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1.
Photochem Photobiol Sci ; 20(10): 1299-1307, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34559384

RESUMO

PUVA is a treatment that combines oral methoxypsoralen (8-MOP) with ultraviolet radiation A (UVA). It is used for severe psoriasis and the early stages of T-cell lymphoma. X-rays are an effective treatment for skin cancers. Both treatments are in higher doses used to treat skin malignancies and simultaneously increase the risk of keratinocyte cancer. The main objective of this study was to test whether a few PUVA or X-ray treatments could delay the development of ultraviolet radiation (UVR)-induced skin tumors in a well-established hairless mouse model. Three groups of immunocompetent mice (total, N = 75) were included in the study. All groups were UVR-exposed during the study period. In addition, one group was treated with PUVA and another group was treated with X-rays at days 45, 52, 90 and 97. A control group was treated with UVR only. We recorded when the first, second and third skin tumors were induced in each mouse. Skin tumors developed significantly earlier in both the PUVA and X-ray groups (median, 188 days) than in the control mice (median, 215 days; p < 0.001). Therefore, a few X-ray and PUVA treatments both significantly accelerated the development of skin tumors in hairless mice, compared to UVR controls. Neither treatment showed a delay of UVR-induced skin tumors and caution should be exercised before applying these treatments to sun-damaged skin.


Assuntos
Metoxaleno/efeitos adversos , Neoplasias Cutâneas/etiologia , Raios Ultravioleta , Animais , Hospedeiro Imunocomprometido , Estimativa de Kaplan-Meier , Metoxaleno/química , Metoxaleno/farmacologia , Camundongos , Camundongos Pelados , Neoplasias Induzidas por Radiação/etiologia , Pele/patologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Pigmentação da Pele/efeitos dos fármacos , Pigmentação da Pele/efeitos da radiação , Raios X
2.
Int J Mol Sci ; 22(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200222

RESUMO

Collagen hydrolysates have been suggested as a favorable antiaging modality in skin photoaged by persistent exposure to ultraviolet radiation (UV). The current study evaluated the beneficial effect of collagen hydrolysates (fsCH) extracted from Pangasius hypophthalmus fish skin on wrinkle formation and moisture preservation in dorsal skin of hairless mice challenged with UV-B. Inter-comparative experiments were conducted for anti-photoaging among fsCH, retinoic acid (RA), N-acetyl-D-glucosamine (NAG), and glycine-proline-hydroxyproline (GPH). Treating human HaCaT keratinocytes with 100-200 µg/mL fsCH reciprocally ameliorated the expression of aquaporin 3 (AQP3) and CD44 deranged by UV-B. The UV-B-induced deep furrows and skin thickening were improved in parched dorsal skin of mice supplemented with 206-412 mg/kg fsCH as well as RA and GPH. The UV-B irradiation enhanced collagen fiber loss in the dorsal dermis, which was attenuated by fsCH through enhancing procollagen conversion to collagen. The matrix metalloproteinase expression by UV-B in dorsal skin was diminished by fsCH, similar to RA and GPH, via blockade of collagen degradation. Supplementing fsCH to UV-B-irradiated mice decreased transepidermal water loss in dorsal skin with reduced AQP3 level and restored keratinocyte expression of filaggrin. The expression of hyaluronic acid synthase 2 and hyaluronidase 1 by UV-B was remarkably ameliorated with increased production of hyaluronic acid by treating fsCH to photoaged mice. Taken together, fsCH attenuated photoaging typical of deep wrinkles, epidermal thickening, and skin water loss, like NAG, RA, or GPH, through inhibiting collagen destruction and epidermal barrier impairment.


Assuntos
Colágeno/farmacologia , Proteínas na Dieta/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Dermatopatias/tratamento farmacológico , Pele/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos , Animais , Masculino , Camundongos , Camundongos Pelados , Pele/patologia , Pele/efeitos da radiação , Envelhecimento da Pele/patologia , Envelhecimento da Pele/efeitos da radiação , Dermatopatias/etiologia , Dermatopatias/patologia
3.
J Med Food ; 24(6): 606-616, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34077675

RESUMO

Overexposure to ultraviolet B (UVB) irradiation induces photoaging that is characterized by the formation of wrinkles and loss of skin elasticity. To understand the mechanism of action of probiotics and prebiotics in skin protection against photoaging, we investigated the effects of dietary supplementation with the probiotic, Bifidobacterium longum, and prebiotic, galacto-oligosaccharide, on UVB-induced photoaging in hairless mice. We measured short chain fatty acid (SCFA) levels, antioxidant enzyme activity, and inflammatory signaling protein levels to elucidate the possible mechanisms underlying the effects of the dietary supplements B. longum and galacto-oligosaccharide. We observed that dietary supplementation with B. longum and galacto-oligosaccharide, individually and in combination, exerted protective effects against UVB-induced photoaging, showing anti-inflammatory and antioxidative effects. In particular, supplementation with the combination of B. longum and galacto-oligosaccharide showed stronger protective effects than supplementation with the probiotic or prebiotic alone. In addition, the serum levels of SCFAs and acetate were increased following dietary supplementation with B. longum and galacto-oligosaccharide, especially in combination. Therefore, we suggest that the combination of B. longum and galacto-oligosaccharide may potentially be used as a functional food to protect UVB-induced photoaging.


Assuntos
Bifidobacterium longum , Envelhecimento da Pele , Animais , Bifidobacterium , Camundongos , Camundongos Pelados , Oligossacarídeos/farmacologia , Prebióticos , Raios Ultravioleta/efeitos adversos
4.
J Mater Chem B ; 9(25): 5055-5068, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34132320

RESUMO

Bimodal sub-5 nm superparamagnetic iron oxide nanoparticles (SPIO-5) coated with polyethylene glycol of different chain lengths (i.e. PEG-800, -2000 and -5000) have been prepared and characterized. Fluorescence properties have been obtained by mean of the grafting of a near-infrared-emitting dye (NIR-dye) onto the surface of the oxide, thanks to the carboxylic acid functions introduced towards an organosilane coating. Such modification allowed us to follow in vivo their biodistribution and elimination pathways by T1-w and T2-w high-field magnetic resonance imaging (MRI), as well as by optical and optoacoustic imaging. Interestingly, it has been highlighted that for a given composition, the thickness of the coating strongly influences the pharmacokinetic properties of the administrated SPIO-5.


Assuntos
Nanopartículas Magnéticas de Óxido de Ferro/química , Polietilenoglicóis/química , Animais , Feminino , Camundongos , Camundongos Pelados , Estrutura Molecular , Imagem Óptica , Distribuição Tecidual
5.
Br J Pharmacol ; 178(17): 3414-3427, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33837955

RESUMO

BACKGROUND AND PURPOSE: Protease-activated receptor 1 (PAR1) is a GPCR expressed in several skin cell types, including keratinocyte and dermal fibroblast. PAR1 activation plays a crucial role in the process of skin wound healing such as thrombosis, inflammation, proliferation and tissue repair. In the present study, we identified a novel positive allosteric modulator of PAR1, GB83, and investigated its effect on skin wound healing. EXPERIMENTAL APPROACH: The enhancement of PAR1 activity by GB83 was measured using Fluo-4 calcium assay. In silico docking analysis of GB83 in PAR1 was performed using dock ligands method (CDOCKER) with CHARMm force field. Effects of GB83 on cell viability and gene expression were observed using MTS assay and quantitative real-time PCRs, respectively. SKH-1 hairless mice were used to investigate the wound healing effect of GB83. KEY RESULTS: We demonstrated that GB83 did not activate PAR1 by itself but strongly enhanced PAR1 activation by thrombin and PAR1-activating peptide (AP). In silico docking analysis revealed that GB83 can bind to the PAR1 binding site of vorapaxar. GB83 significantly promoted PAR1-mediated cell viability and migration. In addition, the enhancement of PAR1 activity by GB83 strongly increased gene expression of TGF-ß, fibronectin and type I collagen in vitro and promoted skin wound healing in vivo. CONCLUSION AND IMPLICATIONS: Our results revealed that GB83 is the first positive allosteric modulator of PAR1 and it can be a useful pharmacological tool for studying PAR1 and a potential therapeutic agent for skin wound healing.


Assuntos
Receptor PAR-1 , Cicatrização , Animais , Fibroblastos , Queratinócitos , Camundongos , Camundongos Pelados , Pele
6.
Molecules ; 26(7)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33916154

RESUMO

Plants of the genus Wikstroemia are used in Chinese traditional medicine to treat inflammatory diseases, such as arthritis, bronchitis, and pneumonia. The present study was designed to determine whether Wikstroemia ganpi (Siebold and Zucc.) Maxim. offers a potential means of treating 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) in mice. Symptoms such as redness, edema, and keratinization in AD mice induced by DNCB were alleviated by the co-application of an ethanolic extract of W. ganpi for 2 weeks. The severity of skin barrier function damage was evaluated by measuring TEWL (transepidermal water loss). TEWLs of DNCB sensitized mouse dorsal skin were reduced by the application of a W. ganpi ethanolic extract, and skin hydration was increased. In addition, the infiltration of inflammatory cells into the dermis was significantly reduced, as were blood levels of IgE and IL-4, which play an important role in the expression of AD. The results of this experiment suggest that W. ganpi is a potential therapeutic agent for AD.


Assuntos
Dermatite Atópica/etiologia , Dermatite Atópica/metabolismo , Dinitroclorobenzeno/efeitos adversos , Medicamentos de Ervas Chinesas/farmacologia , Interleucina-4/metabolismo , Extratos Vegetais/farmacologia , Animais , Biópsia , Cromatografia Líquida de Alta Pressão , Citocinas/genética , Citocinas/metabolismo , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/patologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Feminino , Expressão Gênica , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Camundongos , Camundongos Pelados , Estrutura Molecular , Extratos Vegetais/química , Resultado do Tratamento
7.
Int J Biol Macromol ; 181: 221-231, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33774070

RESUMO

Ultraviolet (UV) radiation is known to cause an imbalance of the endogenous antioxidant system leading to an increase in skin cancer. Panax quinquefolium (American ginseng) polysaccharides (GPS) can inhibit such an imbalance due to its anti-oxidative and anti-inflammatory properties. The aim of this study was to investigate the therapeutic effects of topical formulations containing GPS nanoparticles (NPs) to inhibit UVB induced oxidative damage and skin cancer. Photoaging was conducted under UVB irradiation with a dose of 300 mJ/cm2 on SKH1 hairless mice. The treatment groups (n = 5) were as follows: sham control, native GPS, GPS NPs and fluorescent labeled GPS NPs. To compare the photoprotective performance, the topical formulations were applied before and after UVB induction (pre-treatment and post-treatment), followed by sacrificing the animals. Then, skin and blood samples were collected, and inflammatory cytokines production was measured using ELISA. Compared to the sham control, GPS NPs pre-treated mice skin and blood samples exhibited a significant lowering in all cytokine production. In addition, skin histology analysis showed that pre-treatment of GPS NPs prevented epidermal damage and proliferation. The results support that topical formulation containing GPS NPs can inhibit UVB induced oxidative damage and skin cancer.


Assuntos
Nanomedicina , Nanopartículas/administração & dosagem , Nanopartículas/uso terapêutico , Panax/química , Polissacarídeos/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Raios Ultravioleta , Administração Cutânea , Animais , Citocinas/metabolismo , Dano ao DNA , Feminino , Camundongos Pelados , Nanopartículas/ultraestrutura , Tamanho da Partícula , Polissacarídeos/administração & dosagem , Pele/patologia
8.
Food Chem Toxicol ; 151: 112095, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33689855

RESUMO

Skin cancer is a public health problem due to its high incidence. Ultraviolet radiation (UVR) is the main etiological agent of this disease. Photochemoprotection involves the use of substances to avoid damage caused by UV exposure. The aim of this work was to determine the phytochemical fingerprint and photochemoprotective effect against UVB radiation-induced skin damage such as erythema and carcinogenesis of H. mociniana methanolic extract (MEHm). The chemical composition of the MEHm was analysed by LC/ESI-MS/MS. Three quercetin derivatives, two pectinolides, and two caffeic acid derivatives were identified in the methanolic extract. MEHm has antioxidant effect and it is not cytotoxic in HaCaT cells. Phytochemicals from H. mociniana have a photochemopreventive effect because they absorb UV light and protect HaCaT cells from UVR-induced cell death. Also, in SKH-1 mice -acute exposure-, it decreased erythema formation, modulating the inflammatory response, reduced the skin damage according to histological analysis and diminished p53 expression. Finally, MEHm protects from photocarcinogenesis by reducing the incidence and multiplicity of skin carcinomas in SKH-1 mice exposed chronically to UVB radiation.


Assuntos
Eritema/prevenção & controle , Hyptis/química , Neoplasias Induzidas por Radiação/prevenção & controle , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Protetores contra Radiação/farmacologia , Neoplasias Cutâneas/prevenção & controle , Raios Ultravioleta , Animais , Carcinogênese/efeitos dos fármacos , Linhagem Celular , Eritema/etiologia , Feminino , Humanos , Camundongos , Camundongos Pelados , Neoplasias Cutâneas/patologia
9.
Cell Death Dis ; 12(3): 247, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33664254

RESUMO

Cutaneous squamous cell carcinoma (cSCC) is prevalent in the world, accounting for a huge part of non-melanoma skin cancer. Most cSCCs are associated with a distinct pre-cancerous lesion, the actinic keratosis (AK). However, the progression trajectory from normal skin to AK and cSCC has not been fully demonstrated yet. To identify genes involved in this progression trajectory and possible therapeutic targets for cSCC, here we constructed a UV-induced cSCC mouse model covering the progression from normal skin to AK to cSCC, which mimicked the solar UV radiation perfectly using the solar-like ratio of UVA and UVB, firstly. Then, transcriptome analysis and a series of bioinformatics analyses and cell experiments proved that Rorα is a key transcript factor during cSCC progression. Rorα could downregulate the expressions of S100a9 and Sprr2f in cSCC cells, which can inhibit the proliferation and migration in cSCC cells, but not the normal keratinocyte. Finally, further animal experiments confirmed the inhibitory effect of cSCC growth by Rorα in vivo. Our findings showed that Rorα would serve as a potential novel target for cSCC, which will facilitate the treatment of cSCC in the future.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Transformação Celular Neoplásica/metabolismo , Ceratose Actínica/metabolismo , Neoplasias Induzidas por Radiação/metabolismo , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/deficiência , Neoplasias Cutâneas/metabolismo , Animais , Calgranulina B/genética , Calgranulina B/metabolismo , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Proteínas Ricas em Prolina do Estrato Córneo/genética , Proteínas Ricas em Prolina do Estrato Córneo/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Ceratose Actínica/etiologia , Ceratose Actínica/genética , Ceratose Actínica/patologia , Camundongos Pelados , Invasividade Neoplásica , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/genética , Neoplasias Induzidas por Radiação/patologia , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Fatores de Transcrição de Octâmero/genética , Fatores de Transcrição de Octâmero/metabolismo , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Transcriptoma , Raios Ultravioleta
10.
AAPS PharmSciTech ; 22(3): 117, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33768360

RESUMO

This paper aimed to provide an insight into the mechanism of transdermal penetration of drug molecules with respect to their physicochemical properties, such as solubility (S), the presence of enantiomer (ET) and logarithm of octanol-water partition coefficient (log P), molecular weight (MW), and melting point (MP). Propionic acid derivatives were evaluated for their flux through full-thickness skin excised from hairless mice upon being delivered from silicone-based pressure-sensitive adhesive (PSA) matrices in the presence or absence of various enhancers. The skin fluxes of model compounds were calculated based on the data obtained using the method engaged with the diffusion cell system. The statistical design of experiments (DoE) based on the factorial approach was used to find variables that have a significant impact on the outcomes. For the prediction of skin flux, a quantitative equation was derived using the data-mining approach on the relationship between skin permeation of model compounds (~125 mg/ml) and involved physicochemical variables. The most influential variables for the skin flux of propionic acid derivatives were the melting point (0.97) followed by the presence of enantiomer (0.95), molecular mass (0.93), log P values (0.86), and aqueous solubility (0.80). It was concluded that the skin flux of molecular compounds can be predicted based on the relationship between their physicochemical properties and the interaction with cofactors including additives and enhancers in the vehicles.


Assuntos
Mineração de Dados/métodos , Propionatos/administração & dosagem , Propionatos/farmacocinética , Absorção Cutânea/efeitos dos fármacos , Absorção Cutânea/fisiologia , Administração Cutânea , Animais , Fenômenos Químicos , Camundongos , Camundongos Pelados , Técnicas de Cultura de Órgãos/métodos , Propionatos/química , Pele/efeitos dos fármacos , Pele/metabolismo , Solubilidade
11.
BMC Complement Med Ther ; 21(1): 82, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658026

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a chronic allergic inflammatory skin disease characterized by complex pathogenesis including skin barrier dysfunction, immune-redox disturbances, and pruritus. Prolonged topical treatment with medications such as corticosteroids, calcineurin inhibitors, and T-cell inhibitors may have some potential side-effects. To this end, many researchers have explored numerous alternative therapies using natural products and mineral compounds with antioxidant or immunomodulatory effects to minimize toxicity and adverse-effects. In the current study, we investigated the effects of mineral complex material (MCM) treatment on 2, 4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in SKH-1 hairless mice. METHODS: Animals were divided into four groups; normal control (NC), negative control treated with DNCB only (DNCB only), positive control treated with DNCB and tacrolimus ointment (PC) and experimental group treated with DNCB and MCM patch (MCM). Skin inflammation and lesion severity were investigated through analyses of skin parameters (barrier score and strength, moisture and trans-epidermal water loss level), histopathology, immunoglobulin E, and cytokines. In addition, reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), and catalase (CAT) levels were measured in both serum and skin lysate. RESULTS: Our results demonstrates that MCM patch improved the progression of AD-like skin lesions by significantly increasing skin barrier strength and decreasing trans-epidermal water loss. Additionally, dermal administration of MCM patch significantly reduced epidermal thickness, ROS, and NO levels in skin lysate. Furthermore, we found that MCM suppressed the levels of AD-involved (Th1 and Th2) cytokines such as IL-2, IFN-γ, and IL-4 in blood. In addition, the levels of other Th1, and Th2 and inflammatory cytokines such as IL-1ß, TNF-α, IL-6, IL-12(p70) and IL-10 were found lowest in the MCM group than in the DNCB only and PC groups. Moreover, we found total serum IgE level significantly increased after DNCB treatment, but decreased in the PC and MCM groups. CONCLUSION: Taken together, our findings suggest that MCM application may have beneficial effects either systemic or regional on DNCB-induced AD lesional skin via regulation of the skin barrier function and immune-redox response.


Assuntos
Dermatite Atópica/tratamento farmacológico , Minerais/administração & dosagem , Animais , Citocinas/metabolismo , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Dinitroclorobenzeno/efeitos adversos , Modelos Animais de Doenças , Feminino , Humanos , Imunoglobulina E/metabolismo , Camundongos , Camundongos Pelados , Óxido Nítrico/metabolismo , Pele/efeitos dos fármacos , Pele/patologia
12.
J Photochem Photobiol B ; 216: 112151, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33581679

RESUMO

Photochemoprotection of the skin can be achieved by inhibiting inflammation and oxidative stress, which we tested using Cordia verbenacea extract, a medicinal plant known for its rich content of antioxidant molecules and anti-inflammatory activity. In vitro antioxidant evaluation of Cordia verbenacea leaves ethanolic extract (CVE) presented the following results: ferric reducing antioxidant power (886.32 µM equivalent of Trolox/g extract); IC50 of 19.128 µg/ml for scavenging 2,2-diphenyl-1-picrylhydrazyl; IC50 of 12.48 µg/mL for scavenging 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid); decrease of hydroperoxides from linoleic acid (IC50 of 10.20 µg/mL); inhibition of thiobarbituric acid reactive substances (IC50 8.90 µg/mL); iron-chelating ability in bathophenanthroline iron assay (IC50 47.35 µg/mL); chemiluminescence triggered by free radicals in the H2O2/horseradish peroxidase/luminol (IC50 0.286 µg/mL) and xanthine/xanthine oxidase/luminol (IC50 0.42 µg/mL) methods. CVE (10-100 mg per kg, 30 min before and immediately after UVB exposure) treatment was performed by gavage in hairless mice. CVE inhibited skin edema, neutrophil infiltration, and overproduction of MMP-9; reduced levels of TNF-α, IL-1ß, and IL- 6; numbers of skin mast cells, epidermal thickening, number of epidermal apoptotic keratinocytes, and collagen degradation. CVE increased the skin's natural antioxidant defenses as observed by Nrf-2, NAD(P)H quinone oxidoreductase 1, and heme oxygenase 1 mRNA expression enhancement. Furthermore, CVE inhibited lipid peroxidation and superoxide anion production and recovered antioxidant reduced glutathione, catalase activity, and ROS scavenging capacity of the skin. Concluding, CVE downregulates the skin inflammatory and oxidative damages triggered by UVB, demonstrating its potentialities as a therapeutic approach.


Assuntos
Anti-Inflamatórios/química , Antioxidantes/química , Cordia/química , Extratos Vegetais/química , Folhas de Planta/química , Substâncias Protetoras/química , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Citocinas/metabolismo , Edema/metabolismo , Feminino , Heme Oxigenase-1/metabolismo , Humanos , Peróxido de Hidrogênio/química , Ácido Linoleico/química , Peroxidação de Lipídeos , Camundongos Pelados , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Quinona Redutases/metabolismo , Pele/efeitos da radiação , Superóxidos/metabolismo , Raios Ultravioleta
13.
Amino Acids ; 53(3): 429-434, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33608821

RESUMO

Taurine, a sulfur-containing amino acid, occurs at high concentrations in the skin, and plays a role in maintaining the homeostasis of the skin. We investigated the effects of aging on the content and localization of taurine in the skin of mice and rats. Taurine was extracted from the skin samples of hairless mice and Sprague Dawley rats, and the taurine content of the skin was determined by high-performance liquid chromatography (HPLC). The results of the investigation revealed that the taurine content in both the dermis and epidermis of hairless mice declined significantly with age. Similar age-related decline in the skin taurine content was also observed in rats. In contrast, the taurine content in the sole remained unchanged with age. An immunohistochemical analysis also revealed a decreased skin taurine content in aged animals compared with younger animals, although no significant differences in the localization of taurine were observed between the two age groups. Supplementation of the drinking water of aged mice with 3% (w/v) taurine for 4 weeks increased the taurine content of the epidermis, but not the dermis. The present study showed for the first time that the taurine content of the skin decreased with age in mice and rats, which may be related to the impairment of the skin homeostasis observed with aging. The decreased taurine content of the epidermis in aged animals was able to be rescued by taurine supplementation.


Assuntos
Envelhecimento/patologia , Pele/química , Taurina/análise , Envelhecimento/efeitos dos fármacos , Animais , Suplementos Nutricionais , Epiderme/química , Homeostase/efeitos dos fármacos , Masculino , Camundongos , Camundongos Pelados , Ratos , Ratos Sprague-Dawley , Taurina/administração & dosagem , Taurina/farmacologia
14.
Anal Bioanal Chem ; 413(10): 2793-2801, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33388847

RESUMO

Three-dimensional (3D) mass spectrometry imaging (MSI) has become a growing frontier as it has the potential to provide a 3D representation of analytes in a label-free, untargeted, and chemically specific manner. The most common 3D MSI is accomplished by the reconstruction of 2D MSI from serial cryosections; however, this presents significant challenges in image alignment and registration. An alternative method would be to sequentially image a sample by consecutive ablation events to create a 3D image. In this study, we describe the use of infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) in ablation-based 3D MSI for analyses of lipids within fresh frozen skin tissue. Depth resolution using different laser energy levels was explored with a confocal laser scanning microscope to establish the imaging parameters for skin. The lowest and highest laser energy level resulted in a depth resolution of 7 µm and 18 µm, respectively. A total of 594 lipids were putatively detected and detailed lipid profiles across different skin layers were revealed in a 56-layer 3D imaging experiment. Correlated with histological information, the skin structure was characterized with differential lipid distributions with a lateral resolution of 50 µm and a z resolution of 7 µm.


Assuntos
Imageamento Tridimensional/métodos , Lipídeos/análise , Pele/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Animais , Camundongos , Camundongos Pelados , Espectrometria de Massas por Ionização por Electrospray/métodos
15.
J Cosmet Dermatol ; 20(9): 2743-2749, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33421303

RESUMO

BACKGROUND: Polydioxanone (PDO) threads, poly-L-lactic acid (PLLA) threads, and polycaprolactone (PCL) threads have been used for lifting and antiaging purposes. The new PCL threads that have less residual monomer compared to the previous PCL are developed. AIMS: The efficacy of threads regarding collagen synthesis and wrinkle improvement was evaluated in vivo model. METHODS: In this study, threads were inserted into 30 six-week-old male SKH-1 hairless mice. One of four threads was implanted at either side of the spine of each mouse. Biopsy specimens obtained at 1, 4, and 8 weeks were examined using hematoxylin and eosin (H&E) and Herovici's stain. Additionally, immunoblot analysis was performed using primary antibody for collagen type III and transforming growth factor-ß (TGF-ß) and visualized by chemiluminescence and densitometric quantification. Finally, skin replicas were used to calculate total wrinkle area (mm2 ). RESULTS: Neocollagenesis was significantly increased by 50% in the new PCL and pre-existing PCL groups at 8 weeks (p value < 0.001). Additionally, new-PCL-implanted mice showed a significant increase in collagen type III and TGF-ß expressions at 8 weeks (p value < 0.001). The number of inflammatory cells was also increased in the skin of PCL-implanted mice at 8 weeks. Finally, wrinkles were reduced about 20% in the new PCL group at 8 weeks. CONCLUSIONS: The new PCL thread exhibited a superior skin rejuvenation effect. This suggests that the material processing technology can be applied not only to the thread but also to various products such as dermal filler and cosmetics.


Assuntos
Polidioxanona , Rejuvenescimento , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Pelados , Poliésteres
16.
Lasers Med Sci ; 36(4): 863-870, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32827076

RESUMO

Ultraviolet radiation (UVR) is the major etiologic agent of cutaneous photoaging, and different strategies are used to prevent and treat this condition. The polysaccharide fraction (LBPF) isolated from Lycium Barbarum fruits (goji berry) contains several active ingredients with antioxidant, immune system modulation, and antitumor effects. In addition, the photobiomodulation (PBM) is widely applied in photoaging treatment. This study investigated the effects of LBPF and PBM against the UVR-induced photodamage in the skin of hairless mice. The mice were photoaged for 6 weeks in a chronic and cumulative exposure regimen using a 300-W incandescent lamp that simulates the UVR effects. From the third to the sixth week of photoaging induction, the animals received topical applications of LBPF and PBM, singly or combined, in different orders (first LBPF and then PBM and inversely), three times per week after each session of photoaging. After completion of experiments, the dorsal region skin was collected for the analysis of thickness, collagen content, and metalloproteinases (MMP) levels. A photoprotective potential against the increase of the epithelium thickness and the fragmentation of the collagen fibers was achieved in the skin of mice treated with LBPF or PBM singly, as well as their combination. All treatments maintained the skin collagen composition, except when PBM was applied after the LBPF. However, no treatment protected against the UVR-induced MMP increase. Taken together, we have shown that the LBPF and PBM promote a photoprotective effect in hairless mice skin against epidermal thickening and low collagen density. Both strategies, singly and combined, can be used to reduce the UVR-induced cutaneous photoaging.


Assuntos
Colágeno/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Epitélio/efeitos dos fármacos , Epitélio/efeitos da radiação , Terapia com Luz de Baixa Intensidade , Pele/patologia , Pele/efeitos da radiação , Animais , Epitélio/patologia , Camundongos , Camundongos Pelados , Pele/efeitos dos fármacos , Pele/metabolismo , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/patologia , Envelhecimento da Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos
17.
Pharm Dev Technol ; 26(2): 209-219, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33258705

RESUMO

PURPOSE: The objective of this study was to develop silibinin-loaded hydrogel for skin protection against UVB damage. METHOD: Physical grafting was used to prepare hydrogel based on chitosan-fucoidan. Then, hydrogel properties, such as swelling, drug release rates, morphology, and structure, were evaluated to determine the optimum hydrogel for in vivo studies. In in vivo experiments, the silibinin permeability parameters were investigated through normal and UV-irradiated skin, anti-inflammatory property, and antioxidant effects after application of optimum hydrogel. RESULTS: The silibinin completely dispersed in the hydrogel, and FT-IR results showed that silibinin reacted with the chitosan and fucoidan and demonstrated a slow release pattern. The 50% and less than 70% of the drug-loaded on hydrogel were passed through normal and irradiated skin after 48 h, respectively. In vivo studies showed the effectiveness of optimized hydrogel in preventing the production of oxidative species and H2O2 after UVB radiation. Histological studies have shown that silibinin-loaded optimized hydrogel can prevent the hyperkeratosis, acanthosis, and infiltration of neutrophils into the dermis by UVB. CONCLUSION: Optimized hydrogel effectively reduced the inflammation mediators interleukin-22 and TNF-α, which signify tissue destruction. Therefore, silibinin-loaded hydrogel can be introduced as an effective sun-protective product.


Assuntos
Quitosana/química , Polissacarídeos/química , Silibina/administração & dosagem , Raios Ultravioleta/efeitos adversos , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Preparações de Ação Retardada , Feminino , Hidrogéis , Peróxido de Hidrogênio/metabolismo , Inflamação/prevenção & controle , Camundongos , Camundongos Pelados , Silibina/farmacologia , Pele/efeitos dos fármacos , Pele/efeitos da radiação
18.
J Nat Med ; 75(1): 142-155, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33201413

RESUMO

This study was conducted to investigate whether and how Jumihaidokuto (JHT), a traditional Chinese medicine, prevents UVB-induced skin damage in male HR-1 hairless mice. JHT has been traditionally prescribed for patients presenting skin disorders with redness and swelling, and, in Japan, it is approved for prescription to patients with acute and/or purulent skin disorders, hives, acute eczema, and athlete's foot. Considering the traditional use of JHT, we hypothesized that oral administration of JHT might emerge as an effective strategy to prevent UVB-induced skin damage, such as edema and erythema. Here, we pretreated mice with JHT (1000 mg/kg, p.o.) for 3 weeks and then administered a single dose of UVB irradiation (250 mJ/cm2) on the dorsal skin. UVB irradiation increased the erythema index and transepidermal water loss (TEWL) and decreased the skin water content in the epidermis at 72 h post-irradiation. JHT treatment inhibited the increase of TEWL and the loss of water content in the epidermis, but not the elevation of the erythema index. Moreover, administration of JHT suppressed UVB-induced epidermal hyperplasia by blocking the proliferation of keratinocytes and also inhibited irradiation-triggered reduction of collagen fibers and infiltration of immune cells into the dermis. Lastly, administration of JHT suppressed UVB-induced production of proinflammatory mediators, such as prostaglandin E2 and interleukin-1ß. These results suggest that JHT prevents UVB-induced skin damage and that the underlying mechanism involves the inhibition of proinflammatory mediators.


Assuntos
Dinoprostona/metabolismo , Medicina Tradicional Chinesa/métodos , Extratos Vegetais/uso terapêutico , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos , Administração Oral , Animais , Humanos , Masculino , Camundongos , Camundongos Pelados , Extratos Vegetais/farmacologia
19.
J Cosmet Dermatol ; 20(9): 2932-2939, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33356000

RESUMO

BACKGROUND: Ultraviolet B (UVB) irradiation is viewed as the main factor of skin aging, associated with acceleration of elastin, collagen degradation and expression of matrix metalloproteinases (MMPs). Apples are one of the most commonly eaten fruits in the world, and isoquercitrin is the main active ingredient in new bred varieties "Green ball" apple. Therefore, we are studying the functionality of the active ingredient of apple, a natural raw material that does not have toxicity or sensitivity problems. OBJECTIVES: The aim of this study, we scrutinized the effects of isoquercitrin on skin photoaging in UVB-exposed human fibroblasts (CCD-986Sk). METHODS: To investigate the inhibition effect on photoaging factor regulation, isolated isoquercitrin were treated with UVB, which induces photoaging-related factors in CCD-986Sk fibroblast cells. Pro-inflammatory factors were measured by ELISA, Western blotting and real-time PCR. RESULTS: Isoquercitrin exhibited antioxidant activity and UVB-induced generation of photoaging-related factor inhibition without showing any toxicity. Anti-photoaging effect for protein levels using Isoquercitin was competent, of both the combate MMP-1 and MMP-9. Also, effect of COL1A2 product significantly increase, from up regulating the TIMP-1 mediated pathway in CCD-986Sk cells via the inhibition of MMPs. Isoquercitrin also downregulated the mRNA gene expression of MMPs while upregulating type I procollagen, HAS2 by modulating TIMP-1 and TGF-ß in UVB-irradiated CCD-986Sk cells. CONCLUSIONS: Collectively, our results show that isoquercitrin might be useful as a functional food while being a good candidate in the development of cosmetic products and medicines for the remedy of UVB-induced skin photoaging.


Assuntos
Malus , Envelhecimento da Pele , Animais , Fibroblastos , Humanos , Metaloproteinases da Matriz , Camundongos , Camundongos Pelados , Quercetina/análogos & derivados , Pele , Raios Ultravioleta/efeitos adversos
20.
Methods Mol Biol ; 2223: 79-86, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33226588

RESUMO

Atopic dermatitis (AD) is a common skin disease characterized by chronic inflammation and itchiness. Although skin barrier dysfunction and immune abnormalities are thought to contribute to the development of AD, the precise pathogenic mechanism remains to be elucidated. We have developed a unique, diet-induced AD mouse model based on the findings that deficiencies of certain polyunsaturated fatty acids and starches cause AD-like symptoms in hairless mice. Here, we present a protocol and tips for establishing an AD mouse model using a custom diet modified from a widely used standard diet (AIN-76A Rodent Diet). We also describe methods for evaluating skin barrier dysfunction and analyzing itch-related scratching behavior. This model can be used not only to investigate the complex pathogenic mechanism of human AD but also to study the puzzling relationship between nutrition and AD development.


Assuntos
Dermatite Atópica/imunologia , Modelos Animais de Doenças , Ácidos Graxos Insaturados/química , Alimentos Formulados , Prurido/imunologia , Amido/química , Animais , Comportamento Animal , Óleo de Milho/química , Dermatite Atópica/etiologia , Dermatite Atópica/fisiopatologia , Etanol/química , Ácidos Graxos Insaturados/deficiência , Ácidos Graxos Insaturados/imunologia , Feminino , Humanos , Camundongos , Camundongos Pelados , Permeabilidade , Prurido/etiologia , Prurido/fisiopatologia , Pele/efeitos dos fármacos , Pele/imunologia , Pele/patologia , Amido/deficiência , Amido/imunologia
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