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1.
Medicine (Baltimore) ; 99(6): e19051, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32028422

RESUMO

Adult-onset Still disease (AOSD), a systemic inflammatory disorder, is characterized by high fever, evanescent rash, arthritis, and hyperferritinaemia. AOSD is also reported to be associated with other skin lesions, including persistent pruritic papules and plaques. This study aimed to assess the significance of dyskeratotic skin lesions in Japanese AOSD patients.We retrospectively assessed the histology of persistent pruritic skin lesions and evanescent rashes and the relationship between dyskeratotic cells, serum markers, and outcomes in 20 Japanese AOSD patients, comparing AOSD histology with that of dermatomyositis (DM), drug eruptions, and graft-versus-host disease (GVHD).As the results, Persistent pruritic lesions were characterized by scattered single keratinocytes with an apoptotic appearance confined to the upper layer of the epidermis and horny layer without inflammatory infiltrate. In contrast to AOSD, the histology of DM, drug eruption, and GVHD demonstrated dyskeratotic cells in all layers of the epidermis with inflammatory infiltrate. AOSD with evanescent rash showed no dyskeratotic cells. The dyskeratotic cells in pruritic AOSD lesions stained positive for ssDNA and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, indicating apoptosis. Serum IL-18 was significantly higher in AOSD patients with dyskeratotic cells than those without, and generally required higher doses of glucocorticoids, immunosuppressants, and biologic agents. Two of ten AOSD patients with dyskeratotic cells died from hemophagocytic lymphohistiocytosis.In conclusion, Persistent pruritic AOSD skin lesions are characterized by dyskeratotic cells with apoptotic features, involving the upper layers of the epidermis. There may be a link to elevated IL-18. This dyskeratosis may be a negative prognostic indicator.


Assuntos
Queratinócitos/patologia , Prurido/patologia , Pele/patologia , Doença de Still de Início Tardio/diagnóstico , Apoptose , Feminino , Humanos , Interleucina-18/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Prurido/diagnóstico , Estudos Retrospectivos , Pele/citologia , Doença de Still de Início Tardio/patologia
3.
Nat Commun ; 10(1): 4790, 2019 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-31636353

RESUMO

Alterations of Ca2+ homeostasis have been implicated in a wide range of neurodegenerative diseases. Ca2+ efflux from the endoplasmic reticulum into the cytoplasm is controlled by binding of inositol 1,4,5-trisphosphate to its receptor. Activated inositol 1,4,5-trisphosphate receptors are then rapidly degraded by the endoplasmic reticulum-associated degradation pathway. Mutations in genes encoding the neuronal isoform of the inositol 1,4,5-trisphosphate receptor (ITPR1) and genes involved in inositol 1,4,5-trisphosphate receptor degradation (ERLIN1, ERLIN2) are known to cause hereditary spastic paraplegia (HSP) and cerebellar ataxia. We provide evidence that mutations in the ubiquitin E3 ligase gene RNF170, which targets inositol 1,4,5-trisphosphate receptors for degradation, are the likely cause of autosomal recessive HSP in four unrelated families and functionally evaluate the consequences of mutations in patient fibroblasts, mutant SH-SY5Y cells and by gene knockdown in zebrafish. Our findings highlight inositol 1,4,5-trisphosphate signaling as a candidate key pathway for hereditary spastic paraplegias and cerebellar ataxias and thus prioritize this pathway for therapeutic interventions.


Assuntos
Degradação Associada com o Retículo Endoplasmático/genética , Fibroblastos/metabolismo , Neurônios/metabolismo , Paraplegia Espástica Hereditária/genética , Ubiquitina-Proteína Ligases/genética , Adolescente , Adulto , Animais , Cálcio/metabolismo , Linhagem Celular Tumoral , Criança , Pré-Escolar , Retículo Endoplasmático/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Inositol 1,4,5-Trifosfato/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Masculino , Pessoa de Meia-Idade , Cultura Primária de Células , Transdução de Sinais , Pele/citologia , Paraplegia Espástica Hereditária/metabolismo , Peixe-Zebra
4.
J Biochem Mol Toxicol ; 33(11): e22402, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31576639

RESUMO

INTRODUCTION: Galbanic acid (GA) is a natural bioactive compound abundantly distributed in Ferula species (Apiaceae), with a wide range of biological functions. METHODS: The present study investigated the anticancer properties of GA in human breast carcinoma MCF-7 and MDA-MB-231 cell lines using MTT (3,4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide) assay. Further, the antioxidant activity of GA was determined in vitro. The plausible mechanisms of action of GA were further investigated using flow cytometry and gene expression analysis. RESULTS: Our study indicated that treatment with GA resulted in inhibition of proliferation and induction of apoptosis in MDA-MB-231 cells. The obtained results indicated that GA has strong cytotoxicity on MDA-MB-231 cells (IC50 = 48.75 µg/mL) compare to MCF-7 (IC50 = 56.65 µg/mL) and decrease cancer cell viability in the dose- and time-dependent manner. Meanwhile, microscopic examination and flow cytometry analysis confirmed the apoptosis cell death upon treatment with GA. The gene expression analysis revealed that GA could induce apoptosis-mediated proliferation inhibition in MDA-MB-231 cells through upregulation of bax and caspase-3 and downregulation of bcl2 genes. Besides, the GA exhibited free radical-scavenging activity and enhanced the cellular redox state in human dermal fibroblasts. The elevation of cellular redox status was confirmed by upregulating superoxide dismutase, catalase, and glutathione peroxidase genes. CONCLUSION: The results obtained in this study indicated that GA could be considered as a promising anticancer agent in breast cancer therapy and a bioactive antioxidant compound to be used in pharmaceutical and cosmetic industries.


Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Neoplasias da Mama/metabolismo , Proliferação de Células/efeitos dos fármacos , Cumarínicos/farmacologia , Extratos Vegetais/farmacologia , Receptores Estrogênicos/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Caspase 3/genética , Catalase/genética , Sobrevivência Celular/efeitos dos fármacos , Feminino , Ferula/química , Fibroblastos/metabolismo , Radicais Livres , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glutationa Peroxidase/genética , Humanos , Células MCF-7 , Oxirredução , Proteínas Proto-Oncogênicas c-bcl-2/genética , Pele/citologia , Superóxido Dismutase/genética , Proteína X Associada a bcl-2/genética
5.
Int J Nanomedicine ; 14: 7003-7016, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564862

RESUMO

Background: Yttria-stabilized zirconia (Y2O3/ZrO2) nanoparticles are one of the important nanoparticles extensively used in manufacturing of plastics, textiles, catalyst, etc. Still, the cytotoxic and apoptotic effects of yttria-stabilized zirconia nanoparticles have not been well identified on human skin keratinocyte (HaCaT) cells. Therefore, in this study, we have designed to examine the cytotoxic potential of yttria-stabilized zirconia nanoparticles in HaCaT cells. Methods: Prior to treatment, the yttria-stabilized zirconia nanoparticles were characterized by using different advanced instruments viz. dynamic light scattering (DLS), scanning electron microscope (SEM) and transmission electron microscope (TEM). Cell viability of HaCaT cells was measured by using MTS and NRU assays and viability of cells was reduced in a dose- and time-dependent manner. Results: Reduction in the viability of cells was correlated with the rise of reactive oxygen species generation, increased caspase-3, mitochondria membrane potential and evidence of DNA strand breakage. These were consistent with the possibility that mitochondria damage can play a significant role in the cytotoxic response. Moreover, the activity of oxidative enzymes such as lipid peroxide (LPO) was increased and glutathione was reduced in HaCaT cells exposed with yttria-stabilized zirconia nanoparticles. It is also important to indicate that HaCaT cells appear to be more susceptible to yttria-stabilized zirconia nanoparticles exposure after 24 hrs. Conclusion: This result provides a dose- and time-dependent apoptosis and genotoxicity of yttria-stabilized zirconia nanoparticles in HaCaT cells.


Assuntos
Apoptose , Dano ao DNA , Células Epiteliais/citologia , Nanopartículas Metálicas/química , Pele/citologia , Ítrio/química , Zircônio/química , Acetilcisteína/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Células Epiteliais/metabolismo , Glutationa/metabolismo , Humanos , Membranas Intracelulares/efeitos dos fármacos , Membranas Intracelulares/metabolismo , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Nanopartículas Metálicas/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
6.
Forensic Sci Int Genet ; 43: 102153, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31505370

RESUMO

Data from all sexual assault cases analysed at the Section of Forensic Biology at Oslo University Hospital in the period 2013-2015 were reviewed to study transfer and persistence of cells deposited on the body. Data were recorded on detection of both sperm and epithelial cells. The final dataset consist of 2141 samples from 765 cases. In this study "positive findings" refer to evidence to support the proposition that the DNA profile was contributed by the POI and do not only correspond to detection of cell type, e.g. sperm cells. Positive findings from analysis of sperm cells could be detected in samples collected up to 72 h after deposition, and was less frequently detected in oral swabs were the longest observed persistence time was 12 h. Positive findings from analysis of epithelial cells were observed up to 43 h after deposition. A high success rate was observed from penile swabs collected within 24 h of the incidence demonstrating the importance of collecting and analysing such samples in cases where no semen is detected.


Assuntos
Impressões Digitais de DNA , DNA/isolamento & purificação , Células Epiteliais/citologia , Delitos Sexuais , Espermatozoides/citologia , Células Epiteliais/química , Feminino , Genética Forense/métodos , Humanos , Masculino , Boca/citologia , Reação em Cadeia da Polimerase , Reto/citologia , Estudos Retrospectivos , Pele/citologia , Manejo de Espécimes , Espermatozoides/química , Fatores de Tempo , Vagina/citologia , Vulva/citologia
7.
Nat Commun ; 10(1): 4401, 2019 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-31562311

RESUMO

Tissue-resident memory CD8+ T (Trm) cells mediate potent local innate and adaptive immune responses and play a central role against solid tumors. However, whether Trm cells cross-talk with dendritic cells (DCs) to support anti-tumor immunity remains unclear. Here we show that antigen-specific activation of skin Trm cells leads to maturation and migration to draining lymph nodes of cross-presenting dermal DCs. Tumor rejection mediated by Trm cells triggers the spread of cytotoxic CD8+ T cell responses against tumor-derived neo- and self-antigens via dermal DCs. These responses suppress the growth of intradermal tumors and disseminated melanoma lacking the Trm cell-targeted epitope. Moreover, analysis of RNA sequencing data from human melanoma tumors reveals that enrichment of a Trm cell gene signature associates with DC activation and improved survival. This work unveils the ability of Trm cells to amplify the breath of cytotoxic CD8+ T cell responses through DCs, thereby strengthening anti-tumor immunity.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Memória Imunológica/imunologia , Melanoma/imunologia , Pele/imunologia , Animais , Antígenos/imunologia , Movimento Celular/imunologia , Apresentação Cruzada/imunologia , Humanos , Linfonodos/imunologia , Melanoma/patologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pele/citologia , Linfócitos T Citotóxicos/imunologia
8.
Chem Commun (Camb) ; 55(80): 12036-12039, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31531454

RESUMO

While commercially available suncare products are effective at absorbing ultraviolet (UV)-light, recent studies indicate systemic toxicities associated with many traditional chemical and physical UV-filters. We demonstrate the application of xanthommatin, a biochrome present in arthropods and cephalopods, as an alternative chemical UV-filter that is cytocompatible while maintaining its photostability and photoprotective properties.


Assuntos
Antioxidantes/farmacologia , Oxazinas/farmacologia , Pele/efeitos da radiação , Protetores Solares/farmacologia , Xantenos/farmacologia , Animais , Antioxidantes/química , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Dimetilpolisiloxanos/química , Humanos , Camundongos , Células NIH 3T3 , Oxazinas/química , Estudo de Prova de Conceito , Pele/citologia , Protetores Solares/química , Raios Ultravioleta , Xantenos/química
9.
Adv Exp Med Biol ; 1169: 55-62, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31487018

RESUMO

Sweat glands play an important role in skin physiology and are an integral part of the natural skin barrier. In order to maintain functionality throughout life, sweat glands make use of several types of stem cells. This chapter focuses on the classification of different types of stem cells found in the sweat gland and their physiological roles. First, sweat gland formation during skin maturation is addressed in order to give an overview of sweat gland origin and formation in vivo. Then, different kinds of adult sweat gland stem cells are introduced and classified between different potency levels and corresponding physiological roles. Finally, the importance of these cell sources for future developments, including applications in wound healing and cosmetics research, is discussed.


Assuntos
Células-Tronco , Glândulas Sudoríparas , Humanos , Pele/citologia , Pele/crescimento & desenvolvimento , Células-Tronco/citologia , Glândulas Sudoríparas/citologia , Cicatrização
10.
Nat Commun ; 10(1): 4019, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488820

RESUMO

Biological cellular structures have inspired many scientific disciplines to design synthetic structures that can mimic their functions. Here, we closely emulate biological cellular structures in a rationally designed synthetic multicellular hybrid ion pump, composed of hydrogen-bonded [EMIM+][TFSI-] ion pairs on the surface of silica microstructures (artificial mechanoreceptor cells) embedded into thermoplastic polyurethane elastomeric matrix (artificial extracellular matrix), to fabricate ionic mechanoreceptor skins. Ionic mechanoreceptors engage in hydrogen bond-triggered reversible pumping of ions under external stimulus. Our ionic mechanoreceptor skin is ultrasensitive (48.1-5.77 kPa-1) over a wide spectrum of pressures (0-135 kPa) at an ultra-low voltage (1 mV) and demonstrates the ability to surpass pressure-sensing capabilities of various natural skin mechanoreceptors (i.e., Merkel cells, Meissner's corpuscles, Pacinian corpuscles). We demonstrate a wearable drone microcontroller by integrating our ionic skin sensor array and flexible printed circuit board, which can control directions and speed simultaneously and selectively in aerial drone flight.


Assuntos
Técnicas Biossensoriais/instrumentação , Eletroquímica/instrumentação , Ligações de Hidrogênio , Mecanorreceptores/fisiologia , Mecanotransdução Celular/fisiologia , Fenômenos Fisiológicos da Pele , Adulto , Biomimética/instrumentação , Técnicas Biossensoriais/métodos , Humanos , Mecanorreceptores/química , Mecanorreceptores/citologia , Células de Merkel/metabolismo , Estimulação Física , Poliuretanos , Pressão , Sílica Gel , Pele/citologia , Tato/fisiologia
11.
Biol Pharm Bull ; 42(9): 1510-1516, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474711

RESUMO

The ability of dermal fibroblasts to synthesize collagen decreases with ages. The integrity of collagen fibers severely decreases in aged skin, causing its characteristic morphological changes such as wrinkles and sagging. To prevent and improve skin aging, the stimulation of collagen synthesis in dermal fibroblasts is important. Potato peels contain many biofunctional compounds, but not much is known about their effects on human skin physiology. To characterize the potential effects of a potato peel extract (PPE) against skin aging, we examined its effects on the synthesis of type I collagen by normal human dermal fibroblasts (NHDFs). Treatment with the PPE significantly increased the expression of type I collagen mRNA in NHDFs and their secretion of type I collagen. To elucidate the mechanism involved, we examined the signaling pathway controlled by transforming growth factor-ß (TGF-ß), which regulates the synthesis of type I collagen. Treatment of NHDFs with the PPE significantly increased the expression of TGF-ß receptor mRNA. TGF-ß signaling involves Smad-dependent and Smad-independent pathways, like phosphatidylinositol-3 kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK). The PPE did not activate Smad, but significantly activated Akt and ERK. These results demonstrate that the PPE activates PI3K/Akt and MAPK/ERK signals via TGF-ß receptors, which stimulate the synthesis of type I collagen in NHDFs. These results suggest that the PPE could be a novel and effective antiaging material.


Assuntos
Colágeno Tipo I/biossíntese , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fibroblastos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pele/citologia , Solanum tuberosum/química , Técnicas de Cultura de Células , Células Cultivadas , Fibroblastos/metabolismo , Humanos , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Transdução de Sinais , Pele/metabolismo , Envelhecimento da Pele/efeitos dos fármacos
12.
Bioelectromagnetics ; 40(7): 445-457, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31429952

RESUMO

This paper proposes a novel in vitro exposure system operating at millimeter-wave (mmWave) 28 GHz, one of the frequency bands under consideration for fifth generation (5G) communication. We employed the field uniformity concept along cross-sectional observation planes at shorter distances from the radiation antenna for better efficiency and a small-size system. A choke-ring antenna was designed for this purpose in consideration of a wider beamwidth (BW) and a symmetric far-field pattern across three principal planes. The permittivity of Dulbecco's modified Eagle's medium solution was measured to examine the specific absorption rate (SAR) of the skin cell layer inside a Petri dish model for a three-dimensional (3D) cell culture in vitro experiment. The best deployment of Petri dishes, taking into account a geometrical field symmetry, was proposed. Local SAR values within the cell layer among the Petri dishes were determined with different polarization angles. It was determined that this polarization effect should be considered when the actual exposure and deployment were conducted. We finally proposed an in vitro exposure system based on the field uniformity including downward exposure from an antenna for 3D cell culture experiments. A small-size chamber system was obtained, and the size was estimated using the planar near-field chamber design rule. Bioelectromagnetics. 2019;40:445-457. © 2019 Bioelectromagnetics Society.


Assuntos
Simulação por Computador , Campos Eletromagnéticos/efeitos adversos , Radiação Eletromagnética , Modelos Biológicos , Células Cultivadas , Meios de Cultura , Humanos , Doses de Radiação , Pele/citologia , Pele/metabolismo
13.
Opt Lett ; 44(17): 4119-4122, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31465343

RESUMO

Detailed assessment of skin conditions or the efficacy of skin treatments could greatly benefit from noninvasively assessing the distribution of cutaneous and subcutaneous structures and biomolecules. We considered ultrawideband raster scan optoacoustic mesoscopy with an extended wavelength range from visible to short-wave infrared and observed previously unseen high-resolution images of lipids colocalized with water, melanin, and hemoglobin distribution in human skin. Based on this contrast, the technique resolves subcutaneous fat, the pilosebaceous unit with complete hair strand and bulb, dermal microvasculature, and epidermal structures. We further visualize melanoidins that form via the Maillard reaction in the ultrathin stratum corneum layer, analyze their absorption spectrum, and separate them from the melanin layer. The suggested method may allow novel interrogation of skin conditions, possibly impacting diagnostics and medical and cosmetic treatments.


Assuntos
Raios Infravermelhos , Fenômenos Ópticos , Técnicas Fotoacústicas , Pele/diagnóstico por imagem , Tecido Adiposo/citologia , Hemoglobinas/metabolismo , Humanos , Metabolismo dos Lipídeos , Melaninas/metabolismo , Pele/citologia , Pele/metabolismo , Água/metabolismo
14.
Nat Commun ; 10(1): 3831, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444339

RESUMO

When injured, fish release an alarm substance (Schreckstoff) that elicits fear in members of their shoal. Although Schreckstoff has been proposed to be produced by club cells in the skin, several observations indicate that these giant cells function primarily in immunity. Previous data indicate that the alarm substance can be isolated from mucus. Here we show that mucus, as well as bacteria, are transported from the external surface into club cells, by cytoplasmic transfer or invasion of cells, including neutrophils. The presence of bacteria inside club cells raises the possibility that the alarm substance may contain a bacterial component. Indeed, lysate from a zebrafish Staphylococcus isolate is sufficient to elicit alarm behaviour, acting in concert with a substance from fish. These results suggest that Schreckstoff, which allows one individual to unwittingly change the emotional state of the surrounding population, derives from two kingdoms and is associated with processes that protect the host from bacteria.


Assuntos
Comunicação Animal , Pele/metabolismo , Staphylococcus/metabolismo , Peixe-Zebra/fisiologia , Animais , Animais Geneticamente Modificados , Medo/fisiologia , Células Gigantes/metabolismo , Células Gigantes/microbiologia , Microscopia Intravital , Muco/citologia , Muco/metabolismo , Muco/microbiologia , Neutrófilos/metabolismo , Neutrófilos/microbiologia , Imagem Óptica , Reflexo de Sobressalto/fisiologia , Pele/citologia , Pele/microbiologia , Simbiose/fisiologia , Peixe-Zebra/lesões , Peixe-Zebra/microbiologia
15.
Nat Commun ; 10(1): 3827, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444357

RESUMO

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown etiology. Although defects in nucleocytoplasmic transport (NCT) may be central to the pathogenesis of ALS and other neurodegenerative diseases, the molecular mechanisms modulating the nuclear pore function are still largely unknown. Here we show that genetic and pharmacological modulation of actin polymerization disrupts nuclear pore integrity, nuclear import, and downstream pathways such as mRNA post-transcriptional regulation. Importantly, we demonstrate that modulation of actin homeostasis can rescue nuclear pore instability and dysfunction caused by mutant PFN1 as well as by C9ORF72 repeat expansion, the most common mutation in ALS patients. Collectively, our data link NCT defects to ALS-associated cellular pathology and propose the regulation of actin homeostasis as a novel therapeutic strategy for ALS and other neurodegenerative diseases.


Assuntos
Actinas/metabolismo , Esclerose Amiotrófica Lateral/patologia , Neurônios Motores/patologia , Poro Nuclear/patologia , Profilinas/metabolismo , Acrilamidas/farmacologia , Actinas/ultraestrutura , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Transporte Ativo do Núcleo Celular/genética , Esclerose Amiotrófica Lateral/genética , Biópsia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Proteína C9orf72/genética , Proteína C9orf72/metabolismo , Linhagem Celular , Córtex Cerebral/citologia , Córtex Cerebral/patologia , Embrião de Mamíferos , Fibroblastos , Humanos , Microscopia Eletrônica de Transmissão , Neurônios Motores/citologia , Mutação , Poro Nuclear/efeitos dos fármacos , Poro Nuclear/ultraestrutura , Cultura Primária de Células , Profilinas/genética , Multimerização Proteica/efeitos dos fármacos , Multimerização Proteica/genética , Pele/citologia , Pele/patologia , Tiazóis/farmacologia , Tiazolidinas/farmacologia
16.
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
17.
Clin Dermatol ; 37(4): 326-335, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31345320

RESUMO

The world population of adults aged 60 years or more is increasing globally, and this development can impact skin disease morbidity and mortality, as well as being reflected in the health care system organization. There is substantial evidence that the burden from a remarkable number of skin nonmalignant and malignant conditions is greater in the elderly. Dermatologic research and clinical education in dermatology should focus on both challenges and opportunities created by aging. Skin aging due to intrinsic and extrinsic factors can alter significantly epidermal and dermal structure and functions. Dermal aging can be linked to a great number of complications in routine dermatologic conditions, with slow healing as an example of a severe complication in the elderly. This may be attributed to aged dermal fibroblasts modifying the tissue microenvironment via a shift in their soluble factors and extracellular matrix repertoire. This senescence-associated secretory phenotype can explain the particular proclivity of aged skin to develop malignancies.


Assuntos
Envelhecimento da Pele , Dermatopatias/etiologia , Fatores Etários , Fibroblastos , Humanos , Pele/citologia , Envelhecimento da Pele/fisiologia , Cicatrização
18.
Mater Sci Eng C Mater Biol Appl ; 103: 109750, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31349498

RESUMO

Stents used for cardiovascular applications are composed of three main elements; a metal, polymer coating and the specific drug component. Nickel-based metals and polymer coatings currently used in the stent market have increased the recurrence of in-stent restenosis and stent failure due to inflammation. In this study, a Ti-8Mn alloy was used to fabricate a nanostructured surface that can be used for drug eluting stents to overcome the hypersensitivity of metals that are currently used in stent making as well as introducing a new built-in nano-drug reservoir instead of polymer coatings. Two different systems were studied: titanium dioxide nanotubes (NTs) and Ti-8Mn oxides NTs. The materials were characterized using field emission electron microscope (FESEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), roughness, wettability and surface energy measurements. Nanoindentation was used to evaluate the mechanical properties of the nanotubes as well as their stability. In-vitro cytotoxicity and cell proliferation assays were used to study the effect of the nanotubes on cell viability. Computational insights were also used to test the blood compatibility using band gap model analysis, comparing the band gap of the materials under investigation with that of the fibrinogen, in order to study the possibility of charge transfer that affects the blood clotting mechanism. In addition, the drug loading capacity of the materials was studied using acetyl salicylic acid as a drug model.


Assuntos
Stents Farmacológicos , Nanotubos/química , Ligas/química , Animais , Aspirina/farmacocinética , Células Cultivadas , Teoria da Densidade Funcional , Módulo de Elasticidade , Manganês/química , Camundongos , Microscopia Eletrônica de Varredura , Níquel , Oxirredução , Espectroscopia Fotoeletrônica , Pele/citologia , Espectrometria por Raios X , Propriedades de Superfície , Titânio , Molhabilidade , Difração de Raios X
19.
Mol Med Rep ; 20(3): 2294-2302, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31322186

RESUMO

All­trans retinoic acid (ATRA) can protect fibroblasts against ultraviolet (UV)­induced oxidative damage, however, its underlying molecular mechanism is still unclear. The present study aimed to investigate the role of 3­hydroxy­3­methylglutaryl reductase degradation (Hrd1) in the protective effect of ATRA on human skin fibroblasts exposed to UV. The expression of Hrd1 in human or mice skin was assessed by immunohistochemistry (IHC) staining and western blot analysis. Hrd1 siRNA (si­Hrd1) and Hrd1 recombinant adenoviruses (Ad­Hrd1) were used to downregulate and upregulate Hrd1 expression in fibroblasts, respectively. The interaction between Hrd1 and NF­E2­related factor 2 (Nrf2) was assessed by co­immunoprecipitation (co­IP) and immunofluorescence analysis. The results revealed that Hrd1 expression was increased but Nrf2 expression was decreased in UV­exposed human skin fibroblasts. In addition, ATRA could reverse the increase of Hrd1 expression induced by UV radiation in vivo and in vitro. ATRA or knockdown of Hrd1 could increase Nrf2 expression in fibroblasts exposed to UV radiation, and Hrd1 could directly interact with Nrf2 in skin fibroblasts. Notably, overexpression of Hrd1 abolished the protective effect of ATRA on the UV­induced decrease of Nrf2 expression, the production of reactive oxygen species (ROS) and the decrease of cell viability. In conclusion, the present data demonstrated that ATRA protected skin fibroblasts against UV­induced oxidative damage through inhibition of E3 ligase Hrd1.


Assuntos
Fibroblastos/efeitos dos fármacos , Protetores contra Radiação/farmacologia , Tretinoína/farmacologia , Ubiquitina-Proteína Ligases/genética , Raios Ultravioleta/efeitos adversos , Adulto , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/efeitos da radiação , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Humanos , Masculino , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Pele/citologia , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/efeitos da radiação , Ubiquitina-Proteína Ligases/análise , Ubiquitina-Proteína Ligases/metabolismo
20.
Med Phys ; 46(9): 4046-4056, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31315162

RESUMO

PURPOSE: Identification of morphological characteristics of skin lesions is of vital importance in diagnosing diseases with dermatological manifestations. This task is often performed manually or in an automated way based on intensity level. Recently, ultra-broadband raster-scan optoacoustic mesoscopy (UWB-RSOM) was developed to offer unique cross-sectional optical imaging of the skin. A machine learning (ML) approach is proposed here to enable, for the first time, automated identification of skin layers in UWB-RSOM data. MATERIALS AND METHODS: The proposed method, termed SkinSeg, was applied to coronal UWB-RSOM images obtained from 12 human participants. SkinSeg is a multi-step methodology that integrates data processing and transformation, feature extraction, feature selection, and classification. Various image features and learning models were tested for their suitability at discriminating skin layers including traditional machine learning along with more advanced deep learning algorithms. An support vector machines-based postprocessing approach was finally applied to further improve the classification outputs. RESULTS: Random forest proved to be the most effective technique, achieving mean classification accuracy of 86.89% evaluated based on a repeated leave-one-out strategy. Insights about the features extracted and their effect on classification accuracy are provided. The highest accuracy was achieved using a small group of four features and remained at the same level or was even slightly decreased when more features were included. Convolutional neural networks provided also promising results at a level of approximately 85%. The application of the proposed postprocessing technique was proved to be effective in terms of both testing accuracy and three-dimensional visualization of classification maps. CONCLUSIONS: SkinSeg demonstrated unique potential in identifying skin layers. The proposed method may facilitate clinical evaluation, monitoring, and diagnosis of diseases linked to skin inflammation, diabetes, and skin cancer.


Assuntos
Inteligência Artificial , Processamento de Imagem Assistida por Computador/métodos , Técnicas Fotoacústicas , Pele/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Automação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pele/citologia
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