changes only in peach skin subjected to direct UV-B irradiation. Accordingly, this study aimed to understand whether UV-B radiation penetrates the fruit skin and is able to induce metabolic changes also within the inner flesh. Peaches were UV-B-irradiated either 10 or 60 min, and the flesh was sampled after 24 and 36 h. Non-targeted metabolomics revealed that UV-B has a strong impact on peach flesh metabolome, determining an initial decrease after 24 h, followed by an overall increase after 36 h, particularly for terpenoids, phenylpropanoids, phytoalexins and fatty acids in the 60 min UV-B-treated samples (+150.02, +99.14, +43.79 and +25.44 log2FC, respectively). Transmittance analysis indicated that UV-B radiation does not penetrate below the skin, suggesting a possible signalling pathway between tissues.


Assuntos
Frutas/metabolismo , Frutas/efeitos da radiação , Metaboloma/efeitos da radiação , Epiderme Vegetal/efeitos da radiação , Prunus persica/metabolismo , Prunus persica/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Prunus persica/crescimento & desenvolvimento
3.
Medicine (Baltimore) ; 99(45): e23105, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157985

RESUMO

The relationship between solar ultraviolet radiation and the risk of breast cancer is conflicting. The purpose of our study was to quantitatively assess the relationship between solar ultraviolet radiation and breast cancer risk and to analyze related factors such as age and sunscreen use.Articles indexed in PubMed and Embase and published between January 2005 and March 2020 were searched for relevant keywords. The relative risk was calculated using random-effect or fixed-effect models in the meta-analysis and dose-response meta-analysis, which were conducted according to the Meta-Analyses of Observational Studies in Epidemiology reporting guidelines. Sensitivity analyses for heterogeneity and publication bias were evaluated.Six studies were eligible for inclusion in the meta-analysis, and three of these were included in the dose-response analysis. We found a correlation between exposure to solar ultraviolet radiation and breast cancer risk (relative risk: 0.70, 95% confidence interval: 0.65, 0.75). We also found a linear dose-response relationship between the exposure and breast cancer risk (relative risk: 0.86, 95% confidence interval: 0.81, 0.91) in women over 40. Not tanning and covering the limbs were associated with breast cancer risk, but sunscreen use was not.Exposure to solar ultraviolet radiation is negatively correlated with breast cancer risk, and the association is linear in women over 40. This is the first dose-response meta-analysis on the topic, and the influence of factors such as estrogen receptor status, occupational exposure, and ethnicity requires in-depth study.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/etiologia , Exposição à Radiação/efeitos adversos , Luz Solar/efeitos adversos , Raios Ultravioleta/efeitos adversos , Relação Dose-Resposta à Radiação , Feminino , Humanos , Medição de Risco
4.
J Cosmet Sci ; 71(4): 199-208, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33022204

RESUMO

Skin exposure to solar radiation can cause many adverse effects. In addition to the sun protection factor (SPF), a parameter associated with Ultraviolet B (UVB) protection, significant evidence emphasized the crucial importance of a well-balanced protection against ultraviolet A (UVA) and for some indications, against high-energy visible light. Synergy between UV filters and filter photostability together with film-forming ingredients such as polymers that ensure the homogeneous distribution of UV filters on the skin are key factors to avoid UVA- and UVB-provoked detrimental effects of solar radiation. Clinical studies mimicking real conditions of use have been performed. The results show that a well-balanced sunscreen with at least an SPF-to-UVA protection factor ratio < 3 provides the most effective protection against DNA damage, skin photoimmunosuppression, photodermatoses, and pigmentation disorders. In addition, cosmetically pleasant sunscreens allow a sufficient amount to be applied and re-applied by consumers, ensuring continuous and even coverage of the exposed skin.


Assuntos
Raios Ultravioleta , Pele , Fator de Proteção Solar , Luz Solar , Protetores Solares , Raios Ultravioleta/efeitos adversos
5.
J Cosmet Sci ; 71(4): 217-226, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33022206

RESUMO

Melanin, in people with naturally pigmented skins, offers a high level of photoprotection against the adverse molecular and clinical effects of solar ultraviolet radiation but, in contrast, has a modest inhibitory effect on vitamin D synthesis. Tanning in those with light skin offers relatively modest photoprotection. Sunscreens have the potential to offer high levels of protection in people who lack melanin. In theory, sunscreens can give protection comparable with that of deeply pigmented skin. This depends on the labeled sun protection factor (SPF) which in turn depends on how well the sunscreen is applied. In most cases, this will not achieve the desired SPF. The threshold dose for vitamin D synthesis is much lower than that for sunburn, such that vitamin D synthesis is still possible with sunscreen application.


Assuntos
Queimadura Solar , Humanos , Pigmentação , Fator de Proteção Solar , Protetores Solares/farmacologia , Raios Ultravioleta/efeitos adversos
6.
J Oleo Sci ; 69(11): 1487-1495, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33055443

RESUMO

Photoaged skin is characterized by the appearance of pigmented spots such as solar lentigos, deep wrinkles and sags, and progresses due to chronic sun exposure. Among the wavelengths of sunlight, UVA is responsible for the appearance of wrinkles and sags that originate from structural alterations in the dermis of photoaged skin such as the depletion of collagen fibers. Thus, improving and restoring collagen fibers is an effective approach to reduce skin photoaging and maintain a youthful appearance. This study was conducted to evaluate the potential of an extract of Ocimum basilicum (OC), which contains rosmarinic acid (RA), as an anti-photoaging material focusing on the capacity to restore collagen fibers that are disrupted due to intracellular oxidative stress. In spite of their relatively low capacities for chemical scavenging of reactive oxygen species (ROS), both OC and RA showed efficient removal of biological oxidative stress by reducing levels of intracellular ROS and carbonylated proteins (CPs) in fibroblasts following exposure to single or repetitive UVA irradiations. Fibroblasts irradiated with repetitive UVA as a model for chronic sun-exposed cells showed significant increases in matrix metalloproteinase-1 and decreases in type I collagen synthesis and formed reduced numbers of collagen fibers. Since both OC and RA restored the adverse phenomena caused by repetitive UVA irradiation, we conclude that OC containing RA is an effective anti-photoaging material.


Assuntos
Cinamatos/farmacologia , Colágeno/metabolismo , Colágeno/efeitos da radiação , Depsídeos/farmacologia , Derme/citologia , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Ocimum basilicum/química , Extratos Vegetais/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos , Células Cultivadas , Cinamatos/isolamento & purificação , Depsídeos/isolamento & purificação , Fibroblastos/patologia , Humanos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo , Envelhecimento da Pele/patologia
7.
Hautarzt ; 71(10): 772-785, 2020 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-32915242

RESUMO

The sun is of great importance for human health. One important reason for this is the production of vitamin D, endorphins and many other hormones by the skin due to stimulation by sunlight. Insufficient access to sunlight increases the risk for vitamin D deficiency, a pandemic which would affect more than one billion people worldwide and under which ca. 60% of the population in Germany would suffer. The skin has a unique position in vitamin D metabolism as elementary steps for vitamin D production take place here and it is furthermore a target organ for actions of vitamin D. Due to the many positive effects of the sun, a healthy balance must be found between UV protection to shield against skin cancer but also ensuring sufficient vitamin D production. For regulation of this fragile balance between photoprotection and vitamin D production, which has accompanied mankind throughout evolution, sunscreens are an integral part of the modern lifestyle, although critical reports on possible risks for their use have recently become more frequent. This article discusses the current state of knowledge on the importance of vitamin D metabolism in human skin and the use of sun creams.


Assuntos
Neoplasias Cutâneas/prevenção & controle , Luz Solar/efeitos adversos , Raios Ultravioleta/efeitos adversos , Vitamina D/uso terapêutico , Alemanha , Humanos , Protetores Solares , Terapia Ultravioleta , Deficiência de Vitamina D
8.
J Oleo Sci ; 69(9): 1117-1124, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32879199

RESUMO

4-tert-Butyl-4'-methoxydibenzoylmethane (BMDM) is widely used throughout the world as a highly effective UVA absorber that can prevent the progression of photoaging in skin. However, due to its low photostability, BMDM is also known for the disadvantage of having a reduced capability to absorb UVA during prolonged exposure to sunlight. Although many studies have been carried out to overcome this disadvantage of BMDM, little attention has been paid to how the radicals generated from BMDM during UV exposure influence the skin. Therefore, the purpose of this study was twofold: One goal was to clarify the influence of radicals on human skin using cytotoxicity as a parameter. The second was to propose a solution that could reduce the radical formation while taking photostability into consideration. Using ESR spin trapping and superoxide dismutase (SOD) treatment, the radicals produced by the UV exposure of BMDM were shown to be superoxide anion radicals (•O2-). HaCaT keratinocytes exposed to UVA in the presence of BMDM showed a significant reduction in cell viability, indicating that the radicals produced from BMDM have a harmful influence on the skin. UVA exposure coincidently led to a reduction of UVA absorbance by BMDM. Interestingly, 2-hydroxy-4-methoxybenzophenone (Benzophenone-3; BP3) reduced both the radical formation and the cytotoxicity resulting from the UVA-exposure of BMDM, while also restoring its UVA absorbance. In conclusion, the results show that BMDM and BP3 is an effective combination to reduce the influence of UVA-exposed BMDM on the skin and to prevent the loss of UVA absorbance by BMDM during UV exposure.


Assuntos
Benzofenonas/farmacologia , Chalconas/efeitos adversos , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Propiofenonas/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Luz Solar/efeitos adversos , Protetores Solares/farmacologia , Superóxidos/metabolismo , Raios Ultravioleta/efeitos adversos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Interações Medicamentosas , Estabilidade de Medicamentos , Humanos , Propiofenonas/efeitos adversos , Envelhecimento da Pele/patologia , Protetores Solares/efeitos adversos , Fatores de Tempo
9.
Appl Opt ; 59(25): 7585-7595, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32902458

RESUMO

We present evidence-based design principles for three different UV-C based decontamination systems for N95 filtering facepiece respirators (FFRs) within the context of the SARS-CoV-2 outbreak of 2019-2020. The approaches used here were created with consideration for the needs of low- and middle-income countries (LMICs) and other under-resourced facilities. As such, a particular emphasis is placed on providing cost-effective solutions that can be implemented in short order using generally available components and subsystems. We discuss three optical designs for decontamination chambers, describe experiments verifying design parameters, validate the efficacy of the decontamination for two commonly used N95 FFRs (3M, #1860 and Gerson #1730), and run mechanical and filtration tests that support FFR reuse for at least five decontamination cycles.


Assuntos
Filtros de Ar , Descontaminação/instrumentação , Desenho de Equipamento/métodos , Máscaras , Raios Ultravioleta , Filtros de Ar/microbiologia , Filtros de Ar/virologia , Reutilização de Equipamento , Umidade , Ozônio/síntese química , Ozônio/toxicidade , Temperatura , Raios Ultravioleta/efeitos adversos
10.
Adv Exp Med Biol ; 1268: 3-15, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918211

RESUMO

How to deal with the powerful rays of the sun represents a fundamental question of environmental medicine, affecting skin cancer prevention campaigns and many other aspects of public health. However, when preparing recommendations for sunlight exposure, physicians, scientists, and other health authorities are in a dilemma, because solar radiation exerts both positive and negative effects on human health. While positive effects are at least in part mediated via the UV(Ultraviolet)-B-induced cutaneous synthesis of vitamin D, negative effects include the UV-mediated photocarcinogenesis of skin cancer. During the last century, interest in the positive effects of the sun on our health increased dramatically after the introduction of the so-called vitamin D/cancer hypothesis. In the late 1930s, Peller and Stephenson reported higher rates of skin cancer but lower rates of other cancers among the US Navy personnel. Several years later, Apperly reported an association between latitude and cancer mortality rate in North America. He argued that the "relative immunity to cancer is a direct effect of sunlight". Although the hypothesis that sun exposure may be beneficial against cancer had been proposed early, these observations supporting the hypothesis were ignored for nearly 40 years, until a clear mechanism was proposed. In the 1980s, Garland and Garland published a pilot study focusing on colon cancer and suggested that the possible benefits of sun exposure could be attributed to vitamin D. Later, the proposed protective role of vitamin D was extended to many other types of cancer. Subsequent laboratory investigations supported potential anti-carcinogenic effects of vitamin D compounds. We know today that many, but not all, of the positive effects of the sun on human health are mediated by the UV-induced cutaneous synthesis of vitamin D and other photoproducts. However, because of the abovementioned dilemma, there is an ongoing controversial discussion in scientific communities and in the general population that how much sunlight is optimal for human health. This chapter summarizes the content of the third edition of "Sunlight, Vitamin D and Skin Cancer," a book specifically designed and organized to be an up-to-date review covering the most important aspects of the ongoing debate on how much sun is good for human health and how to balance between the positive and negative effects of solar and artificial UV-radiation, including lessons learned from Paleolithic models and evolution .


Assuntos
Saúde , Luz Solar , Humanos , Medição de Risco , Luz Solar/efeitos adversos , Raios Ultravioleta/efeitos adversos , Vitamina D
11.
Adv Exp Med Biol ; 1268: 143-154, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918217

RESUMO

Solar UV exposure is critical and complex in the etiology and prognosis of skin cancer, particularly cutaneous malignant melanoma. Sun exposure and one of its "derivatives," vitamin D, have been implicated in protection against mortality from melanoma. However, the relationships are inconsistent. At this time, it is not possible to make clear recommendations for or against sun exposure in relationship to melanoma prognosis. However, this relationship deserves continued exploration.


Assuntos
Neoplasias Cutâneas/mortalidade , Raios Ultravioleta , Humanos , Melanoma/etiologia , Melanoma/mortalidade , Melanoma/prevenção & controle , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/mortalidade , Neoplasias Induzidas por Radiação/prevenção & controle , Prognóstico , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/prevenção & controle , Raios Ultravioleta/efeitos adversos , Vitamina D
12.
Adv Exp Med Biol ; 1268: 195-209, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918220

RESUMO

Human papillomaviruses (HPVs) infect squamous epithelia and can induce hyperproliferative lesions. More than 220 different HPV types have been characterized and classified into five different genera. While mucosal high-risk HPVs have a well-established causal role in anogenital carcinogenesis, the biology of cutaneous HPVs is less well understood.From patients with the rare genetic disorder epidermodysplasia verruciformis (EV) and animal models, evidence is accumulating that cutaneous PV of genus ß synergize with ultraviolet (UV) radiation in the development of cutaneous squamous cell carcinoma (cSCC). In 2009, the International Agency for Research on Cancer (IARC) classified the genus ß-HPV types 5 and 8 as "possible carcinogenic" biological agents (group 2B) in EV disease. Epidemiological and biological studies indicate that genus ß-PV infection may also play a role in UV-mediated skin carcinogenesis in non-EV patients. However, they rather act at early stages of carcinogenesis and become dispensable for the maintenance of the malignant phenotype, compatible with a "hit-and-run" mechanism.This chapter will give an overview on genus ß-PV infections and discuss similarities and differences of cutaneous and genus α mucosal high-risk HPV in epithelial carcinogenesis.


Assuntos
Papillomaviridae/patogenicidade , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/virologia , Animais , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/virologia , Epidermodisplasia Verruciforme/etiologia , Epidermodisplasia Verruciforme/virologia , Humanos , Raios Ultravioleta/efeitos adversos
13.
Adv Exp Med Biol ; 1268: 227-253, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918222

RESUMO

Exposure of skin cells to UV radiation results in DNA damage, which if inadequately repaired, may cause mutations. UV-induced DNA damage and reactive oxygen and nitrogen species also cause local and systemic suppression of the adaptive immune system. Together, these changes underpin the development of skin tumours. The hormone derived from vitamin D, calcitriol (1,25-dihydroxyvitamin D3) and other related compounds, working via the vitamin D receptor and at least in part through endoplasmic reticulum protein 57 (ERp57), reduce cyclobutane pyrimidine dimers and oxidative DNA damage in keratinocytes and other skin cell types after UV. Calcitriol and related compounds enhance DNA repair in keratinocytes, in part through decreased reactive oxygen species, increased p53 expression and/or activation, increased repair proteins and increased energy availability in the cell when calcitriol is present after UV exposure. There is mitochondrial damage in keratinocytes after UV. In the presence of calcitriol, but not vehicle, glycolysis is increased after UV, along with increased energy-conserving autophagy and changes consistent with enhanced mitophagy. Reduced DNA damage and reduced ROS/RNS should help reduce UV-induced immune suppression. Reduced UV immune suppression is observed after topical treatment with calcitriol and related compounds in hairless mice. These protective effects of calcitriol and related compounds presumably contribute to the observed reduction in skin tumour formation in mice after chronic exposure to UV followed by topical post-irradiation treatment with calcitriol and some, though not all, related compounds.


Assuntos
Calcitriol/farmacologia , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos da radiação , Dano ao DNA/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos , Vitamina D/farmacologia , Animais , Calcitriol/química , Calcitriol/metabolismo , Humanos , Vitamina D/química , Vitamina D/metabolismo , Vitaminas/química , Vitaminas/metabolismo , Vitaminas/farmacologia
14.
Adv Exp Med Biol ; 1268: 285-306, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918224

RESUMO

Cutaneous malignancies including melanomas and keratinocyte carcinomas (KC) are the most common types of cancer, occurring at a rate of over one million per year in the United States. KC, which include both basal cell carcinomas and squamous cell carcinomas, are substantially more common than melanomas and form the subject of this chapter. Ultraviolet radiation (UVR), both UVB and UVA, as occurs with sunlight exposure is generally regarded as causal for these malignancies, but UVB is also required for vitamin D synthesis in the skin. Keratinocytes are the major cell in the epidermis. These cells not only produce vitamin D but contain the enzymatic machinery to metabolize vitamin D to its active metabolite, 1,25(OH)2D, and express the receptor for this metabolite, the vitamin D receptor (VDR). This allows the cell to respond to the 1,25(OH)2D that it produces. Based on our own data and that reported in the literature, we conclude that vitamin D signaling in the skin suppresses UVR-induced epidermal tumor formation. In this chapter we focus on four mechanisms by which vitamin D signaling suppresses tumor formation. They are inhibition of proliferation/stimulation of differentiation with discussion of the roles of hedgehog, Wnt/ß-catenin, and hyaluronan/CD44 pathways in mediating vitamin D regulation of proliferation/differentiation, regulation of the balance between oncogenic and tumor suppressor long noncoding RNAs, immune regulation, and promotion of DNA damage repair (DDR).


Assuntos
Receptores de Calcitriol/metabolismo , Pele/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Humanos , Queratinócitos/metabolismo , Pele/citologia , Neoplasias Cutâneas/metabolismo , Raios Ultravioleta/efeitos adversos , Vitamina D/metabolismo
15.
Adv Exp Med Biol ; 1268: 307-318, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918225

RESUMO

It has now been convincingly shown that vitamin D and p53 signaling protect against spontaneous or carcinogen-induced malignant transformation of cells. The vitamin D receptor (VDR) and the p53/p63/p73 proteins (the p53 family hereafter) exert their effects as receptors/sensors that turn into transcriptional regulators upon stimulus. While the p53 clan, mostly in the nucleoplasm, responds to a large and still growing number of alterations in cellular homeostasis commonly referred to as stress, the nuclear VDR is transcriptionally activated after binding its naturally occurring biologically active ligand 1,25-dihydroxyvitamin D with high affinity. Interestingly, a crosstalk between vitamin D and p53 signaling has been demonstrated that occurs at different levels, has genome-wide implications, and is of high importance for many malignancies, including non-melanoma skin cancer. These interactions include the ability of p53 to upregulate skin pigmentation via POMC derivatives including alpha-MSH and ACTH. Increased pigmentation protects the skin against UV-induced DNA damage and skin photocarcinogenesis, but also inhibits cutaneous synthesis of vitamin D. A second level of interaction is characterized by binding of VDR and p53 protein, an observation that may be of relevance for the ability of 1,25-dihydroxyvitamin D to increase the survival of skin cells after UV irradiation. UV irradiation-surviving cells show significant reductions in thymine dimers in the presence of 1,25-dihydroxyvitamin D that are associated with increased nuclear p53 protein expression and significantly reduced NO products. A third level of interaction is documented by the ability of vitamin D compounds to regulate the expression of the murine double minute (MDM2) gene in dependence of the presence of wild-type p53. MDM2 has a well-established role as a key negative regulator of p53 activity. Finally, p53 and its family members have been implicated in the direct regulation of the VDR. This review gives an update on some of the implications of the crosstalk between vitamin D and p53 signaling for carcinogenesis in the skin and other tissues, focusing on a genome-wide perspective.


Assuntos
Neoplasias/metabolismo , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo , Vitamina D/metabolismo , Animais , Humanos , Raios Ultravioleta/efeitos adversos , Vitaminas/metabolismo
16.
Adv Exp Med Biol ; 1268: 257-283, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918223

RESUMO

Nonmelanoma skin cancers including basal and squamous cell carcinomas (SCC and BCC) represent a significant clinical problem due to their relatively high incidence, imposing an economic burden to healthcare systems around the world. It is accepted that ultraviolet radiation (UVR: λ = 290-400 nm) plays a crucial role in the initiation and promotion of BCC and SCC with UVB (λ = 290-320 nm) having a central role in this process. On the other hand, UVB is required for vitamin D3 (D3) production in the skin, which supplies >90% of the body's requirement for this prohormone. Prolonged exposure to UVB can also generate tachysterol and lumisterol. Vitamin D3 itself and its canonical (1,25(OH)2D3) and noncanonical (CYP11A1-intitated) D3 hydroxyderivatives show photoprotective functions in the skin. These include regulation of keratinocyte proliferation and differentiation, induction of anti-oxidative responses, inhibition of DNA damage and induction of DNA repair mechanisms, and anti-inflammatory activities. Studies in animals have demonstrated that D3 hydroxyderivatives can attenuate UVB or chemically induced epidermal cancerogenesis and inhibit growth of SCC and BCC. Genomic and non-genomic mechanisms of action have been suggested. In addition, vitamin D3 itself inhibits hedgehog signaling pathways which have been implicated in many cancers. Silencing of the vitamin D receptor leads to increased propensity to develop UVB or chemically induced epidermal cancers. Other targets for vitamin D compounds include 1,25D3-MARRS, retinoic orphan receptors α and γ, aryl hydrocarbon receptor, and Wnt signaling. Most recently, photoprotective effects of lumisterol hydroxyderivatives have been identified. Clinical trials demonstrated a beneficial role of vitamin D compounds in the treatment of actinic keratosis. In summary, recent advances in vitamin D biology and pharmacology open new exciting opportunities in chemoprevention and treatment of skin cancers.


Assuntos
Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/prevenção & controle , Vitamina D/química , Animais , Progressão da Doença , Humanos , Receptores de Calcitriol/metabolismo , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/efeitos da radiação , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Raios Ultravioleta/efeitos adversos , Vitamina D/metabolismo , Vitamina D/farmacologia , Vitaminas/química , Vitaminas/metabolismo , Vitaminas/farmacologia
17.
Adv Exp Med Biol ; 1268: 355-379, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918228

RESUMO

Incidence rates of nonmelanoma skin cancer and melanoma have been on the rise in the USA for the past 25 years. UV radiation (UVR) exposure remains the most preventable environmental risk factor for these cancers. Aside from sun avoidance, sunscreens continue to provide the best alternative protection. UVR directly damages DNA and causes indirect cellular damage through the creation of reactive oxygen species, the sum of which leads to cutaneous immunosuppression and a tumorigenic milieu. The current generation of sunscreens protect from UVR through two main mechanisms: absorption and deflection. In the USA, the Food and Drug Association (FDA) regulates sunscreen products which are considered over-the-counter drugs. With the release of new FDA testing and labeling requirements in 2011 and the enactment of the Sunscreen Innovation Act in 2014, sunscreen manufacturers are now required to evaluate their products not only on the sun protection factor (SPF) but also on broad-spectrum UVA protection. The American Academy of Dermatology Association and the American Academy of Pediatrics have provided specific recommendations for proper sun protection and sunscreen usage with the continual goal of increasing public awareness and compliance with appropriate sun protective measures. Antioxidants, photolyases, and plant polyphenols remain an interesting avenue of research as additives to sunscreens or stand-alone topical or oral products that appear to modulate the immunosuppressive effects of UVR on the skin. Additionally, although UVR induces endogenous cutaneous production of vitamin D, its damaging effects overshadow this positive benefit, especially in light of the ease of achieving recommended amounts of vitamin D through diet and supplementation.


Assuntos
Protetores Solares/normas , Humanos , Incidência , Melanoma/epidemiologia , Melanoma/prevenção & controle , Medição de Risco , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/prevenção & controle , Protetores Solares/química , Raios Ultravioleta/efeitos adversos , Estados Unidos/epidemiologia , Vitamina D/administração & dosagem
18.
Adv Exp Med Biol ; 1268: 387-405, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918230

RESUMO

Exposure to sunlight is a major source of vitamin D for most people. Yet public health advice has focused overwhelmingly on avoiding exposure of unprotected skin because of the risks of erythema and skin cancer. Given that there are also health risks associated with low vitamin D status, we explore the possibilities of achieving a range of targets associated with vitamin D and the accompanying erythema risk. We have calculated the exposure required to gain a number of proposed oral-equivalent doses of vitamin D, as functions of latitude, season, skin type and skin area exposed, together with the associated risk of erythema, expressed in minimum erythema doses. The model results show that a recommended daily intake of 400 IU is readily achievable through casual sun exposure in the midday lunch hour, with no risk of erythema, for all latitudes some of the year, and for all the year at some (low) latitudes. We also show that such daily, sub-erythemal doses at lunchtime during the summer months is sufficient to avoid winter-time vitamin D deficiency for the UK all-weather climate, provided that lower arms and legs are exposed in the warmer months. At the higher proposed vitamin D dose of 1000 IU, lunchtime sun exposure is still a viable route to the vitamin but requires the commitment to expose greater areas of skin and is effective for a shorter period of the year. The highest vitamin D requirement considered was 4000 IU per day. For much of the globe and much of the year, this is not achievable in a lunchtime hour and where it is possible large areas of skin must be exposed to prevent erythema. When the only variable considered was skin type, latitudinal and seasonal limits on adequate vitamin D production were more restrictive for skin type 5 than skin type 2.


Assuntos
Eritema/etiologia , Pele/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Vitamina D/biossíntese , Humanos , Medição de Risco , Pele/patologia , Deficiência de Vitamina D/prevenção & controle
19.
Adv Exp Med Biol ; 1268: 409-419, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918231

RESUMO

The biology of every species has been optimized for life in the environment in which that species evolved. Humans originated in the tropics, and while some natural selection took place in response to behaviors and environments that decreased exposure to ultraviolet light, there has never been a species-wide biological accommodation. Paleolithic nutrition advocates argue that risk of disease is higher because modern diets differ from what was consumed by early humans. Early humans were the naked ape living in the tropics, exposed to high levels of ultraviolet light and vitamin D nutrition (serum 25-hydroxyvitamin D; 25(OH)D) averaging 115 nmol/L, as compared to today's population averages that are well below 70 nmol/L. Natural selection from an available gene pool cannot compensate fully to an environmental change away from the one within which the species originally evolved. Vitamin D nutrition remains a contentious area. The epidemiological evidence consistently relates lower 25(OH)D to higher disease risk. However, evidence from double-blind clinical trials looking at preventing new disease in healthy volunteers has been disappointing. But such negative trials have been the case for all nutrients except for folic acid which lowers risk of spina bifida. The Paleolithic nutrition model is based on fundamental biological concepts, but it has overlooked the environmental effects of ultraviolet light and vitamin D nutrition. This paper presents evolutionary and Paleolithic aspects of ultraviolet light and vitamin D with the aim to support pertinent research and, ultimately, public policy regarding nutrition and light exposure.


Assuntos
Evolução Biológica , Modelos Biológicos , Política Nutricional , Raios Ultravioleta , Vitamina D/metabolismo , Suplementos Nutricionais , Humanos , Raios Ultravioleta/efeitos adversos , Vitamina D/administração & dosagem , Vitaminas/administração & dosagem , Vitaminas/metabolismo
20.
Clin Dermatol ; 38(4): 485-488, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32972607

RESUMO

Many factors affect the health and physiology of human skin, with some of them arising from outer space. This contribution explores four celestial influences on the skin: (1) the sun's ultraviolet light, which has both beneficial and deleterious dermatologic effects, (2) meteorite injuries, (3) possible lunar effects on the body's health, and (4) cosmic radiation as a risk factor for skin cancer and pregnancy-related complications. Some of these extraterrestrial influences on skin health have taken on added significance as human beings increasingly spend more time at higher altitudes in aircraft, spaceships, and space stations.


Assuntos
Radiação Cósmica/efeitos adversos , Neoplasias Cutâneas/etiologia , Pele/lesões , Pele/efeitos da radiação , Luz Solar/efeitos adversos , Raios Ultravioleta/efeitos adversos , Aeronaves , Altitude , Dermatite de Contato/etiologia , Feminino , Humanos , Masculino , Meteoroides , Lua , Gravidez , Complicações na Gravidez/etiologia
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