Inflammation is a defence response to tissue damage that requires tight regulation in order to prevent impaired healing. Tissue-resident macrophages have a key role in tissue repair
, but the precise ...molecular mechanisms that regulate the balance between inflammatory and pro-repair macrophage responses during healing remain poorly understood. Here we demonstrate a major role for sensory neurons in promoting the tissue-repair function of macrophages. In a sunburn-like model of skin damage in mice, the conditional ablation of sensory neurons expressing the Gα
-interacting protein (GINIP) results in defective tissue regeneration and in dermal fibrosis. Elucidation of the underlying molecular mechanisms revealed a crucial role for the neuropeptide TAFA4, which is produced in the skin by C-low threshold mechanoreceptors-a subset of GINIP
neurons. TAFA4 modulates the inflammatory profile of macrophages directly in vitro. In vivo studies in Tafa4-deficient mice revealed that TAFA4 promotes the production of IL-10 by dermal macrophages after UV-induced skin damage. This TAFA4-IL-10 axis also ensures the survival and maintenance of IL-10
TIM4
dermal macrophages, reducing skin inflammation and promoting tissue regeneration. These results reveal a neuroimmune regulatory pathway driven by the neuropeptide TAFA4 that promotes the anti-inflammatory functions of macrophages and prevents fibrosis after tissue damage, and could lead to new therapeutic perspectives for inflammatory diseases.
Skin color diversity is the most variable and noticeable phenotypic trait in humans resulting from constitutive pigmentation variability. This paper will review the characterization of skin ...pigmentation diversity with a focus on the most recent data on the genetic basis of skin pigmentation, and the various methodologies for skin color assessment. Then, melanocyte activity and amount, type and distribution of melanins, which are the main drivers for skin pigmentation, are described. Paracrine regulators of melanocyte microenvironment are also discussed. Skin response to sun exposure is also highly dependent on color diversity. Thus, sensitivity to solar wavelengths is examined in terms of acute effects such as sunburn/erythema or induced-pigmentation but also long-term consequences such as skin cancers, photoageing and pigmentary disorders. More pronounced sun-sensitivity in lighter or darker skin types depending on the detrimental effects and involved wavelengths is reviewed.
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•The safety issues of artificial sunscreen are controversial by their photostability, toxicity and destructive marine ecosystems.•Natural selection and evolution have ensured plants ...have developed effective protection mechanisms against ROS and UV.•Natural components in sunscreens are increasingly common.
Artificial sunscreens are already gaining traction in order to protect the skin from sunburns, photoaging and photocarcinogenesis. However, the efficacy and safety of most artificial sunscreen constituents are hindered by their photostability, toxicity and damage to marine ecosystems. Natural selection and evolution have ensured that plants and animals have developed effective protective mechanisms against the deleterious side effects of oxidative stress and ultraviolet radiation (UV). Hence, natural antioxidants such as sun blockers are drawing considerable attention. The exact mechanism by which natural components act as sunscreen molecules has not been clearly established. However, conjugated π system is reported to play an important role in protecting the vital genetic material within the organism. Compared to artificial sunscreens, natural sunscreens with strong UV absorptive capacities are largely limited by low specific extinction value and by their inability to spread in large-scale sunscreen cosmetic applications. Previous studies have documented that natural components exert their photoprotective effects (such as improved skin elasticity and hydration, skin texture, and wrinkles) through their antioxidant effects, and through the regulation of UV-induced skin inflammation, barrier impairment and aging. This review focuses on natural antioxidant topical formulations with sun protection factor (SPF). Lignin, melanin, silymarin and other ingredients have been added to high sun protection nature sunscreens without any physical or chemical UV filters. This paper also provides a reference for adopting novel technical measures (extracting high content components, changing the type of solution, optimizing formulation, applying Nano technology, et al) to design and prepare nature sunscreen formulations equated with commercial sunscreen formulations. Another strategy is to add natural antioxidants from plants, animals, microorganisms and marine organisms as special enhancer or modifier ingredients to reinforce SPF values. Although the photoprotective effects of natural components have been established, their deleterious side effects have not been elucidated.
Despite numerous observational studies indicating an increased risk of cutaneous melanoma (CM) due to childhood sunburn, no studies have established a definitive cause‐and‐effect relationship. ...Therefore, our objective was to employ a Mendelian randomization (MR) design to explore a possible causal association between childhood sunburn and the risk of CM. To investigate the causal relationship between childhood sunburn and CM, we used large‐scale genetic summary‐level data from genome‐wide association studies (GWAS), including childhood sunburn (n = 346,955) and CM (n = 262,288), building upon previous observational studies. In the analysis, we mainly used the inverse‐variance weighted (IVW) method of the random effects model, supplemented by the weighted median method and MR‐Egger method. The results of the IVW method demonstrated that genetically predicted childhood sunburn was significantly associated with higher odds of CM, with an odds ratio (OR) of 2.418 (95%CI, 1.426–4.099; p = .001). The weighted median method and MR‐Egger regression also demonstrated directionally similar results (both p < .05). Furthermore, both the funnel plot and the MR‐Egger intercepts showed the absence of directional pleiotropy between childhood sunburn and CM. Our study offers potential evidence linking genetically predicted childhood sunburn with CM, underscoring the need for individuals with a history of childhood sunburn to be extra vigilant regarding the occurrence of CM.
This article explores the potential causal relationship between childhood sunburn and the risk of melanoma through a Mendelian randomization design. The results suggest a positive correlation between genetically predicted childhood sunburn and the risk of melanoma. Therefore, this study provides potential evidence linking childhood sunburn to melanoma and suggests that individuals with a history of childhood sunburn should be more vigilant in preventing melanoma.
Public education mass media campaigns are an important intervention for influencing behaviour modifications. However, evidence on the effectiveness of such campaigns to encourage the population to ...reduce sun exposure is limited. This study investigates the benefits and costs of three skin cancer campaigns implemented in New South Wales from 2006-2013. This analysis uses Australian dollars (AUD) and 2010-11 as the currency and base year, respectively. Historical data on skin cancer were used to project skin cancer rates for the period 2006-2020. The expected number of skin cancer cases is derived by combining skin cancer rates, sunburn rates and relative risk of skin cancers due to sun exposure. Counterfactual estimates are based on sunburn exposure in the absence of the campaigns. Monetary values are attached to direct (treatment) and indirect (productivity) costs saved due to fewer skin cancer cases. Monetary benefits are compared with the cost of implementing the campaigns and are presented in the form of a benefit-cost ratio. Relative to the counterfactual (i.e., no campaigns) there are an estimated 13,174 fewer skin cancers and 112 averted deaths over the period 2006-2013. The net present value of these benefits is $60.17 million and the campaign cost is $15.63 million. The benefit cost ratio is 3.85, suggesting that for every $1 invested a return of $3.85 is achieved. Skin cancer public education mass media campaigns are a good investment given the likely extent to which they reduce the morbidity, mortality and economic burden of skin cancer.
Sunscreens containing titanium dioxide (TiO(2)) and zinc oxide (ZnO) nanoparticles (NP) are effective barriers against ultraviolet B (UVB) damage to skin, although little is known about their ...disposition in UVB-damaged skin. Pigs were exposed to UVB that resulted in moderate sunburn. For in vitro studies, skin in flow-through diffusion cells were treated 24 h with four sunscreen formulations as follows: 10% coated TiO(2) in oil/water (o/w), 10% coated TiO(2) in water/oil (w/o), 5% coated ZnO in o/w, and 5% uncoated ZnO in o/w. TiO(2) (rutile, crystallite) primary particle size was 10 × 50 nm with mean agglomerates of 200 nm (range ca. 90 nm--460 nm); mean for ZnO was 140 nm (range ca. 60--200 nm). Skin was processed for light microscopy, scanning (SEM) and transmission electron microscopy (TEM), and time-of-flight secondary ion mass spectrometry (TOF-SIMS). UVB-exposed skin had typical sunburn histology. TEM showed TiO(2) NP 17 layers into stratum corneum (SC), whereas ZnO remained on the surface. TOF-SIMS showed TiO(2) and ZnO epidermal penetration in both treatments. Perfusate analyzed by TEM/energy dispersive x-ray spectroscopy or inductively coupled plasma mass spectrometry detected no Ti or Zn, indicating minimal transdermal absorption. In vivo, skin was dosed at 24 h occluded with formulations and at 48 h. TiO(2) NP in o/w formulation penetrated 13 layers into UVB-damaged SC, whereas only 7 layers in normal skin; TiO(2) in w/o penetrated deeper in UVB-damaged SC. Coated and uncoated Zn NP in o/w were localized to the upper one to two SC layers in all skin. By SEM, NP were localized as agglomerates in formulation on the skin surface and base of hair. TOF-SIMS showed Ti within epidermis and superficial dermis, whereas Zn was limited to SC and upper epidermis in both treatments. In summary, UVB-damaged skin slightly enhanced TiO(2) NP or ZnO NP penetration in sunscreen formulations but no transdermal absorption was detected.
Cutaneous inflammation from UV radiation exposure causes epidermal damage, cellular infiltration, and secretion of pro-inflammatory mediators that exacerbate tissue destruction. Recovery is mediated ...chiefly by anti-inflammatory M2 macrophages that suppress inflammation and augment epidermal regeneration. Vitamin D enables anti-inflammation to promote tissue repair in response to injury. Since vitamin D enhances cellular macroautophagy/autophagy, we investigated the role of autophagy in vitamin D protection of UV-mediated sunburn and inflammation. Using a UV-mediated acute skin injury mouse model, we demonstrate that a single dose of vitamin D resolves injury with sustained inhibition of inflammatory cytokines associated with enhanced autophagy in myeloid anti-inflammatory M2 macs. Increased MAP1LC3B/LC3 expression corroborated with complete autolysosome formation detected by electron microscopy and correlated with degradation of SQSTM1/p62 in the skin following vitamin D treatment. Specifically, pharmacological inhibition of autophagy increased UV-induced apoptosis, suppressed M2 macs recruitment, and prevented vitamin D downregulation of Tnf and Mmp9 in the skin. Furthermore, selective deletion of autophagy in myeloid cells of atg7 cKO mice abrogated vitamin D-mediated protection and recapitulated UV-induced inflammation. Mechanistically, vitamin D signaling activated M2-autophagy regulators Klf4, Pparg, and Arg1. Lastly, analysis of UV-exposed human skin biopsies detected a similar increase in macrophage autophagy following vitamin D intervention, identifying an essential role for autophagy in vitamin D-mediated protection of skin from UV damage.
Abbreviations: ARG1: arginase 1; ATG7 cKO: autophagy related 7 conditional knockout; HPF: high powered field; KLF4: Kruppel like factor 4; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; macs: macrophage; 3-MA: 3-methyladenine; MMP9: matrix metallopeptidase 9; NOS2: nitric oxide synthase 2, inducible; PPARG: peroxisome proliferator activated receptor gamma; SQSTM1/p62: sequestosome 1; TNF: tumor necrosis factor; UV: ultraviolet; VD: vitamin D, 25-hydroxy vitamin D
3
; 1,25-VD: 1, 25-dihydroxy vitamin D
3
Background Exposure to ultraviolet radiation (from solar and nonsolar sources) is a risk factor for skin cancer. Objective We sought to summarize recent estimates on sunburns, sun-protection ...behaviors, and indoor tanning available from national and selected statewide behavioral surveys. Methods Estimates of the prevalence of sunburn, sun-protection behaviors, and indoor tanning by US adults, adolescents, and children collected in national surveys in 1992, 2004 to 2005, and 2007 to 2009 were identified and extracted from searches of computerized databases (ie, MEDLINE and PsychINFO), reference lists, and survey World Wide Web sites. Sunburn estimates from 3 state Behavioral Risk Factors Surveillance Systems were also analyzed. Results Latest published estimates (2005) showed that 34.4% of US adults were sunburned in the past year. Incidence of sunburns was highest among men, non-Hispanic whites, young adults, and high-income groups in national surveys. About 3 in 10 adults routinely practiced sun-protection behaviors, and women and older adults took the most precautions. Among adolescents, 69% were sunburned in the previous summer and less than 40% practiced sun protection. Approximately 60% of parents applied sunscreen and a quarter used shade to protect children. Indoor tanning was prevalent among younger adults and females. Limitations Limitations include potential recall errors and social desirability in self-report measures, and lack of current data on children. Conclusion Many Americans experienced sunburns and a minority engaged in protective behaviors. Females and older adults were most vigilant about sun protection. Substantial proportions of young women and adolescents recently used indoor tanning. Future efforts should promote protective hats, clothing, and shade; motivate males and younger populations to take precautions; and convince women and adolescents to reduce indoor tanning.
The objective of this study was to analyse the sun exposure habits of elite aquatics athletes, together with their sunburn history and skin examination habits, taking into account differences by sex ...and between sports. A cross-sectional health survey was conducted at world championship events during which elite surfers, windsurfers and Olympic sailors from 30 different countries were invited to participate. The athletes were asked to complete a self-administered questionnaire focused on sun protection habits, sun exposure and sports practices. The survey was completed by 240 athletes, 171 men (71.3%) and 69 women (28.8%), with a mean age of 22 years (SD 5.86) and skin phototypes I (6.3%), II (3.3%), III (22.0%), IV (32.5%), V (9.2%) and VI (1.7%). There were significant differences between male and female athletes in skin self-examination (
p
< 0.001) and in the use of sunglasses (
p
< 0.001). In sunburn history during the last season, there were significant differences (
p
< 0.001) among the three sports analysed, in both sexes. The mean rate of sunburn during the previous season was 76.7%, and 27.5% of participants reported having experienced three or more sunburns that lasted at least 1 day. This type of athlete is at high risk of sunburn and hence of future skin cancer. However, there is a general lack of awareness of this risk. This study highlights the need to inform such athletes and to raise awareness of the dangers, through educational interventions on the importance of protecting against sunburn in order to reduce the future incidence of skin cancer.
Individuals can reduce the risk of developing skin cancer by minimizing ultraviolet sunlight exposure, though recent trends in sun-protective behaviors remain to be investigated. To ...evaluate sun-protective behaviors and sunburn among US adults. We analyzed data from the 2010, 2015, and 2020 National Health Interview Survey (NHIS), an annual, cross-sectional survey conducted by the US Census Bureau. Multivariable regression models were stratified by demographic variables and constructed to evaluate sun-protective behaviors and sunburn avoidance across time. From 2010 through 2020, US adults had significantly increased prevalence of seeking shade (
p
value, 0.003), wearing wide-brimmed hats (< 0.001), wearing long-sleeved shirts (< 0.001), using sunscreen (< 0.001), and avoiding sunburns (< 0.001) and significantly decreased prevalence of sun avoidance (< 0.001). Disparities in sun-protective behaviors also exist among different sexes, ages, education levels, and those reporting higher sun sensitivity. This cross-sectional study found that by 2020, US adults had an increased prevalence of wearing sun-protective clothing and sunscreen use, though decreased prevalence of sun avoidance. Although certain sun-protective behaviors have become more prevalent, the incidence of skin cancer continues to rise. Efforts to understand drivers of sun-protective behaviors and targeted intervention efforts are needed.
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