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1.
J Photochem Photobiol B ; 202: 111704, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31743829

RESUMO

Ultraviolet B (UVB) induces inflammation and causes skin aging. The signs of skin aging, such as wrinkles, discolored spots, loss of skin moisture, and disruption of the skin barrier, are mostly caused by inflammatory signaling among various skin layers. The cells on the outermost surface of the skin are keratinocytes; these cells protect the skin against environmental stress and play an important role in immunomodulation by secreting cytokines in response to environmental stress. In the present study, we found that UVB activates STAT1 to mediate inflammatory signaling, yet STAT1 (S272) and STAT (Y702) shows different responses against UVB exposure. Anhua drak tea is a post-fermented dark tea produced in Anhua and Xinhua country in Hunan province of China. Treatment with 2S,3R-6-methoxycarbonylgallocatechin (MCGE), an epigallocatechin gallate derivative isolated from black tea (Anhua dark tea), effectively suppresses STAT1 activation and inflammatory cytokines, and activates Nrf2 pathway to protect cells from reactive oxygen species production in UVB exposed keratinocyte cells (HaCaT). Interestingly, the effects of MCGE were independent on MAPK signaling pathway. Moreover, MCGE regulates inflammatory cytokines in monocyte-keratinocyte (THP-1, HaCaT) co-culture and macrophage differentiation models. These results suggest that MCGE potentially can be used as a photoprotective agent against UVB-induced inflammatory responses.


Assuntos
Catequina/farmacologia , Protetores contra Radiação/farmacologia , Transdução de Sinais/efeitos dos fármacos , Chá/química , Raios Ultravioleta , Sítios de Ligação , Catequina/análogos & derivados , Catequina/química , Catequina/isolamento & purificação , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/efeitos da radiação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Técnicas de Cocultura , Citocinas/metabolismo , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/efeitos da radiação , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estrutura Terciária de Proteína , Protetores contra Radiação/química , Protetores contra Radiação/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT1/química , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais/efeitos da radiação , Chá/metabolismo
3.
An Bras Dermatol ; 94(4): 434-441, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31644616

RESUMO

BACKGROUND: In-vitro studies showed that Leucine-rich glioma inactivated 3 (LGI3) is a keratinocyte-derived cytokine that stimulates melanin synthesis and is increased after ultra violet B (UVB) irradiation. So, we postulated that LGI3 may be involved in vitiligo aetiopathogenesis and may participate in narrow band ultra violet B (NB-UVB) induced pigmentation in vitiligo. OBJECTIVES: To assess this hypothesis, lesional LGI3 immunohistochemical expression of vitiligo patients before and after NB-UVB phototherapy was studied, and its correlation with repigmentation was evaluated. METHODS: Forty vitiligo patients and 20 age, sex, and skin phenotype-matched controls were enrolled. Patients were treated with NB-UVB thrice weekly for 12 weeks. VASI score was evaluated before and after NB-UVB sessions. For vitiligo patients, baseline LGI3 immunohistochemical staining was estimated, and compared to that of controls and to its post-treatment data in those patients. Results: Baseline LGI3 immunohistochemical studied parameters (expression, intensity, percentage and H score) were significantly lower in vitiligo cases than controls (p=0.003, 0.013, 0.001 and 0.001 respectively). After 12 weeks of NB-UVB phototherapy, these LGI3 immunohistochemical parameters were up-regulated and became comparable to that of controls (p >0.05 for all). There was a significant positive correlation between the improvement of both VASI score and LGI3 H score mean values (r=-0.349 , p=0.027). STUDY LIMITATIONS: Small number of investigated subjects. CONCLUSIONS: Decreased LGI3 protein may play an active role in vitiligo pathogenesis and its up-regulation after NB-UVB phototherapy, may actively participate in NB-UVB photo-induced melanogenesis.


Assuntos
Citocinas/análise , Proteínas/análise , Terapia Ultravioleta/métodos , Vitiligo/patologia , Vitiligo/radioterapia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Feminino , Humanos , Imuno-Histoquímica , Queratinócitos/efeitos da radiação , Masculino , Melanócitos/efeitos da radiação , Pessoa de Meia-Idade , Valores de Referência , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
4.
Radiat Res ; 192(4): 410-421, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31390312

RESUMO

Radiation-induced acute skin injury and consequent fibrosis are common complications of cancer radiotherapy and radiation accidents. Stromal cell-derived factor-1α (SDF-1α) and its receptor, CXC chemokine receptor 4 (CXCR4) have been shown to be involved in multiple cellular events. However, the role of SDF-1α/CXCR4 axis in radiation-induced acute injury and fibrosis of skin has not been reported. In this study, we found that the expression of SDF-1α and CXCR4 was significantly increased in irradiated skin tissues of humans, monkeys and rats, compared to their nonirradiated counterparts. Mice with keratinocyte-specific ablation of CXCR4 showed less severe skin damage than wild-type mice after receiving a 35 Gy dose of radiation. Consistently, subcutaneous injection of AMD3100, an FDA approved SDF-1α/CXCR4 inhibitor, attenuated skin injury and fibrosis induced by exposure to radiation in a rat model. Mechanically, the SDF-1α/CXCR4 axis promotes pro-fibrotic TGF-b/Smad signaling through the PI3K-MAPK signaling cascade in human keratinocyte HaCaT cells and skin fibroblast WS1 cells. AMD3100 inhibited Smad2 nuclear translocation and transcriptional activity of Smad2/3 induced by radiation, which suppressed the pro-fibrotic TGF-b/Smad signaling pathway activated by exposure. Taken together, these findings demonstrate the involvement of SDF-1α/CXCR4 axis in radiation-induced acute injury and fibrosis of skin, and indicate that AMD3100 would be an effective countermeasure against these diseases.


Assuntos
Quimiocina CXCL12/metabolismo , Lesões por Radiação/metabolismo , Receptores CXCR4/metabolismo , Pele/patologia , Pele/efeitos da radiação , Animais , Fibrose , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Técnicas de Inativação de Genes , Compostos Heterocíclicos/farmacologia , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos da radiação , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Lesões por Radiação/patologia , Ratos , Receptores CXCR4/deficiência , Receptores CXCR4/genética , Pele/lesões , Pele/metabolismo , Proteína Smad2/metabolismo , Fator de Crescimento Transformador beta/metabolismo
5.
Mar Drugs ; 17(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374828

RESUMO

Excessive exposure to ultraviolet (UV) radiation is the main risk factor to develop skin pathologies or cancer because it encourages oxidative condition and skin inflammation. In this sense, strategies for its prevention are currently being evaluated. Natural products such as carotenoids or polyphenols, which are abundant in the marine environment, have been used in the prevention of oxidative stress due to their demonstrated antioxidant activities. Nevertheless, the anti-inflammatory activity and its implication in photo-prevention have not been extensively studied. Thus, we aimed to evaluate the combination of fucoxanthin (FX) and rosmarinic acid (RA) on cell viability, apoptosis induction, inflammasome regulation, and anti-oxidative response activation in UVB-irradiated HaCaT keratinocytes. We demonstrated for the first time that the combination of FX and RA (5 µM RA plus 5 µM FX, designated as M2) improved antioxidant and anti-inflammatory profiles in comparison to compounds assayed individually, by reducing UVB-induced apoptosis and the consequent ROS production. Furthermore, the M2 combination modulated the inflammatory response through down-regulation of inflammasome components such as NLRP3, ASC, and Caspase-1, and the interleukin (IL)-1ß production. In addition, Nrf2 and HO-1 antioxidant genes expression increased in UVB-exposed HaCaT cells pre-treated with M2. These results suggest that this combination of natural products exerts photo-protective effects by down-regulating NRLP3-inflammasome and increasing Nrf2 signalling pathway.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Cinamatos/farmacologia , Depsídeos/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Xantofilas/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Sinergismo Farmacológico , Humanos , Inflamassomos/efeitos dos fármacos , Inflamassomos/imunologia , Inflamassomos/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Queratinócitos/efeitos da radiação , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Transdução de Sinais/efeitos da radiação , Pele/citologia , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Envelhecimento da Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos
6.
Artif Cells Nanomed Biotechnol ; 47(1): 3548-3558, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31456420

RESUMO

The extensive relevance of nanoparticles arouses the requirement for manufacturing although the predictable technique are frequently perilous and energy saving. In the current study, zinc oxide nanoparticles manufactured from Allium cepa avert UVB radiation interceded irritation in human epidermal keratinocytes (HaCaT cells). In the current study, the zinc oxide nanoparticles (ZnO-NPs) was synthesized from the extract of A. cepa. The optimized ZnO-NPs hence attained and was enumerated and exemplified by UV visible spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), scanning electron microscope (SEM) and EDAX impending analysis. In addition, amalgamated ZnO-NPs were experienced for cell viability (MTT), formation of reactive oxygen species (ROS), apoptosis, and antioxidant and lipid peroxidation (TBARS) levels. Also, we explored the effect of A. cepa ZnO-NPs in molecular level by evaluating the inflammatory and apoptotic markers, in which ZnO-NPs reinstated the interleukins 6, 10 and related signaling molecules like iNOS, COX-2 levels. Ultimately, ZnO-NPs induce apoptotic markers (Bax, Bcl-2) and also recommended that ZnO-NPs might aggravate cancer cell apoptosis in HaCaT cells.


Assuntos
Epiderme/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Cebolas/metabolismo , Raios Ultravioleta/efeitos adversos , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Animais , Linhagem Celular , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Inflamação/prevenção & controle , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Espaço Intracelular/efeitos da radiação , Queratinócitos/citologia , Queratinócitos/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Protetores contra Radiação/química , Protetores contra Radiação/metabolismo , Protetores contra Radiação/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Óxido de Zinco/metabolismo
7.
J Steroid Biochem Mol Biol ; 195: 105449, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31470109

RESUMO

The skin is a unique site in the human body that has the capacity to synthesize the active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), from 7-dehydrocholesterol (7DHC) upon UV irradiation. Keratinocytes express both 25-hydroxylase (CYP27A1 and CYP2R1) and 1α-hydroxylase (CYP27B1), critical enzymes involved in active vitamin D synthesis. Here, we investigated the effect of skin-derived 1α,25(OH)2D3, synthesized purely within the keratinocytes, on MMP-1 expression. Treatment of human epidermal keratinocytes with 1α,25(OH)2D3, but not 7DHC or 25OHD3, significantly increased MMP-1 expression. UV irradiation increases 1α,25(OH)2D3 levels, and ketoconazole inhibits UV-induced production of 1α,25(OH)2D3. Upregulation of MMP-1 by UV was reversed by inhibition of 1α,25(OH)2D3 synthesis using ketoconazole or CYP27B1 siRNA. In keratinocytes, 7DHC is a substrate for both cholesterol and 1α,25(OH)2D3 synthesis. We demonstrated that UV irradiation leads to decreased expression of DHCR7 (7-dehydrocholesterol reductase), the enzyme that converts 7DHC to cholesterol. Inhibition of DHCR7 with its inhibitor BM15766 decreased cholesterol synthesis and increased UV-induced MMP-1 expression, which was attenuated by ketoconazole. These findings suggest that UV-induced reduction of DHCR7 leads to a decrease in cholesterol synthesis, thereby increasing 7DHC availability for 1α,25(OH)2D3 production, which enhances MMP-1 expression. Finally, UV irradiation in human skin in vivo significantly increased CYP27B1 mRNA and decreased DHCR7 mRNA expression. Taken together, we demonstrate here that skin-derived 1α,25(OH)2D3 significantly increases MMP-1 expression in human keratinocytes, a previously unappreciated function of 1α,25(OH)2D3. Moreover, UV irradiation upregulates the enzyme CYP27B1, which leads to 1α,25(OH)2D3 synthesis, but downregulates the cholesterol-producing enzyme DHCR7, both of which collectively lead to increased MMP-1 expression in human keratinocytes. This pathway may be exploited to develop a novel cutaneous anti-aging agent that blocks local cutaneous 1α,25(OH)2D3 synthesis.


Assuntos
Desidrocolesteróis/metabolismo , Queratinócitos/efeitos da radiação , Metaloproteinase 1 da Matriz/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta , Vitamina D/análogos & derivados , Vitaminas/metabolismo , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Adulto , Células Cultivadas , Humanos , Queratinócitos/metabolismo , Pessoa de Meia-Idade , Pele/metabolismo , Vitamina D/metabolismo
8.
Molecules ; 24(17)2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31454971

RESUMO

Quercus mongolica Fisch. ex Ledeb. (QM) has been used as an oriental traditional medicine to relieve hemorrhoids, fever, and enteritis. We screened the inhibitory activities of the extracts and compounds (1-6) isolated from QM on the production of inflammatory cytokines and chemokines to evaluate their anti-inflammatory activities. Further, we evaluated the expression levels of cytokines, chemokines, and immune factors on pedunculagin (PC, 1), which was selected from isolated compounds (1-6) because of its potential anti-inflammation effect. Additionally, we evaluated whether the inflammation mitigation effects of PC (1) following UVB exposure in keratinocytes occurred because of nuclear factor (NF)-κB and signal transducer and activator of transcription (STAT)/Janus kinase (JAK) activation. PC (1) remarkably suppressed interleukin (IL)-6, IL-10, IL-13, and monocyte chemoattractant protein-1 (MCP-1) mRNA expression and reduced the mRNA expression level of Cyclooxygenase-2 (COX-2) and also reduced the phosphorylation of p38 mitogen-activated protein kinases (p38), c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) in a concentration-dependent manner.


Assuntos
Anti-Inflamatórios/farmacologia , Queratinócitos/citologia , Fenóis/farmacologia , Quercus/química , Taninos/farmacologia , Anti-Inflamatórios/química , Linhagem Celular , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Avaliação Pré-Clínica de Medicamentos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Lipopolissacarídeos/efeitos adversos , NF-kappa B , Fenóis/química , Fosforilação , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Taninos/química , Raios Ultravioleta/efeitos adversos
9.
Int J Mol Sci ; 20(16)2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31426336

RESUMO

Reactive oxygen species (ROS) are generated from diverse cellular processes or external sources such as chemicals, pollutants, or ultraviolet (UV) irradiation. Accumulation of radicals causes cell damage that can result in degenerative diseases. Antioxidants remove radicals by eliminating unpaired electrons from other molecules. In skin health, antioxidants are essential to protect cells from the environment and prevent skin aging. (-)-Epigallocatechin-3-(3″-O-methyl) gallate (3″Me-EGCG) has been found in limited oolong teas or green teas with distinctive methylated form, but its precise activities have not been fully elucidated. In this study, we examined the antioxidant roles of 3″Me-EGCG in keratinocytes (HaCaT cells). 3″Me-EGCG showed scavenging effects in cell and cell-free systems. Under H2O2 exposure, 3″Me-EGCG recovered cell viability and increased the expression of heme oxygenase 1 (HO-1). Under ultraviolet B (UVB) and sodium nitroprusside (SNP) exposure, 3″Me-EGCG protected keratinocytes and regulated the survival protein AKT1. By regulating the AKT1/NF-κB pathway, 3″Me-EGCG augmented cell survival and proliferation in HaCaT cells. These results indicate that 3″Me-EGCG exhibits antioxidant properties, resulting in cytoprotection against various external stimuli. In conclusion, our findings suggest that 3″Me-EGCG can be used as an ingredient of cosmetic products or health supplements.


Assuntos
Antioxidantes/farmacologia , Catequina/análogos & derivados , Citoproteção/efeitos dos fármacos , Ácido Gálico/análogos & derivados , Queratinócitos/efeitos dos fármacos , Antioxidantes/química , Catequina/química , Catequina/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Citoproteção/efeitos da radiação , Ácido Gálico/química , Ácido Gálico/farmacologia , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Protetores contra Radiação/química , Protetores contra Radiação/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Raios Ultravioleta/efeitos adversos
10.
An. bras. dermatol ; 94(4): 434-441, July-Aug. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1038295

RESUMO

Abstract: Background: In-vitro studies showed that Leucine-rich glioma inactivated 3 (LGI3) is a keratinocyte-derived cytokine that stimulates melanin synthesis and is increased after ultra violet B (UVB) irradiation. So, we postulated that LGI3 may be involved in vitiligo aetiopathogenesis and may participate in narrow band ultra violet B (NB-UVB) induced pigmentation in vitiligo. Objectives: To assess this hypothesis, lesional LGI3 immunohistochemical expression of vitiligo patients before and after NB-UVB phototherapy was studied, and its correlation with repigmentation was evaluated. Methods: Forty vitiligo patients and 20 age, sex, and skin phenotype-matched controls were enrolled. Patients were treated with NB-UVB thrice weekly for 12 weeks. VASI score was evaluated before and after NB-UVB sessions. For vitiligo patients, baseline LGI3 immunohistochemical staining was estimated, and compared to that of controls and to its post-treatment data in those patients. Results: Baseline LGI3 immunohistochemical studied parameters (expression, intensity, percentage and H score) were significantly lower in vitiligo cases than controls (p=0.003, 0.013, 0.001 and 0.001 respectively). After 12 weeks of NB-UVB phototherapy, these LGI3 immunohistochemical parameters were up-regulated and became comparable to that of controls (p >0.05 for all). There was a significant positive correlation between the improvement of both VASI score and LGI3 H score mean values (r=-0.349 , p=0.027). Study limitations: Small number of investigated subjects. Conclusions: Decreased LGI3 protein may play an active role in vitiligo pathogenesis and its up-regulation after NB-UVB phototherapy, may actively participate in NB-UVB photo-induced melanogenesis.


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Terapia Ultravioleta/métodos , Vitiligo/patologia , Vitiligo/radioterapia , Proteínas/análise , Citocinas/análise , Valores de Referência , Fatores de Tempo , Índice de Gravidade de Doença , Imuno-Histoquímica , Estudos de Casos e Controles , Queratinócitos/efeitos da radiação , Resultado do Tratamento , Estatísticas não Paramétricas , Melanócitos/efeitos da radiação
11.
Biol Pharm Bull ; 42(9): 1524-1531, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31270288

RESUMO

UVB radiation changes several photoaging pathway in the body, thereby prompting skin injury. Besides, chronic UVB radiation leads to photoaging, sustained immunosuppression, and photocarcinogenesis. We investigated the protective effect of Timosaponin AIII (TA-III), a naturally occurring steroidal saponin separated from Anemarrhena asphodeloides, against UVB-induced invasive properties of human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDF). No cytotoxicity was observed up to 50 nM concentration of TA-III. Similarly, TA-III inhibited UVB-induced cyclooxygenase-2 (COX-2), matrix metalloproteinase-9 (MMP-9) transcription level and protein expression in a dose-dependent manner at non-cytotoxic dose. Further, TA-III decreased UVB-induced invasion in primary skin cells. Additionally, TA-III suppressed UVB-stimulates mitogen-activated protein kinase (MAPK) signaling, activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB) activation, thereby preventing the overexpression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and COX-2 in human epidermal keratinocytes cells. Furthermore, TA-III prevented UVB-mediated formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and activation of DNA repair enzymes and, cell cycle arrest genes like as proliferating cell nuclear antigen (PCNA), structural maintenance of chromosomes protein 1 (SMC1). This results support that understanding into the molecular action of TA-III, which can be useful for developing photoprotective agents.


Assuntos
Anti-Inflamatórios/farmacologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Saponinas/farmacologia , Esteroides/farmacologia , Raios Ultravioleta , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Ciclo-Oxigenase 2/genética , Dano ao DNA , Humanos , Queratinócitos/metabolismo , Metaloproteinase 9 da Matriz/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Protetores contra Radiação/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição AP-1/metabolismo
12.
Int J Mol Sci ; 20(14)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340560

RESUMO

BACKGROUND: Due to current antibiotic resistance worldwide, there is an urgent need to find new alternative antibacterial approaches capable of dealing with multidrug-resistant pathogens. Most recent studies have demonstrated the antibacterial activity and non-cytotoxicity of carbon nanomaterials such as graphene oxide (GO) and carbon nanofibers (CNFs). On the other hand, light-emitting diodes (LEDs) have shown great potential in a wide range of biomedical applications. METHODS: We investigated a nanotechnological strategy consisting of GO or CNFs combined with light-emitting diod (LED) irradiation as novel nanoweapons against two clinically relevant Gram-positive multidrug-resistant pathogens: methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE). The cytotoxicity of GO and CNFs was studied in the presence of human keratinocyte HaCaT cells. RESULTS: GO or CNFs exhibited no cytotoxicity and high antibacterial activity in direct contact with MRSE and MRSA cells. Furthermore, when GO or CNFs were illuminated with LED light, the MRSE and MRSA cells lost viability. The rate of decrease in colony forming units from 0 to 3 h, measured per mL, increased to 98.5 ± 1.6% and 95.8 ± 1.4% for GO and 99.5 ± 0.6% and 99.7 ± 0.2% for CNFs. CONCLUSIONS: This combined antimicrobial approach opens up many biomedical research opportunities and provides an enhanced strategy for the prevention and treatment of Gram-positive multidrug-resistant infections.


Assuntos
Antibacterianos/farmacologia , Grafite/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos da radiação , Nanoestruturas/química , Nanotubos de Carbono/química , Staphylococcus epidermidis/efeitos da radiação , Linhagem Celular , Sobrevivência Celular/efeitos da radiação , Técnicas de Cocultura , Relação Dose-Resposta à Radiação , Humanos , Queratinócitos/citologia , Queratinócitos/fisiologia , Queratinócitos/efeitos da radiação , Luz , Resistência a Meticilina/efeitos da radiação , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos da radiação , Nanoestruturas/ultraestrutura , Nanotubos de Carbono/ultraestrutura , Fototerapia/métodos , Staphylococcus epidermidis/crescimento & desenvolvimento
13.
Oxid Med Cell Longev ; 2019: 2352079, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31346357

RESUMO

Radiation-induced oral mucositis (RIOM) is one of the most common side effects of radiotherapy in cancer patients, especially in almost all head and neck cancer patients. It presents as severe pain and ulceration. The development of RIOM is composed of five stages: initiation, primary damage response, signal amplification, ulceration, and healing. However, the key regulators involved in the RIOM pathogenesis remain largely unknown. In this study, we reveal a novel role of miR-200c, a member of the miR-200 family, in modulating RIOM pathogenesis. Using a mouse model mimicking RIOM, we found that the miR-200 family numbers (miR-141, miR-200a, miR-200b, and miR-200c) except miR-429 were significantly induced during the RIOM formation. Besides, in RIOM mice, miR-200c expression level was also increased dramatically in the normal human keratinocytes (NHKs) after irradiation. Knockdown of miR-200c expression with miR-200c-3p-shRNA significantly reduced senescence phenotype and enhanced cell proliferation in NHKs after irradiation. The generation of reactive oxygen species (ROS) and p47 enzyme involved in ROS production was increased after irradiation but both were markedly reduced in NHKs by miR-200c inhibition. Knockdown of miR-200c expression in NHKs increased DNA double-strand break repair after irradiation compared with control NHKs. Furthermore, miR-200c inhibition repressed the production of proinflammatory cytokines (TGF-ß, TNF-α, and IL-1α) via inhibiting NF-κB and Smad2 activation in NHKs exposed to IR. Additionally, miR-200c inhibition promoted NHK migration and increased the expression of molecules that regulate epithelial to mesenchymal transition, including Snail, Vimentin, Zeb1, and Bmi-1. These results not only identify the key role of miR-200c in the pathogenesis of RIOM but also provide a novel therapeutic target to treat RIOM.


Assuntos
MicroRNAs/metabolismo , Estomatite/etiologia , Animais , Movimento Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Senescência Celular/efeitos da radiação , Citocinas/biossíntese , Reparo do DNA , Humanos , Queratinócitos/metabolismo , Queratinócitos/patologia , Queratinócitos/efeitos da radiação , Camundongos , MicroRNAs/genética , Lesões Experimentais por Radiação/etiologia , Lesões Experimentais por Radiação/genética , Lesões Experimentais por Radiação/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estomatite/genética , Estomatite/metabolismo , Estomatite/patologia
14.
Plast Reconstr Surg ; 144(2): 347-356, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31348342

RESUMO

BACKGROUND: Hyperpigmentation following ultraviolet irradiation has cosmetic concerns. Botulinum toxin type A can favorably affect skin pigmentation. However, the mechanism of skin pigmentation is unclear. METHODS: In vitro, human epidermal melanocytes were co-cultured with human keratinocytes. After cells were treated with botulinum toxin type A, cell morphology, proliferation, and dendricity were analyzed, and immunofluorescence, tyrosinase activity, and melanin contents were determined. To evaluate the effect of botulinum toxin type A on ultraviolet B-irradiated mouse skin, ultraviolet B alone was applied to one side of the back of each mouse as a control, whereas ultraviolet B plus injection of botulinum toxin type A was applied to the contralateral side. Skin pigmentation, histology, and the number of dihydroxyphenylalanine-positive melanocytes were evaluated. The L* colorimeter value was measured. Enzyme-linked immunosorbent assay determinations of basic fibroblast growth factor, interleukin-1 alpha, and prostaglandin E2 were performed. RESULTS: Immunohistochemical staining revealed botulinum toxin type A in the cytoplasm of melanocytes and in the positive control. In vitro, melanocyte dendricity and melanin contents were decreased slightly but significantly (p < 0.05) after botulinum toxin type A treatment. In vivo, botulinum toxin type A suppressed skin pigmentation. The number of dihydroxyphenylalanine-positive melanocytes was also significantly lower than in the control side. Tyrosinase activity and melanin content were also significantly reduced (p < 0.05). Botulinum toxin type A also significantly reduced the amounts of basic fibroblast growth factor, interleukin-1 alpha, and prostaglandin E2 (all p < 0.05). CONCLUSION: Botulinum toxin type A can suppress epidermal melanogenesis through both direct and indirect mechanisms.


Assuntos
Toxinas Botulínicas Tipo A/farmacologia , Hiperpigmentação/prevenção & controle , Protetores contra Radiação/farmacologia , Pigmentação da Pele/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos , Animais , Proliferação de Células , Células Cultivadas , Citocinas/metabolismo , Di-Hidroxifenilalanina/metabolismo , Epiderme/efeitos da radiação , Humanos , Injeções Intraperitoneais , Queratinócitos/citologia , Queratinócitos/efeitos da radiação , Masculino , Melaninas/metabolismo , Melanócitos/metabolismo , Melanócitos/efeitos da radiação , Camundongos Pelados , Monofenol Mono-Oxigenase/metabolismo , Fotometria , Pigmentação da Pele/efeitos da radiação
15.
Int J Biol Macromol ; 137: 1002-1012, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31252020

RESUMO

Extracellular polysaccharide (EPS) produced by Pantoea agglomerans was purified for structural analysis and anti-UVB activity evaluation. The results showed that the EPS comprised of mannose and glucose in a ratio of 3:2. The molecular weight of EPS was estimated as 679 KDa. Fourier transform infrared spectrometry (FT-IR) showed that the EPS was composed of d-furanose without any substituent group. The structure of the EPS could be deduced as a repeated pentasaccharide arranged of three mannose molecules and two glucose molecules according to electrospray ionization mass spectrometry (ESI-MS) analysis and results mentioned above. The results also showed that the EPS attenuated UVB-induced cytotoxicity which was verified by morphology feature assay, down-regulated the expression of phosphor-JNK and active caspase3 significantly through MAPK pathway in UVB-irradiated HaCaT cells, and therefore protected the cells from apoptosis which could be identified by the lower apoptosis rate at low dose of UVB ray. In conclusion, the EPS as a macromolecule arranged by repeated pentasaccharide could protect HaCaT keratinocytes from UVB irradiation injury effectively, and the underlying mechanism may involve MAPK signaling pathway which contribute to apoptotic cell death. However, further studies on efficacy of the EPS in vivo are needed to determine.


Assuntos
Espaço Extracelular/química , Pantoea/citologia , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/farmacologia , Protetores contra Radiação/química , Protetores contra Radiação/farmacologia , Raios Ultravioleta/efeitos adversos , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Peso Molecular , Monossacarídeos/análise , Polissacarídeos Bacterianos/isolamento & purificação , Protetores contra Radiação/isolamento & purificação
16.
Nutrients ; 11(6)2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31207929

RESUMO

It is well known that ultraviolet light activates mitogen-activated protein (MAP) kinase by increasing the reactive oxygen species (ROS) in the body, enhancing activating protein 1(AP-1) complexes (c-Jun and c-Fos), increasing matrix metalloproteinases (MMPs) and degrading collagen and elastin. In this study, we confirmed that polyphenolic rich Spatholobus suberectus (SS) stem extracts suppressed ultraviolet (UV)-induced photo-aging. The major active components of SS stem extracts were identified as gallic acid, catechin, vanillic acid, syringic acid and epicatechin. The aqueous and ethanolic extracts of the stem of SS (SSW and SSE, respectively) significantly reduced the elastase enzyme activity. Moreover, both extracts were suppressed the ROS generation and cellular damage induced by UVB in HaCaT cells. Our results also revealed that SSE could regulate the expression of MMPs, tissue inhibitor of matrix metalloproteinase (TIMP)-1, collagen type I alpha 1 (COL1A1), elastin (ELN) and hyaluronan synthase 2 (HAS2) at their transcriptional and translational level. Furthermore, SSE was blocked the UVB-induced phosphorylation of mitogen-activated protein kinases (MAPKs), nuclear factor-kappa B (NF-κB) and c-Jun. Moreover, combination of syringic acid, epicatechin and vanillic acid showed strong synergistic effects on elastase inhibition activity, in which the combination index (CI) was 0.28. Overall, these results strongly suggest that the polyphenolics of SSE exert anti-ageing potential as a natural biomaterial to inhibit UVB-induced photo-aging.


Assuntos
Fabaceae/química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Extratos Vegetais/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Fator de Transcrição AP-1/metabolismo , Linhagem Celular , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Metaloproteinases da Matriz/metabolismo , Caules de Planta/química , Polifenóis/farmacologia , Raios Ultravioleta
17.
J Photochem Photobiol B ; 197: 111518, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31202076

RESUMO

Disclosure of ultraviolet (UV) radiation is the key feature from environment to cause redness of the skin, inflammation, photoaging and skin cancer. 6-Shogaol, a spicy compound secluded from ginger, which shows anti-inflammatory effects. Present study was demonstrated the role of 6-Shogaol on UVB induced oxidative stress and photoaging signaling in human epidermal keratinocytes (HaCaT cells). In this study, UVB-irratiation (180 mJ/cm2) significantly elevated the intracellular ROS levels, depletion of antioxidants resulted in apoptotic HaCaT cells. MAPKs signaling are concerned in oxidative stress; these signaling events are measured as differentiation. We found that 6-shogaol prevents over expression of MAPKs (ERK1, JNK1 & p38), in disclosure of UVB in HaCaT cells. Moreover, 6-shogaol infringed Bax and Bcl-2 in which 20 µg 6-shogaol influenced apoptosis in HaCaT cells by investigating augmented appearance of Bax and condensed appearance of Bcl-2 in contrast to control HaCaT cells. These results suggest that 6-shogaol could be a successful healing agent provides fortification against UVB-induced provocative and oxidative skin reimbursement.


Assuntos
Catecóis/farmacologia , Gengibre/química , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Raios Ultravioleta , Apoptose/efeitos dos fármacos , Catecóis/química , Catecóis/uso terapêutico , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Gengibre/metabolismo , Humanos , Inflamação/metabolismo , Inflamação/prevenção & controle , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos da radiação , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína X Associada a bcl-2/metabolismo
18.
Lasers Med Sci ; 34(9): 1725-1734, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31154598

RESUMO

Photobiomodulation therapy (PBMT) has been widely used for the promotion of tissue repair. Despite these therapeutic benefits, in some cases, PBMT appears to be unsuccessful, and the strongest hypothesis is that this failure is due to inadequate light dosimetry and wavelengths. The objective of the present critical review was to evaluate the effects of PBMT on cultured keratinocytes using blue, red, or near-infrared light categorized into arbitrary ranges of energy density (0.1-5.0, 5.1-10.0, 10.1-15.0, and over 15.0 J/cm2). The electronic searches were conducted in PubMed, Web of Science, Scopus and LILACS databases, and included LASER or LED devices. A total of 55 articles evaluating the effects of PBMT on cell viability, proliferation, migration, and cytokine and growth factor production were included. Overall, the studies failed to provide detailed information about light dosimetry or detailed experimental conditions. The vast majority of the energy densities tested produced unmodified results regardless of the wavelength applied. However, it was possible to observe that red and near-infrared light had more stimulatory effects than blue light. In addition, for all parameters analyzed, favorable outcomes were mostly obtained in the range of 0.1-5.0 J/cm2. The less explored energy densities were within the 10.1-15.0 J/cm2 range. Energy densities above 15.0 J/cm2 were ineffective or tended to cause cell death. The heterogeneity of the data does not allow us to define a PBMT range setting protocol that would have beneficial effects on keratinocytes.


Assuntos
Queratinócitos/citologia , Queratinócitos/efeitos da radiação , Terapia com Luz de Baixa Intensidade , Células Cultivadas , Citocinas/biossíntese , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese
19.
Mol Med Rep ; 20(1): 763-770, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115540

RESUMO

Derivatives of caffeoylquinic acid (CQA) have been studied and reported as potent bioactive molecules possessing various health benefits including antioxidant and anti­inflammatory activities. In the present study, the protective effect of 3,5­dicaffeoyl­epi­quinic acid (DCEQA) isolated from Atriplex gmelinii on UVB­induced damages was investigated in human HaCaT keratinocytes. The effect of DCEQA against UVB­induced oxidative stress­mediated damages was determined measuring its ability to alleviate UVB­induced elevation of oxidative stress, proinflammatory response and antioxidant enzyme suppression through nuclear factor­like 2 (Nrf2). Treatment with DCEQA hindered the generation of intracellular reactive oxygen species. Increased levels of proinflammatory cytokines TNF­α, COX­2, IL­6 and IL­1ß following UVB exposure were suppressed by the introduction of DCEQA. Additionally, DCEQA upregulated the mRNA and protein expression of antioxidant enzymes superoxide dismutase­1 and heme oxygenase­1 which were inhibited under UVB irradiation. Antioxidant enzyme regulation transcription factor Nrf2 was also upregulated in the presence of DCEQA. These results suggest that DCEQA prevents photoaging via protection of keratinocytes from UVB irradiation by ameliorating the oxidative stress and pro­inflammatory response.


Assuntos
Queratinócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ácido Quínico/análogos & derivados , Envelhecimento da Pele/efeitos dos fármacos , Antioxidantes/farmacologia , Linhagem Celular , Heme Oxigenase-1/genética , Humanos , Queratinócitos/efeitos da radiação , Fator 2 Relacionado a NF-E2/genética , Ácido Quínico/farmacologia , Espécies Reativas de Oxigênio , Envelhecimento da Pele/genética , Envelhecimento da Pele/efeitos da radiação , Superóxido Dismutase/genética , Fator de Necrose Tumoral alfa/genética , Raios Ultravioleta
20.
Molecules ; 24(9)2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31035502

RESUMO

The application of natural plant extracts in UV-protection is popular and intensively studied. Silymarin (from Silibum marianum), a naturally occurring polyphenol, has recently received attention due to its antioxidant, anti-inflammatory and anti-apoptotic effects. However, its role in the UV-mediated keratinocyte cell response is still controversial. In this study, we investigated the effects of Silibum marianum extracts with different origins and formulations on UVA-exposed HaCaT keratinocytes in vitro. Our results show, that silymarin treatment caused an inverse dose-dependent photosensitivity relationship (at higher doses, a decrease in cell viability and ROS production) after UVA exposure. The attenuation of the UVA-induced ROS generation after silymarin treatment was also observed. Moreover, silymarin pre-treatment increased the cyclobutane pyrimidine dimer photolesions in keratinocytes after UVA exposure. These results indicated the dual role of silymarin in UVA-exposed keratinocytes. It scavenges ROS but still induces phototoxicity. Based on our results dermatological applications of silymarin and related compounds should be considered very carefully.


Assuntos
Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Silimarina/química , Silimarina/farmacologia , Raios Ultravioleta , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Humanos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Raios Ultravioleta/efeitos adversos
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