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1.
Artigo em Inglês | MEDLINE | ID: mdl-33050590

RESUMO

In addition to looking for effective drugs and a vaccine, which are necessary to save and protect human health, it is also important to limit, or at least to slow, the spread of coronavirus. One important element in this action is the use of individual protective devices such as filtering facepiece masks. Currently, masks that use a mechanical filter, such as a HEPA (High Efficiency Particulate Air) filter, are often used. In some countries that do not have a well-developed healthcare system or in exceptional situations, there is a real and pressing need to restore filters for reuse. This article presents technical details for a very simple device for sterilization, including of HEPA polymer filters. The results of biological and microscopic tests confirming the effectiveness of the sterilization performed in the device are presented. The compact and portable design of the device also allows its use to disinfect other small surfaces, for example a small fragment of a floor, table, or bed.


Assuntos
Microbiologia do Ar , Infecção Hospitalar/prevenção & controle , Filtração , Máscaras , Esterilização/métodos , Raios Ultravioleta , Humanos
2.
Water Sci Technol ; 82(7): 1404-1415, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33079719

RESUMO

In this study, peroxydisulfate (PDS) was successfully activated by UV-irradiation for the degradation of paracetamol (PCT) frequently detected in the environment. Results showed that increasing the initial PDS concentration from 5 to 20 mM promote the removal of PCT from 49.3% to 97.5% after 240 min of reaction time. As the initial PCT concentration increased from 0.066 to 0.132 mM, the degradation efficiency of PCT decreased from 98% to 73% after 240 min of reaction time, while the optimal pH was found to be 6. It is apparent that the degradation rate of PCT was favored by the lamp power regardless of the initial PCT concentration, for 0.132 mM of PCT, the degradation efficiency increased from 73% to 95% when the lamp power increased from 9 to 30 W, respectively. The kinetic of degradation of the PCT was described by a pseudo-second order kinetic model. The model obtained by central composite design led to the following optimal conditions for PCT degradation: 0.132 mM initial PCT concentration, 20 mM PDS dose, pH solution 6 and lamp power 30 W led to the removal of 92% of PCT at 25 °C within 240 min of reaction time.


Assuntos
Acetaminofen , Poluentes Químicos da Água , Cinética , Sulfatos , Raios Ultravioleta , Poluentes Químicos da Água/análise
3.
Water Sci Technol ; 82(7): 1454-1466, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33079723

RESUMO

Tannins are recalcitrant polyphenolic molecules that resist microbial attack. Their main environmental damage is due to their low biodegradability. This work aims to investigate the photo-catalytic degradation of two commercial tannin extracts, chestnut (hydrolysable tannin) and mimosa (condensed tannin). The experiments were carried out under UV-light irradiation in a continuous-flow reactor using titanium dioxide (TiO2) immobilized on cellulosic fibers. It was highlighted that photo-catalytic degradation is unfavourable in acidic medium and when the pH is too high (pH above 12); it reaches its maximum efficiency at pH 7.5 (99 and 97% for chestnut and mimosa, respectively). Nearly complete degradation of tannins requires an irradiation period of 6 h. The process efficiency is inversely affected by the concentration of tannins essentially above 75 mg/L for chestnut and 60 mg/L for mimosa. Above 240 mL/min, any increase in feed flow negatively affects the performance of the process. Furthermore, a significant decrease of treatment efficiency was seen when increasing the concentration of ethanol and salts in the medium. Obtained results suggest that UV-light irradiation in a continuous-flow photo-reactor using immobilized TiO2 may be considered as an adequate process for the treatment of water containing recalcitrant tannin molecules.


Assuntos
Taninos , Titânio , Catálise , Raios Ultravioleta
4.
Vestn Oftalmol ; 136(6): 42-49, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33084278

RESUMO

PURPOSE: To perform a comparative assessment of the bactericidal and fungicidal effects of various parts of the radiation spectrum (Ultraviolet A, red, green and blue). MATERIAL AND METHODS: The study included strains of the most clinically significant microorganisms, which are the most common causes of purulent keratitis - S. aureus, P. aeruginosa and fungi C. albicans. After populating the surface of Petri dishes uniformly with microorganisms of each culture, on four out of the five specimens the central zone of the surface with a diameter of 1 cm was irradiated with light of different spectrum - from ultraviolet to red, with a total radiation energy density of 5.4 J/cm2. One specimen remained as the control subject. After irradiation, scanning electron microscopy with lanthanides contrasting (SEMLC) was used to evaluate the total metabolic activity, the activity of the efflux systems and the morphological characteristics of the microorganisms. RESULTS: The damaging effect of visible spectrum light and UVA radiation on S. aureus, P. aeruginosa and C. albicans cultures was proved by SEMLC. Green spectrum emission with a wavelength of 500 nm had the highest antimicrobial activity. It was manifested by a decrease in the overall level of metabolic activity (from 40-63 c.u. to 26-37 c.u. (S. aureus (p<0.01), P. aeruginosa (p<0.01) and C. albicans (p<0.05)), as well as a 2-fold increase in the proportion of S. aureus cells with active efflux systems. CONCLUSION: SEMLC allows evaluation of parameters of the microorganisms` state: morphological (form and size) and functional (general metabolic activity, activation of efflux systems). Investigation of S. aureus, P. aeruginosa and C. albicans cultures using SEMLC demonstrated the antimicrobial activity of green spectrum radiation of 500 nm wavelength. This will serve as a basis for further research and development of a method of treating infectious keratitis using green light.


Assuntos
Pseudomonas aeruginosa , Staphylococcus aureus , Antibacterianos , Luz , Raios Ultravioleta
5.
Virol J ; 17(1): 145, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028356

RESUMO

BACKGROUND: The rate at which COVID-19 has spread throughout the globe has been alarming. While the role of fomite transmission is not yet fully understood, precise data on the environmental stability of SARS-CoV-2 is required to determine the risks of fomite transmission from contaminated surfaces. METHODS: This study measured the survival rates of infectious SARS-CoV-2, suspended in a standard ASTM E2197 matrix, on several common surface types. All experiments were carried out in the dark, to negate any effects of UV light. Inoculated surfaces were incubated at 20 °C, 30 °C and 40 °C and sampled at various time points. RESULTS: Survival rates of SARS-CoV-2 were determined at different temperatures and D-values, Z-values and half-life were calculated. We obtained half lives of between 1.7 and 2.7 days at 20 °C, reducing to a few hours when temperature was elevated to 40 °C. With initial viral loads broadly equivalent to the highest titres excreted by infectious patients, viable virus was isolated for up to 28 days at 20 °C from common surfaces such as glass, stainless steel and both paper and polymer banknotes. Conversely, infectious virus survived less than 24 h at 40 °C on some surfaces. CONCLUSION: These findings demonstrate SARS-CoV-2 can remain infectious for significantly longer time periods than generally considered possible. These results could be used to inform improved risk mitigation procedures to prevent the fomite spread of COVID-19.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Humanos , Viabilidade Microbiana , Pandemias , Temperatura , Raios Ultravioleta , Carga Viral
6.
Glob Health Sci Pract ; 8(3): 582-595, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33008865

RESUMO

As the current COVID-19 pandemic illustrates, not all hospitals and other patient care facilities are equipped with enough personal protective equipment to meet the demand in a crisis. Health care workers around the world use filtering facepiece respirators to protect themselves and their patients, yet during this global pandemic they are forced to reuse what are intended to be single-use masks. This poses a significant risk to these health care workers along with the people they are trying to protect. Ultraviolet germicidal irradiation (UVGI) has been validated previously as a method to effectively decontaminate these masks between use. However, not all facilities have access to the expensive commercial ultraviolet type C (UV-C) lamp decontamination equipment required for UVGI. UV-C bulbs are sitting idle in biosafety cabinets at universities and research facilities around the world that have been shuttered to slow the spread of COVID-19. These bulbs may also be available in existing medical centers where infectious diseases are commonly treated. We developed a method to modify existing light fixtures or create custom light fixtures that are compatible with new or existing UV-C bulbs. This system is scalable; can be created for less than US$50, on site and at the point of need; and leverages resources that are currently untapped and sitting unused in public and private research facilities during the pandemic. The freely accessible design can be easily modified for use around the world. Health care facilities can obtain this potentially lifesaving UVGI resource with minimal funds by collaborating with research facilities to obtain the UV-C meters and UV-C bulbs if they are unavailable from other sources. Although mask reuse is not ideal, we must do what we can in emergency situations to protect our health care workers responding to the pandemic and the communities they serve.


Assuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Descontaminação/métodos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Dispositivos de Proteção Respiratória , Raios Ultravioleta , Humanos
7.
Chemosphere ; 258: 127393, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32947669

RESUMO

UV/chlorine and chlorination processes have drawn great interests of water treatment utilities for oxidation and disinfection purposes. This work proposed a restricted chlorine-dosing strategy for UV/chlorine and post-chlorination under different pH and UV irradiation conditions by comprehensively assessing the oxidation of natural organic matter (NOM), formation of 9 haloacetic acids (HAA9) and bromate, and alteration of toxicity. During UV/chlorine with restricted chlorine doses, the oxidation of NOM chromophores (i.e., ΔUVA254) showed an apparent dependence on cumulative exposures of free available chlorine (CTFAC); Meanwhile, HAA9 formation was determined by CTFAC values and could be linearly correlated with ΔUVA254 irrespective of pH and UV irradiation wavelength. Irradiated by 254 nm LP-Hg lamp, the faster chlorine photolysis produced relatively higher steady-state concentrations of Cl• and HO• species but resulted in lower CTFAC. Reducing CTFAC values by operation parameters (pH, UV wavelength and irradiation fluence) could mitigate HAA9 formation during UV/chlorine at a specific chlorine dose. Additionally, high bromide concentration and acidic pH promoted more bromo-HAAs formation, and the presence of NOM significantly suppressed bromate formation. Analogous to ozonation, the UV/chlorine pre-oxidation could reduce the HAA9 formation potentials during post-chlorination at mildly alkaline pH. The photobacterium bioassay further demonstrated that although the UV/chlorine treatment might have increased the acute toxicity, the post-chlorination treatment could polish the acute toxicity to the level of chlorination alone. These results suggest that with the restricted chlorine-dosing strategy, the trade-off between oxidation/disinfection efficiency and DBPs formation can be controlled by monitoring CTFAC and ΔUVA254 values during UV/chlorine treatment.


Assuntos
Purificação da Água/métodos , Bromatos , Brometos/efeitos da radiação , Cloro , Desinfecção , Halogenação , Concentração de Íons de Hidrogênio , Oxirredução , Fotólise , Raios Ultravioleta , Poluentes Químicos da Água/análise , Purificação da Água/normas
8.
J Nanobiotechnology ; 18(1): 130, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912236

RESUMO

Fast point-of-care (POC) diagnostics represent an unmet medical need and include applications such as lateral flow assays (LFAs) for the diagnosis of sepsis and consequences of cytokine storms and for the treatment of COVID-19 and other systemic, inflammatory events not caused by infection. Because of the complex pathophysiology of sepsis, multiple biomarkers must be analyzed to compensate for the low sensitivity and specificity of single biomarker targets. Conventional LFAs, such as gold nanoparticle dyed assays, are limited to approximately five targets-the maximum number of test lines on an assay. To increase the information obtainable from each test line, we combined green and red emitting quantum dots (QDs) as labels for C-reactive protein (CRP) and interleukin-6 (IL-6) antibodies in an optical duplex immunoassay. CdSe-QDs with sharp and tunable emission bands were used to simultaneously quantify CRP and IL-6 in a single test line, by using a single UV-light source and two suitable emission filters for readout through a widely available BioImager device. For image and data processing, a customized software tool, the MultiFlow-Shiny app was used to accelerate and simplify the readout process. The app software provides advanced tools for image processing, including assisted extraction of line intensities, advanced background correction and an easy workflow for creation and handling of experimental data in quantitative LFAs. The results generated with our MultiFlow-Shiny app were superior to those generated with the popular software ImageJ and resulted in lower detection limits. Our assay is applicable for detecting clinically relevant ranges of both target proteins and therefore may serve as a powerful tool for POC diagnosis of inflammation and infectious events.


Assuntos
Biomarcadores/análise , Proteína C-Reativa/análise , Imunoensaio/métodos , Interleucina-6/análise , Pontos Quânticos/química , Sepse/diagnóstico , Anticorpos/imunologia , Betacoronavirus/isolamento & purificação , Proteína C-Reativa/imunologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Humanos , Interleucina-6/imunologia , Limite de Detecção , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Sistemas Automatizados de Assistência Junto ao Leito , Sepse/metabolismo , Software , Raios Ultravioleta
9.
Ecotoxicol Environ Saf ; 205: 111343, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32979801

RESUMO

Taste and odor (T&O) problem in water is one of the main obstacles to improve the quality of drinking water, and efficient water treatment processes are urgently needed to control T&O compounds. Ultraviolet-mediated peroxymonosulfate (UV/PMS) diminution of trichloroanisole (TCA) in water was investigated in this paper. The treatment of 2,3,6-trichloroanisole (2,3,6-TCA) by three advanced oxidation processes (UV, UV/H2O2 and UV/PMS) was compared, and UV/PMS stood out. SO4•- and HO• were produced in the UV/PMS, and their specific contributions to 2,3,6-TCA oxidation were investigated. The competitive kinetic model was applied to determine the second-order reaction rate between 2,3,6-TCA and SO4•- or HO•. The products of 2,3,6-TCA generated in UV/PMS were analyzed with gas chromatography/high resolution-mass spectrometry (GC/HR-MS), and the degradation mechanism was proposed. The effects of water matrices (chloride, bicarbonate and humic acid) on UV/PMS performance were studied, and the decontamination of 2,3,6-TCA in real water was carried out. The disinfection byproducts (DBPs) alteration from 2,3,6-TCA by UV/PMS - chlorination treatment was explored. Overall, UV/PMS can effectively deal with the T&O pollution of TCA in water.


Assuntos
Anisóis/química , Peróxidos/química , Poluentes Químicos da Água/química , Cloro/análise , Desinfecção , Halogenação , Substâncias Húmicas/análise , Peróxido de Hidrogênio/química , Cinética , Oxirredução , Raios Ultravioleta , Água , Poluentes Químicos da Água/análise , Purificação da Água/métodos
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: 19-36, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918212

RESUMO

Vitamin D is the sunshine vitamin for good reason. During exposure to sunlight, the ultraviolet B photons enter the skin and photolyze 7-dehydrocholesterol to previtamin D3 which in turn is isomerized by the body's temperature to vitamin D3. Most humans have depended on sun for their vitamin D requirement. Skin pigment, sunscreen use, aging, time of day, season, and latitude dramatically affect previtamin D3 synthesis. Vitamin D deficiency was thought to have been conquered, but it is now recognized that more than 50% of the world's population is at risk for vitamin D deficiency. This deficiency is in part due to the inadequate fortification of foods with vitamin D and the misconception that a healthy diet contains an adequate amount of vitamin D. Vitamin D deficiency causes growth retardation and rickets in children and will precipitate and exacerbate osteopenia, osteoporosis and increase risk of fracture in adults. The vitamin D deficiency pandemic has other serious consequences including increased risk of common cancers, autoimmune diseases, infectious diseases, and cardiovascular disease. There needs to be a renewed appreciation of the beneficial effect of moderate sensible sunlight for providing all humans with their vitamin D requirement for health.


Assuntos
Saúde , Neoplasias Cutâneas , Luz Solar , Raios Ultravioleta , Vitamina D , Humanos , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/prevenção & controle , Medição de Risco , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/prevenção & controle , Deficiência de Vitamina D/epidemiologia
12.
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
13.
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
14.
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
15.
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
16.
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
17.
Adv Exp Med Biol ; 1268: 319-331, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918226

RESUMO

Sunlight, in particular UV-B radiation, is an important factor for endogenous vitamin D production as 80-90% of the required vitamin D needs to be photosynthesized in the skin. The active form of vitamin D, vitamin D3 or calcitriol, binds to the ligand-activated transcription factor vitamin D receptor (VDR) for genomic and non-genomic effects. Recently, calcitriol and analogs have been shown to have antiproliferative effects in mouse and human BCC and SCC cell lines in vitro. As UV radiation plays a critical role in the photosynthesis of vitamin D, stringent sun protection, as recommended for xeroderma pigmentosum (XP) patients, may impact their vitamin D levels.XP is a rare autosomal recessive disorder with a worldwide prevalence of 1 in 1,000,000. XP can be divided into seven different complementation groups: XP-A to XP-G. The complementation groups correspond with the underlying gene defect. Defects in these genes lead to a defective nucleotide excision repair (NER), which is necessary to remove UV-induced DNA damage such as the UV photoproducts cyclobutane pyrimidine dimers (CPD) and 6-4 pyrimidine-pyrimidone (6-4 PP) dimer. Additionally, a variant form with a mutation in the translational polymerase η gene (PolH), also called XP variant (XPV), exists. Patients with XPV show a defect in translesion synthesis. Due to their inability to repair UV-induced lesions, XP patients exhibit an increased risk for UV-induced nonmelanoma skin cancer (NMSC) such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) as well as melanoma. Although no curative therapy for XP exists today, numerous options for the treatment and prophylaxis of skin cancer have become available.


Assuntos
Luz Solar , Vitamina D , Xeroderma Pigmentoso , Animais , Humanos , Raios Ultravioleta , Vitamina D/biossíntese , Vitaminas/biossíntese , Xeroderma Pigmentoso/genética , Xeroderma Pigmentoso/metabolismo
18.
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
19.
Adv Exp Med Biol ; 1268: 335-353, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918227

RESUMO

Although great progress has been achieved during the last decades, the clinical management of organ transplant recipients (OTRs) remains a challenge. OTRs need in general lifelong immunosuppressive therapy that is associated with an increased risk to develop skin cancer and with an unfavorable clinical outcome of these malignancies. Skin cancer prevention measures, including regular full-body examinations, are therefore necessary in OTRs to detect and treat suspicious lesions at an early stage. The frequency of aftercare depends on the individual risk factors of the patient. Patients should apply consistent sun protection with sunscreens and clothing, as well as a monthly self-examination. On the other hand, the need of UVR avoidance increases the risk of vitamin D deficiency, which itself is associated with an increased risk for many diseases, including malignancies. OTRs should therefore be monitored for 25(OH)D status and/or should take vitamin D supplements. It has to be emphasized that an interdisciplinary approach, coordinated by the transplant center, that includes regular skin examinations by a dermatologist, is needed to ensure the best care for the OTRs.


Assuntos
Neoplasias Cutâneas/diagnóstico , Transplantados , Raios Ultravioleta , Vitamina D , Humanos , Imunossupressão/efeitos adversos , Neoplasias Induzidas por Radiação/diagnóstico , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Cutâneas/epidemiologia , Transplantados/estatística & dados numéricos , Vitamina D/administração & dosagem , Vitamina D/sangue , Vitaminas/administração & dosagem , Vitaminas/sangue
20.
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
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