RESUMO
Ultraviolet B (UVB) radiation induces cutaneous inflammation, leading to thermal and mechanical hypersensitivity. Here, we examine the mechanical properties and profile of tactile and nociceptive peripheral afferents functionally disrupted by this injury and the role of oxytocin (OXT) as a modulator of this disruption. We recorded intracellularly from L4 afferents innervating the irradiated area (5.1 J/cm2) in 4-6 old week male mice (C57BL/6J) after administering OXT intraperitoneally, 6 mg/Kg. The distribution of recorded neurons was shifted by UVB radiation to a pattern observed after acute and chronic injuries and reduced mechanical thresholds of A and C- high threshold mechanoreceptors while reducing tactile sensitivity. UVB radiation did not change somatic membrane electrical properties or fiber conduction velocity. OXT systemic administration rapidly reversed these peripheral changes toward normal in both low and high-threshold mechanoreceptors and shifted recorded neuron distribution toward normal. OXT and V1aR receptors were present on the terminals of myelinated and unmyelinated afferents innervating the skin. We conclude that UVB radiation, similar to local tissue surgical injury, cancer metastasis, and peripheral nerve injury, alters the distribution of low and high threshold mechanoreceptors afferents and sensitizes nociceptors while desensitizing tactile units. Acute systemic OXT administration partially returns all of those effects to normal.
Assuntos
Nociceptividade , Ocitocina , Camundongos , Masculino , Animais , Ocitocina/farmacologia , Ocitocina/uso terapêutico , Camundongos Endogâmicos C57BL , Tato/fisiologia , Pele/inervação , Mecanorreceptores , Nociceptores/fisiologiaRESUMO
BACKGROUND: Long-term exposure to UVB induces DNA damage, inflammatory response, mitochondrial dysfunction, and apoptosis in skin cells, thus causing skin photodamage. Research has demonstrated the noteworthy antioxidant, anti-inflammatory, DNA repair, and mitochondrial protective properties of keratinocyte growth factor-2 (KGF-2). METHODS: To examine the impact of KGF-2 on UVB-triggered skin photodamage in mice, hair-removed mice were initially exposed under UVB radiation and subsequently treated with KGF-2 hydrogel and repeated for 6 days. On day 7, the assessment of histopathological alterations, inflammation, DNA damage, mitochondrial function, and apoptosis in mouse skin was assessed. RESULTS: It was found that KGF-2 could effectively relieve cutaneous photodamage symptoms and inhibit epidermal proliferation in mice. Meanwhile, KGF-2 was found to significantly reduce DNA damage, attenuate the inflammatory response, and inhibit the mitochondria-mediated intrinsic apoptotic pathway in the UVB-exposed mouse skin photodamage model. CONCLUSION: To summarize, our results indicated that KGF-2 reduces the severity of mouse skin photodamage caused by UVB rays by attenuating DNA damage and the inflammatory response, besides inhibiting the mitochondria-mediated intrinsic apoptosis pathway.
Assuntos
Apoptose , Dano ao DNA , Fator 7 de Crescimento de Fibroblastos , Mitocôndrias , Pele , Raios Ultravioleta , Animais , Feminino , Camundongos , Apoptose/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Fator 7 de Crescimento de Fibroblastos/farmacologia , Inflamação/patologia , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Pele/patologia , Pele/metabolismo , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversosRESUMO
To evaluate the efficacy of yellow light-emitting diode (LED) irradiation at 590 nm, alone or in combination with anti-inflammatory active substances against ultraviolet (UV)-induced inflammation in keratinocytes. HaCaT keratinocytes were pretreated with LED yellow light (590 nm) alone or in combination with an antiinflammatory active substance such as glycerophosphoinositol choline (GC), extract of grains of paradise (Aframomum melegueta Schum, AM), or a bisabolol and ginger root extract mixture (Bb-GE) before UVB irradiation. Following each treatment, we measured the levels of inflammatory mediators secreted by keratinocytes. HaCaT keratinocytes treated with UVB (300 mJ cm-²) and then cultured for 24 h exhibited significantly upregulated expression of proinflammatory factors, including interleukin (IL)-1α, prostaglandin E2 (PGE2), and IL-8. After pretreatment with 590 nm LED, UVB-induced inflammatory responses were significantly inhibited. Co-pretreatment with 590 nm LED irradiation and GC further inhibited the expression of IL-1α and IL-8. IL-8 expression was inhibited by co-pretreatment with 590 nm LED irradiation and AM, whereas PGE2 expression was inhibited by co-pretreatment with 590 nm LED irradiation and Bb-GE. Co-treatment with 590 nm LED irradiation and various active substances modulated UVB-induced inflammation in keratinocytes, suggesting the potential application of this approach to prevent damage caused by voluntary sun exposure in daily life.
Assuntos
Inflamação , Interleucina-8 , Queratinócitos , Raios Ultravioleta , Humanos , Queratinócitos/efeitos da radiação , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Raios Ultravioleta/efeitos adversos , Interleucina-8/metabolismo , Dinoprostona/metabolismo , Interleucina-1alfa/metabolismo , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Lasers Semicondutores/uso terapêutico , Anti-Inflamatórios/farmacologia , Sesquiterpenos Monocíclicos/farmacologia , Células HaCaTRESUMO
The current study examined the impact of ultraviolet (UV)-B radiation in Metarhizium pingshaense blastospores' photolyase expression and their virulence against Rhipicephalus microplus. Blastospores were exposed to UV under laboratory and field conditions. Ticks were treated topically with fungal suspension and exposed to UV-B in the laboratory for three consecutive days. The expression of cyclobutane pyrimidine dimmers (CPDs)-photolyase gene maphr1-2 in blastospores after UV exposure followed by white light exposure was accessed after 0, 8, 12, 24, 36, and 48 h. Average relative germination of blastospores 24 h after in vitro UV exposure was 8.4% lower than 48 h. Despite this, the relative germination of blastospores exposed to UV in the field 18 h (95.7 ± 0.3%) and 28 h (97.3 ± 0.8%) after exposure were not different (p > 0.05). Ticks treated with fungus and not exposed to UV exhibited 0% survival 10 days after the treatment, while fungus-treated ticks exposed to UV exhibited 50 ± 11.2% survival. Expression levels of maphr1-2 8, 12, and 24 h after UV-B exposure were not different from time zero. Maphr1-2 expression peak in M. pingshaense blastospores occurred 36 h after UV-B exposure, in the proposed conditions and times analyzed, suggesting repair mechanisms other than CPD-mediated-photoreactivation might be leading blastospores' germination from 0 to 24 h.
Assuntos
Desoxirribodipirimidina Fotoliase , Metarhizium , Rhipicephalus , Animais , Rhipicephalus/metabolismo , Rhipicephalus/microbiologia , Desoxirribodipirimidina Fotoliase/genética , Desoxirribodipirimidina Fotoliase/metabolismo , Virulência , Luz , Raios Ultravioleta , Metarhizium/metabolismo , Controle Biológico de VetoresRESUMO
The Antarctic environment is extremely cold, windy and dry. Ozone depletion has resulted in increasing ultraviolet-B radiation, and increasing greenhouse gases and decreasing stratospheric ozone have altered Antarctica's climate. How do mosses thrive photosynthetically in this harsh environment? Antarctic mosses take advantage of microclimates where the combination of protection from wind, sufficient melt water, nutrients from seabirds and optimal sunlight provides both photosynthetic energy and sufficient warmth for efficient metabolism. The amount of sunlight presents a challenge: more light creates warmer canopies which are optimal for photosynthetic enzymes but can contain excess light energy that could damage the photochemical apparatus. Antarctic mosses thus exhibit strong photoprotective potential in the form of xanthophyll cycle pigments. Conversion to zeaxanthin is high when conditions are most extreme, especially when water content is low. Antarctic mosses also produce UV screening compounds which are maintained in cell walls in some species and appear to protect from DNA damage under elevated UV-B radiation. These plants thus survive in one of the harshest places on Earth by taking advantage of the best real estate to optimise their metabolism. But survival is precarious and it remains to be seen if these strategies will still work as the Antarctic climate changes.
Assuntos
Briófitas , Luz Solar , Regiões Antárticas , Raios Ultravioleta , ÁguaRESUMO
Papuloerythroderma of Ofuji (PEO) is an uncommon disease characterised by widespread erythroderma composed of intensely pruritic solid papules coalescing into plaques sparing the skin folds (deck-chair sign). The pathogenesis of PEO remains unclear, although T helper (Th) 2 and Th22 cells may play an important role. Dupilumab is an interleukin (IL)-4 receptor α-antagonist that effectively reduces Th2 responses, which has drawn increasing attention in the treatment of PEO patients. Here, we reported a successful case of dupilumab treatment in combination with ultraviolet B (UVB) radiation therapy, which is well known and effective for chronic itch. The patient had a significant decrease in visual analogue scale (VAS) score and eosinophil after only 1 week of treatment, which may be due to the combination effect.
Assuntos
Dermatite Esfoliativa , Dermatopatias Papuloescamosas , Terapia Ultravioleta , Humanos , Dermatopatias Papuloescamosas/patologia , Dermatite Esfoliativa/patologiaRESUMO
The ultraviolet-B (UV-B) radiation is harmful to the aquatic organisms. The UV-B protective properties of leaves and seeds of herb Achyranthes aspera were evaluated in Clarias batrachus. Fish were fed with four diets-EFL1, EFL2 containing 0.25 and 0.5% leaves, EFS containing 0.5% seeds and control, CF. After 83 days of feeding, fish were exposed to UV-B (157 µW/cm2) for 7 days at the rate of 15 min/day. One batch of fish in each treatment was kept unexposed. Significantly higher final weight was found in EFS followed by EFL2 and EFL1 treatments. It was higher in unexposed fish compared to the exposed ones. Among exposed fish, significantly higher lysozyme was found in EFS and myeloperoxidase in EFS and EFL2 compared to others. Nitric oxide synthase and superoxide dismutase levels were significantly higher in liver and head kidney of EFS diet fed fish compared to others. Thiobarbituric acid reactive substances (TBARS) and carbonyl protein levels were minimum in EFS followed by EFL2. The independent sample t-test showed that nitric oxide synthase was significantly higher and myeloperoxidase and TBARS levels were significantly lower in unexposed group compared to the exposed fish in respective treatment. There were up-regulations of TNF-α, iNOS, NF-kB, BAX, Cytochrome c, SOD-c, Caspase 3, Caspase 9, BCL2 in liver and head kidney of leaves and seeds incorporated diets fed fish compared to control. Supplementation of A. aspera seeds and leaves at 0.5% level in diets gave UV-B protection to the fish.
Assuntos
Achyranthes , Peixes-Gato , Achyranthes/química , Animais , Peroxidase/análise , Folhas de Planta , Sementes/química , Substâncias Reativas com Ácido Tiobarbitúrico/análiseRESUMO
OBJECTIVES: Solar ultraviolet B radiation (UV) may reduce the risk of cancer, including colorectal cancer (CRC), although the evidence is inconclusive. To contribute with evidence, the present largescale register-based nested case-control study aimed to investigate the association between occupational UV exposure and CRC in Denmark. METHODS: The Danish Cancer Registry was used to identify a total of 12,268 men and women diagnosed with primary CRC before age 70. Five controls matched on year of birth and sex, alive and free of CRC at the time of diagnosis of the index case were randomly selected from The Danish Civil Registration System. Occupational UV exposure was assessed by obtainment of full employment history from the Danish Supplementary Pension Fund Register, which was linked to a job exposure matrix. Conditional logistic regression was used to estimate odds ratios (ORs) with corresponding 95% confidence intervals. RESULTS: We observed an inverse association between longer duration of UV exposure and CRC in women (≥20 years: OR = 0.84, 95% CI: 0.69-1.03), while no noteworthy associations were observed in men. When focusing on colon cancer only, longer duration of UV exposure (>20 years: OR = 0.92, 95% CI: 0.83-1.01) and higher cumulative UV exposure (highest exposure category: OR = 0.90, 95% CI: 0.83-0.99) were indicated to lower the risk in the study population including both men and women, although the risk reduction appeared to be more evident for women. No consistent risk patterns were observed for rectal cancer. CONCLUSIONS: The present study suggests a modest protective effect from long-term occupational UV exposure on the risk of colon cancer. The effect may be greater in women and these findings need further attention in future large-scale studies.
Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Exposição Ocupacional , Adulto , Idoso , Estudos de Casos e Controles , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Raios Ultravioleta/efeitos adversos , Adulto JovemRESUMO
The Yellow Sea green tide (YSGT) is the world's largest transregional macroalgal blooms, and the causative species Ulva prolifera (U. prolifera) suffers from ultraviolet-b radiation (UVBR) during the floating migration process. Previous study confirmed that U. prolifera displayed a wide variety of physiological responses characterized as acclimation to UVBR, while the response mechanisms against low-dose and short-term radiation (LDSTR) are not clear. A study with photosynthetically active radiation (PAR) and UVBR was designed: normal light (NL: 72 µmol photons m-2 s-1), NL+0.3 (UVBR: 0.3 W·m-2), and NL+1.6 (UVBR: 1.6 W·m-2). The results showed that high-dose UVBR inhibited photosynthesis in thalli, especially under long-term exposure, while a variety of physiological responses were observed under LDSTR. The inhibition of photosynthesis appeared to be ameliorated by the algae under LDSTR. Further analysis showed that U. prolifera achieved balancing damage by means of non-photochemical quenching (NPQ), accumulation of phenolic compounds coupled with the ASA-GSH cycle involved in the antioxidant process and enhanced photorespiratory metabolism under LDSTR. This study provides new insights into the balancing damage mechanisms of U. prolifera under LDSTR, enabling the thalli to adapt to the light conditions during the long duration and distance involved in floating migration.
Assuntos
Ulva , Adaptação Fisiológica , Fotossíntese , Raios Ultravioleta/efeitos adversos , Ulva/metabolismoRESUMO
OBJECTIVE: The aim of this study was to provide a non-invasive imaging method to evaluate the physical and mechanical parameters as a novelty method during skin photoaging. METHODS: In order to evaluate the process of skin damage, 25 mice (C57BL6) were exposed to UVB radiation (0.03 mW/cm2 ), 5 times a week for 5 weeks. The thickness of the epidermal and dermal layers was measured weekly from the ultrasound images (40 MHz). The elastic parameters of the skin were estimated from the processing of the sequential ultrasound images with the motion detection algorithm during the injury generation process. RESULTS: The thickening, Young modulus, and shear modulus of the dermal and epidermal layers during the UVB damage process significantly increased during the 5-week study period (P < .05). In addition, the percentage of changes in the thickness of the epidermal layer (0.22 ± 0.01 mm in day 0 to 0.37 ± 0.02 mm in day 35) and dermal layer (0.57 ± 0.05 mm in day 0 to 0.90 ± 0.08 mm in day 35) increased by 68% and 57%, respectively. Furthermore, Young modulus (154.41 ± 8.8 kPa) was 11 times more than that of non-irradiated skin (14.90 ± 2.2 kPa) and the shear modulus (2.33 ± 0.04 kPa) was 2.2 times more than non-irradiated skin (1.06 ± 0.04 kPa). CONCLUSION: With processing the sequential ultrasound images and extracting the thickening, the elasticity of the skin layers can detect skin lesions by UVB radiation.
Assuntos
Pele/diagnóstico por imagem , Pele/efeitos da radiação , Ultrassonografia/métodos , Raios Ultravioleta , Algoritmos , Animais , Módulo de Elasticidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos AnimaisRESUMO
Gradients in cuticle lightness of ectotherms have been demonstrated across latitudes and elevations. Three key hypotheses have been used to explain these macroecological patterns: the thermal melanism hypothesis (TMH), the melanism-desiccation hypothesis (MDH) and the photo-protection hypothesis (PPH). Yet the broad abiotic measures, such as temperature, humidity and UV-B radiation, typically used to detect these ecogeographical patterns, are a poor indication of the microenvironment experienced by small, cursorial ectotherms like ants. We tested whether these macroecological hypotheses explaining cuticle lightness held at habitat and microclimatic level by using a vertical gradient within a tropical rainforest. We sampled 222 ant species in lowland, tropical rainforest across four vertical strata: subterranean, ground, understory and canopy. We recorded cuticle lightness, abundance and estimated body size for each species and calculated an assemblage-weighted mean for cuticle lightness and body size for each vertical stratum. Abiotic variables (air temperature, vapour pressure deficit and UV-B radiation) were recorded for each vertical stratum. We found that cuticle lightness of ant assemblages was vertically stratified: ant assemblages in the canopy and understory were twice as dark as assemblages in ground and subterranean strata. Cuticle lightness was not correlated with body size, and there was no support for the TMH. Rather, we attribute this cline in cuticle lightness to a combination of the MDH and the PPH. Our findings indicate that broad macroecological patterns can be detected at much smaller spatial scales and that microclimatic gradients can shape trait variation, specifically the cuticle lightness of ants. These results suggest that any changes to microclimate that occur due to land-use change or climate warming could drive selection of ants based on cuticle colour, altering assemblage structure and potentially ecosystem functioning.
Assuntos
Formigas , Microclima , Animais , Cor , Ecossistema , Floresta ÚmidaRESUMO
Ozone layer depletion leads to elevated ultraviolet-B (UV-B) radiation, which affects plant growth; however, little is known about the relationship between root growth and signaling molecules in roots. Therefore, in this work, simulated UV-B radiation was used to study the effects of elevated UV-B radiation on root growth of soybean seedlings and changes in the content of signaling molecules in roots. The results showed that compared with the control, the 2.63â¯kJâ¯m-2 d-1 and 6.17â¯kJâ¯m-2 d-1 elevated UV-B radiation treatments inhibited root growth, and root growth parameters (total root length, root surface area, root volume, average diameter, root tip number, and root dry weight) all decreased. For root signaling molecules, the content of nitric oxide, reactive oxygen species, abscisic acid, salicylic acid, and jasmonic acid increased, and the content of auxin, cytokinin, and gibberellin decreased. The above indices changed more significantly under the 6.17â¯kJâ¯m-2 d-1 treatment. After withdrawal of the exposure, the above indices could be restored to a certain extent. These data indicated that UV-B radiation interfered with root growth by affecting the content of signaling molecules in roots, and the degree of the effects was related to the intensity of UV-B radiation. The results from this study provide a theoretical basis for studying the preliminary mechanism of elevated UV-B radiation on root growth and possible pathways that can mitigate UV-B radiation damage for root growth. ONE SENTENCE SUMMARY: The effects of elevated UV-B on root growth of soybean seedlings were regulated by signaling molecules, and the degree of the effects was related to the intensity of UV-B radiation.
Assuntos
Glycine max/efeitos da radiação , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/efeitos da radiação , Transdução de Sinais/efeitos da radiação , Raios Ultravioleta , Ácido Abscísico/metabolismo , Ciclopentanos/metabolismo , Citocininas/metabolismo , Relação Dose-Resposta à Radiação , Giberelinas/metabolismo , Ácidos Indolacéticos/metabolismo , Óxido Nítrico/metabolismo , Oxilipinas/metabolismo , Desenvolvimento Vegetal/efeitos da radiação , Reguladores de Crescimento de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ácido Salicílico/metabolismo , Plântula/efeitos dos fármacos , Plântula/metabolismo , Glycine max/metabolismoRESUMO
Horse oil products have been used in skin care for a long time in traditional medicine, but the biological effects of horse oil on the skin remain unclear. This study was conducted to evaluate the protective effect of horse oil on ultraviolet B (UVB)-induced oxidative stress in human HaCaT keratinocytes. Horse oil significantly reduced UVB-induced intracellular reactive oxygen species and intracellular oxidative damage to lipids, proteins, and DNA. Horse oil absorbed light in the UVB range of the electromagnetic spectrum and suppressed the generation of cyclobutane pyrimidine dimers, a photoproduct of UVB irradiation. Western blotting showed that horse oil increased the UVB-induced Bcl-2/Bax ratio, inhibited mitochondria-mediated apoptosis and matrix metalloproteinase expression, and altered mitogen-activated protein kinase signaling-related proteins. These effects were conferred by increased phosphorylation of extracellular signal-regulated kinase 1/2 and decreased phosphorylation of p38 and c-Jun N-terminal kinase 1/2. Additionally, horse oil reduced UVB-induced binding of activator protein 1 to the matrix metalloproteinase-1 promoter site. These results indicate that horse oil protects human HaCaT keratinocytes from UVB-induced oxidative stress by absorbing UVB radiation and removing reactive oxygen species, thereby protecting cells from structural damage and preventing cell death and aging. In conclusion, horse oil is a potential skin protectant against skin damage involving oxidative stress.
Assuntos
Queratinócitos/patologia , Queratinócitos/efeitos da radiação , Óleos/farmacologia , Estresse Oxidativo/efeitos da radiação , Raios Ultravioleta , Absorção de Radiação , Animais , Apoptose/efeitos da radiação , Linhagem Celular , Ativação Enzimática/efeitos da radiação , Cavalos , Humanos , Queratinócitos/enzimologia , Sistema de Sinalização das MAP Quinases/efeitos da radiação , Metaloproteinases da Matriz/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Nostoc flagelliforme is a pioneer organism in the desert and highly resistant to ultraviolet B (UV-B) radiation, while the involved adaptive mechanism has not been fully explored yet. To elucidate the responsive mechanism, two doses of UV-B radiation (low: 1 W/m2 and high: 5 W/m2) were irradiated for 6 h and 48 h, respectively, and their effects on global metabolism in N. flagelliforme were comprehensively investigated. In this study, we used iTRAQ-based proteomic approach to explore the proteomes of N. flagelliforme, and 151, 172, 124 and 148 differentially expressed proteins were identified under low and high UV-B doses for 6 h and 48 h, respectively. Functional classification analysis showed these proteins were mainly involved in photosynthesis, amino acid metabolism, antioxidant activity and carbohydrate metabolism. Further analysis revealed that UV-B imposed restrictions on primary metabolism including photosynthesis, Calvin cycle, and amino acid metabolism, and cells started defense mechanism through repair of DNA and protein damage, increasing antioxidant activity, and accumulating extracellular polysaccharides to minimize the damage. Moreover, high UV-B dose imposed more severe restrictions and activated stronger defense mechanism compared with low dose. The results would improve the understanding of molecular mechanisms of UV-B-stress adaption in N. flagelliforme.
Assuntos
Nostoc/metabolismo , Nostoc/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Adaptação Biológica/genética , Aminoácidos/metabolismo , Antioxidantes/metabolismo , Metabolismo dos Carboidratos , Fotossíntese , Proteoma/metabolismo , Proteômica/métodosRESUMO
Ultraviolet-B radiation (UVB) reaching the earth's surface has increased due to human-caused stratospheric ozone depletion. Whereas the harmful effects of UVB on aquatic organisms are well studied at the molecular and cellular level, recent studies have also begun to address behavioural changes caused by sublethal amounts of UVB. However, the behavioural consequences of long-term exposure to ecologically relevant UVB levels over several life stages are virtually unknown, particularly with regard to predator-prey behaviour. We found increased predator-inspection behaviour together with a smaller body length in three-spined sticklebacks (Gasterosteus aculeatus) after fish were exposed for about seven months to natural sunlight conditions with enhanced UVB, compared with full siblings exposed to natural sunlight only. The observed change in antipredator behaviour may reflect a direct behavioural response mediated through UVB-induced oxidative stress during development. Alternatively, the smaller body size in UVB-exposed fish may result in an increased inspection effort allowing them to spend more time foraging. Our findings suggest that, within the scope of environmental change, UVB radiation constitutes an important stress factor by eliciting behavioural responses that influence crucial ecological processes, such as predator-prey interactions.
Assuntos
Reação de Fuga/efeitos da radiação , Cadeia Alimentar , Smegmamorpha/fisiologia , Raios Ultravioleta , Animais , Tamanho Corporal , Feminino , Masculino , Smegmamorpha/crescimento & desenvolvimento , Fatores de TempoRESUMO
We previously found that ultraviolet B (UVB) could stimulate the paraventricular nucleus (PVN) with activation the systemic hypothalamic-pituitary- adrenal (HPA) axis. To investigate whether UVB can also stimulate other hypothalamic nuclei, we tested its effect on the proopiomelanocortin (POMC) related signalling system in the arcuate nucleus (ARC) of female C57BL/6 and FVB albino mice. The shaved back skin of the mice was irradiated with either 100 or 400 mJ/cm2 of UVB. After 1, 3, 6 and 12 h, blood and hypothalamus were collected and processed for gene and protein expression, and measurement of α-MSH and ß-endorphin (ß-END) levels. An in situ immunohistochemical examination was performed for melanocortin receptor 4 (MC4R) and POMC-derived α-MSH. The expression of Pomc and MC4R mRNAs was stimulated, whereas that of AgRP was inhibited after exposure to UVB. It was accompanied by an increased number of both α-MSH- and MC4R-immunoreactive neurons in the ARC, and by increased levels of α-MSH and ß-END (both found in the hypothalamus and plasma). This surprising discovery of UVB stimulating the POMC system in the ARC, accompanied by the increased plasma levels of α-MSH and ß-END, paves the way for exciting areas of research on the communication between the skin and the brain, as well as is suggesting a new role for UVB in regulation of body metabolism.
Assuntos
Núcleo Arqueado do Hipotálamo/metabolismo , Pró-Opiomelanocortina/biossíntese , Pele/efeitos da radiação , Raios Ultravioleta , Proteína Relacionada com Agouti/biossíntese , Proteína Relacionada com Agouti/genética , Animais , Metabolismo Basal , Feminino , Regulação da Expressão Gênica/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Pró-Opiomelanocortina/genética , RNA Mensageiro/biossíntese , Receptor Tipo 4 de Melanocortina/biossíntese , Receptor Tipo 4 de Melanocortina/genética , Transdução de Sinais/fisiologia , Organismos Livres de Patógenos Específicos , alfa-MSH/biossíntese , alfa-MSH/sangue , alfa-MSH/genética , beta-Endorfina/biossíntese , beta-Endorfina/sangue , beta-Endorfina/genéticaRESUMO
Glycyrrhizic acid (GA), a natural triterpene, has received attention as an agent that has protective effects against chronic diseases including ultraviolet UV-B-induced skin photodamage. However, the mechanism of its protective effect remains elusive. Here, we used an immortalized human keratinocyte cell line (HaCaT) and a small animal model (BALB/c mice), to investigate the protective effects of GA against UV-B-induced oxidative damage, and additionally, delineated the molecular mechanisms involved in the UV-B-mediated inflammatory and apoptotic response. In the HaCaT cells, GA inhibited the UV-B-mediated increase in intracellular reactive oxygen species (ROS) and down-regulated the release of pro-inflammatory cytokines interleukin (IL)-1α, -1ß and -6, tumor necrosis factor (TNF)-α and prostaglandin E2 (PGE2). GA inhibited UV-B-mediated activation of p38 and JNK MAP kinases, COX-2 expression and nuclear translocation of NF-κB. Furthermore, GA inhibited UV-B-mediated apoptosis by attenuating translocation of Bax from the cytosol to mitochondria, thus preserving mitochondrial integrity. GA-treated HaCaT cells also exhibited elevated antiapoptotic Bcl-2 protein, concomitant with reduced caspase-3 cleavage and decreased PARP-1 protein. In BALB/c mice, topical application of GA on dorsal skin exposed to UV-B irradiation protected against epidermal hyperplasia, lymphocyte infiltration and expression of several inflammatory proteins, p38, JNK, COX-2, NF-κB and ICAM-1. Based on the above findings, we conclude that GA protects against UV-B-mediated photodamage by inhibiting the signalling cascades triggered by oxidative stress, including MAPK/NF-κB activation, as well as apoptosis. Thus, GA has strong potential to be used as a therapeutic/cosmeceutical agent against photodamage.
Assuntos
Anti-Inflamatórios/farmacologia , Ácido Glicirrízico/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos da radiação , Animais , Anti-Inflamatórios/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular , Dermatite/etiologia , Dermatite/prevenção & controle , Avaliação Pré-Clínica de Medicamentos , Ácido Glicirrízico/uso terapêutico , Humanos , Hiperplasia/etiologia , Hiperplasia/prevenção & controle , Metionina/análogos & derivados , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Pele/enzimologia , Sulfóxidos , Raios Ultravioleta/efeitos adversosRESUMO
Apoptosis is an essential physiological process accompanying the development of the central nervous system and human neurogenesis. However, the time scale and the underlying molecular mechanisms are yet poorly understood. Due to this fact, we investigated the functionality and general inducibility of apoptosis in the human neural ReNcell VM progenitor cell line during differentiation and also after exposure to staurosporine (STS) and ultraviolet B (UVB) irradiation. Transmission light microscopy, flow cytometry, and Western-/Immunoblot analysis were performed to compare proliferating and differentiating, in addition to STS- and UVB-treated cells. In particular, from 24 to 72 h post-initiation of differentiation, G0/G1 cell cycle arrest, increased loss of apoptotic cells, activation of pro-apoptotic BAX, Caspase-3, and cleavage of its substrate PARP were observed during cell differentiation and, to a higher extent, after treatment with STS and UVB. We conclude that redundant or defective cells are eliminated by apoptosis, while otherwise fully differentiated cells were less responsive to apoptosis induction by STS than proliferating cells, likely as a result of reduced APAF-1 expression, and increased levels of BCL-2. These data provide the evidence that apoptotic mechanisms in the neural ReNcell VM progenitor cell line are not only functional, but also inducible by external stimuli like growth factor withdrawal or treatment with STS and UVB, which marks this cell line as a suitable model to investigate apoptosis signaling pathways in respect to the differentiation processes of human neural progenitor cells in vitro.
Assuntos
Apoptose/fisiologia , Diferenciação Celular/fisiologia , Células-Tronco Neurais/fisiologia , Neurogênese/fisiologia , Neurônios/fisiologia , Transdução de Sinais/fisiologia , Linhagem Celular , Linhagem Celular Transformada , HumanosRESUMO
BACKGROUND: Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma, typically presents in middle-aged to elderly individuals. OBJECTIVE: We sought to study the demographics, clinicopathologic features, treatment response, and prognosis of patients with biopsy-proven MF diagnosed before 20 years of age. METHODS: Patients were identified from a prospectively collected database for retrospective analysis. RESULTS: Of 1902 patients with MF, 34 had juvenile-onset MF: 41% were stage IA, 56% were stage IB, and 3% were stage IIB at diagnosis. The male to female ratio was 1.1:1. The median age of symptom onset was 9 years (range 3-19 years), with a delay in diagnosis between 1 month and 14 years. Patients primarily presented with hypopigmented (53%), hyperpigmented (29%), and pink-violaceous (41%) patches/plaques. Immunohistochemistry revealed 39% with CD8(+) immunophenotype, 67% of which had hypopigmented lesions. The phototherapy response rate in 21 patients was 81%. All patients who completely responded to narrowband ultraviolet B phototherapy had hypopigmented MF. LIMITATIONS: This is a single cancer center study. CONCLUSION: Juvenile-onset MF presents with early-stage disease with an overrepresentation of hypopigmented MF and CD8(+) immunophenotype. Narrowband ultraviolet B is an effective treatment option for juveniles, especially for those with the hypopigmented variant.
Assuntos
Micose Fungoide , Terapia PUVA/métodos , Neoplasias Cutâneas , Adolescente , Idade de Início , Biópsia , Criança , Pré-Escolar , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Hiperpigmentação/imunologia , Hiperpigmentação/patologia , Hipopigmentação/imunologia , Hipopigmentação/patologia , Imunofenotipagem , Masculino , Micose Fungoide/tratamento farmacológico , Micose Fungoide/imunologia , Micose Fungoide/patologia , Prognóstico , Estudos Retrospectivos , Pele/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Resultado do Tratamento , Terapia Ultravioleta/métodos , Deficiência de Vitamina D/imunologia , Deficiência de Vitamina D/patologia , Adulto JovemRESUMO
BACKGROUND & AIMS: Many determinants of vitamin D status have been well-described, yet supplementation guidelines largely follow a one-size-for-all model and deficiency remains common. We hypothesised that accounting accurately for ultraviolet-B (UVB) radiation and considering interactions could advance understanding of vitamin D status. METHODS: Asian, Black, and White participants from the UK Biobank cohort were included (N = 438,978). The Tropospheric Emission Monitoring Internet Service provided UVB data which we linked to participants' place of residence. UVB dose over 135 days prior to blood draw was weighted and added, yielding cumulative and weighted UVB (CW-D-UVB). The association between 25(OH)D and selected variables was assessed in multivariable linear regression models with and without interactions, stratified by ethnicity. Predictors were ranked using standardised ß-coefficients. RESULTS: Median 25(OH)D differed by ethnicity (Asian: 25.4 nmol/L (10.2 ng/mL), Black: 30.6 nmol/L (12.2 ng/mL), White: 47.9 nmol/L (19.2 ng/mL), p-value < 0.001). CW-D-UVB was strongly associated with 25(OH)D in all ethnicities. It was the most important predictor in White (ßAsian = 0.15, ßBlack = 0.20, ßWhite = 0.35), whereas supplementation was in Asian and Black participants (ßAsian = 0.30, ßBlack = 0.24, ßWhite = 0.21). We identified statistically significant interactions between BMI:supplementation (all), CW-D-UVB:sex (Asian and White), and CW-D-UVB:age (Black and White), and in White population between CW-D-UVB and supplementation, BMI, and cholesterol. CONCLUSION: Vitamin D deficiency was widespread, particularly among non-White individuals. UVB was a strong predictor of 25(OH)D and the effect was modified by other factors. Findings suggest that accurately measured ambient-UVB radiation and interactions could improve 25(OH)D prediction models, and support personalised approaches to vitamin D optimisation.