RESUMEN
BACKGROUND: Olive (Olea europaea Linn) leaves contain a phenolic compound oleuropein (Ole) has antioxidant, anti-inflammatory, and immunomodulatory activities. However, whether Ole might be an effective treatment for atopic dermatitis (AD) remains unknown. OBJECTIVE: This study investigated the functional role of oleuropein in a 2,4-dinitrochlorobenzene-induced AD-like mouse model, with a focus on allergic inflammation. METHODS: We evaluated cytokine gene expression, COX-2 inflammatory protein production, and Th2 related cytokine regulation of mast cells and eosinophils that infiltrated AD-like skin lesions. RESULTS: A topical application of Ole significantly reduced Th2-related cytokine gene expression (IL-4 and IL-5) and inflammatory COX-2 protein production in AD-like skin lesions. Additionally, Ole suppressed serum IgE levels. Furthermore, Ole effectively reduced ear swelling and epidermal and dermal thickening. CONCLUSIONS: These results suggested that, mechanistically, Ole treatment improved allergic inflammation by blocking the Th2-driven inflammatory axis. In conclusion, our findings indicated that Ole showed promise in treating AD by regulating serum IgE and Th2 cytokine levels. Although the effects of Ole on AD in humans require clinical trials, our results provided insights into how AD treatments might be improved.
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Poor prognosis due to the high relapse and metastasis rates of breast cancer has been particularly linked to the luminal B subtype. The current study utilized MCF-7 and ZR-75-1 to investigate various luminal subtypes of breast cancers that have discrepant expressions in the estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). Understanding of the differential protein profiles and the associated pathways could help alleviate the malignance and promote the long-term survival rate of breast cancer patients. Functional proteome tools were applied to comprehensively delineate the global protein alterations that reflect the varieties of biological features between the two subtypes. In this study, a total of 11 proteins with significant and meaningful changes were identified. These protein targets including PRX2, CK19, nucleophosmin and cathepsin D were mostly involved in cell differentiation or proliferation. Particularly, cathepsin D was highly expressed in the luminal B subtype. Moreover, the level of cathepsin-D was also upregulated in the clinical metastatic tissues. Accordingly, the RNA interference-mediated silencing of cathepsin D stimulated ER expression but suppressed the level of HER2. The knockdown of cathepsin D enhanced the level of ZO-1 and a remarkable decrease in N-cadherin was also detected. Again, the matrix metalloproteinases (MMP) activity was impaired under the cathepsin D abolishment. Collectively, this study represented a modality to explore novel relationships in a proteome complex and highlighted the functional roles of cathepsin D in treatment options for different subtypes of breast cancer.
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Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Recurrencia Local de Neoplasia/diagnóstico , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/clasificación , Catepsina D/metabolismo , Femenino , Humanos , Metástasis Linfática , Células MCF-7 , Recurrencia Local de Neoplasia/metabolismo , Pronóstico , Proteoma/análisis , Proteoma/metabolismo , Proteómica/métodos , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Células Tumorales CultivadasRESUMEN
Atopic dermatitis (AD) is a recurrent allergic skin disease caused by genetic and environmental factors. Patients with AD may experience immune imbalance, increased levels of mast cells, immunoglobulin (Ig) E and pro-inflammatory factors (Cyclooxygenase, COX-2 and inducible NO synthase, iNOS). While spilanthol (SP) has anti-inflammatory and analgesic activities, its effect on AD remains to be explored. To develop a new means of SP, inflammation-related symptoms of AD were alleviated, and 2,4-dinitrochlorobenzene (DNCB) was used to induce AD-like skin lesions in BALB/c mice. Histopathological analysis was used to examine mast cells and eosinophils infiltration in AD-like skin lesions. The levels of IgE, IgG1 and IgG2a were measured by enzyme-linked immunosorbent assay (ELISA) kits. Western blot was used for analysis of the mitogen-activated protein kinase (MAPK) pathways and COX-2 and iNOS protein expression. Topical SP treatment reduced serum IgE and IgG2a levels and suppressed COX-2 and iNOS expression via blocked mitogen-activated protein kinase (MAPK) pathways in DNCB-induced AD-like lesions. Histopathological examination revealed that SP reduced epidermal thickness and collagen accumulation and inhibited mast cells and eosinophils infiltration into the AD-like lesions skin. These results indicate that SP may protect against AD skin lesions through inhibited MAPK signaling pathways and may diminish the infiltration of inflammatory cells to block allergic inflammation.
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Antialérgicos/uso terapéutico , Antiinflamatorios/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Alcamidas Poliinsaturadas/uso terapéutico , Animales , Antialérgicos/administración & dosificación , Antialérgicos/farmacología , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Dermatitis Atópica/etiología , Dermatitis Atópica/metabolismo , Dinitroclorobenceno/toxicidad , Femenino , Inmunoglobulinas/genética , Inmunoglobulinas/metabolismo , Ratones , Ratones Endogámicos BALB C , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Alcamidas Poliinsaturadas/administración & dosificación , Alcamidas Poliinsaturadas/farmacologíaRESUMEN
The skin provides protection against environmental stress. However, intrinsic and extrinsic aging causes significant alteration to skin structure and components, which subsequently impairs molecular characteristics and biochemical processes. Here, we have conducted an immunohistological investigation and established the proteome profiles on nude mice skin to verify the specific responses during aging caused by different factors. Our results showed that UVB-elicited aging results in upregulation of proliferating cell nuclear antigen and strong oxidative damage in DNA, whereas chronological aging abolished epidermal cell growth and increased the expression of caspase-14, as well as protein carbonylation. Network analysis indicated that the programmed skin aging activated the ubiquitin system and triggered obvious downregulation of 14-3-3 sigma, which might accelerate the loss of cell growth capacity. On the other hand, UVB stimulation enhanced inflammation and the risk of skin carcinogenesis. Collectively, functional proteomics could provide large-scale investigation of the potent proteins and molecules that play important roles in skin subjected to both intrinsic and extrinsic aging.
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Mapas de Interacción de Proteínas , Proteoma/metabolismo , Envejecimiento de la Piel , Piel/metabolismo , Proteínas 14-3-3/análisis , Proteínas 14-3-3/metabolismo , Envejecimiento , Animales , Diferenciación Celular/efectos de la radiación , Proliferación Celular/efectos de la radiación , Femenino , Ratones Desnudos , Estrés Oxidativo/efectos de la radiación , Proteoma/análisis , Proteómica , Piel/química , Piel/efectos de la radiación , Piel/ultraestructura , Ubiquitinas/análisis , Ubiquitinas/metabolismo , Rayos UltravioletaRESUMEN
BACKGROUND: Laser pretreatment of skin can be used to enable drugs used in dermatology to penetrate the skin to the depth necessary for their effect to take place. OBJECTIVE: To compare the permeation of tranexamic acid after conventional non-fractionated ablative Er:YAG and CO2 laser pretreatment in a laser-aided transdermal delivery system. MATERIALS AND METHODS: An erbium-doped yttrium aluminium garnet (Er:YAG) and a CO2 laser were used to pretreat dorsal porcine skin. Scanning electron microscopy was used to examine disruption of the skin surface. Confocal laser scanning microscopy was used to determine the depth of penetration of a reporter molecule (fluorescein isothiocyanate) into the skin. A Franz diffusion assembly was used to examine fluency-related increases in transdermal delivery of transexamic acid. RESULTS: Transdermal delivery of tranexamic acid increased as Er:YAG laser fluency increased. Transdermal delivery was higher when CO2 laser pretreatment was used than when Er:YAG laser pretreatment was used, but a "ceiling effect" was present and increasing the wattage did not cause a further increase in delivery. CO2 laser pretreatment also caused more extensive and deeper skin disruption than Er:YAG laser pretreatment. CONCLUSION: For conventional, non-fractionated ablative laser pretreatment, the Er:YAG laser would be an optimal choice to enhance transdermal penetration of transexamic acid.
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Láseres de Gas/uso terapéutico , Láseres de Estado Sólido/uso terapéutico , Preparaciones para Aclaramiento de la Piel/administración & dosificación , Preparaciones para Aclaramiento de la Piel/farmacocinética , Ácido Tranexámico/administración & dosificación , Ácido Tranexámico/farmacocinética , Administración Cutánea , Animales , Sistemas de Liberación de Medicamentos , Microscopía Confocal , Microscopía Electrónica de Rastreo , Permeabilidad , Piel/metabolismo , Piel/ultraestructura , Fenómenos Fisiológicos de la Piel , PorcinosRESUMEN
BACKGROUND: Topical vitamin C derivatives have been used to treat melasma and used as a skin whitener. The aim of this study was to compare skin histology and permeation of l-ascorbic acid 2-phosphate sesquimagnesium salt (MAP-1) and magnesium l-ascorbic acid-2-phosphate (MAP-2) after fractional CO2 laser pretreatment. METHODS: The effect of fractional laser treatment on porcine skin was examined by scanning electron microscopy and confocal laser scanning electron microscopy. The effect of fractional CO2 laser treatment of different fluencies and pass numbers on transdermal flux of the two vitamin C derivatives through porcine skin was examined in vitro using a Franz diffusion chamber. RESULTS: Fluxes of MAP-1 and MAP-2 across fractional CO2 laser-treated (5 W) skin were eight- to 13-fold, and 20- to 22-fold higher, respectively, than the fluxes of these compounds across intact skin. Fluxes of MAP-1 and MAP-2 across fractional CO2 laser-treated (9 W) skin were 14- to 19-fold, and 30- to 42-fold higher, respectively, than their fluxes across intact skin. CONCLUSION: Fractional CO2 laser treatment is an effective way of delivering vitamin C derivatives into the skin.
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Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/farmacocinética , Láseres de Gas , Absorción Cutánea/efectos de la radiación , Animales , Ácido Ascórbico/análogos & derivados , Permeabilidad/efectos de la radiación , Piel/metabolismo , Piel/efectos de la radiación , PorcinosRESUMEN
BACKGROUND: Topical tranexamic acid has been used to treat melasma and as a skin whitener. OBJECTIVE: The aim of this study was to compare the skin histology and permeation of tranexamic acid after fractional and conventional CO2 laser pretreatment. METHODS: The effect of treatment with different strengths of fractional and conventional CO2 laser treatment was examined by scanning and transmission electron microscopy. Permeation of tranexamic acid through porcine skin was tested in vitro using a Franz diffusion chamber. RESULTS: Four passes of fractional laser treatment caused less skin damage than conventional laser treatment at the same fluency. Fractional laser treatment caused at least 85% of the cumulative tranexamic aid permeation at the same fluency, and as fluency increased, the number of passes needed to achieve this goal decreased. CONCLUSION: Fractional laser treatment is as effective as conventional laser treatment in enhancing tranexamic acid delivery and causes less skin damage.
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Fármacos Dermatológicos/administración & dosificación , Permeabilidad/efectos de la radiación , Absorción Cutánea/efectos de la radiación , Piel/patología , Ácido Tranexámico/administración & dosificación , Administración Cutánea , Animales , Fraccionamiento de la Dosis de Radiación , Láseres de Gas , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Permeabilidad/efectos de los fármacos , Piel/efectos de los fármacos , Piel/efectos de la radiación , Absorción Cutánea/efectos de los fármacos , PorcinosRESUMEN
Lead compounds exhibit a high degree of cytotoxicity and carcinogenicity. We evaluated the impact of lead acetate on the liver by skin exposure as well as the changes in protein profiles reflecting pathogenic processes. Functional proteomic tools showed that the most meaningful protein changes were involved in protein folding, ER stress, and apoptosis in the presence of an organic lead compound. Treatment with lead acetate also elicits intracellular ROS levels as well as carbonyl modification of chaperone proteins, suggesting that lead might trigger the unfolded protein response due to oxidative stress. Lead application induced ER stress, as indicated by the promotion of GRP78 and by increased expression of the transcription factors ATF6, IRE1α, and PERK. Moreover, upregulation of GRP75 may participate in lead-caused hepatic cytotoxicity while abrogation of GRP75 appears to attenuate the inhibition of cell growth. Our findings demonstrate that accumulation of organic lead in the liver can induce oxidative imbalance and protein impairment that may result in ER stress followed by liver injuries. Hepatic proteome profiles delineate a finer picture of protein networks and metabolic pathways primarily involved in lead-initiated hepatic toxicity via skin exposure.
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Hígado/efectos de los fármacos , Hígado/patología , Compuestos Organometálicos/toxicidad , Proteínas/metabolismo , Administración Tópica , Animales , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Hígado/metabolismo , Ratones Endogámicos BALB C , Ratones Desnudos , Compuestos Organometálicos/administración & dosificación , Compuestos Organometálicos/metabolismo , Carbonilación Proteica/efectos de los fármacos , Mapas de Interacción de Proteínas/efectos de los fármacos , Proteínas/análisis , Proteómica , Piel/metabolismo , Respuesta de Proteína Desplegada/efectos de los fármacosRESUMEN
Punicalagin (PUN) was isolated from the peel of pomegranate (Punica granatum L.), is a polyphenol with anti-inflammatory, hepatoprotective, and antioxidant activities. However, it remains unclear whether PUN alleviates the inflammation and anti-inflammatory mechanisms in pro-inflammatory cytokines-induced human keratinocyte HaCaT cells. Here, we investigated that tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) mixture-stimulated HaCaT cells were treated with various concentrations of PUN, followed by analyzed the expression of inflammation-related mediators and evaluate anti-inflammatory-related pathways. Our results demonstrated that PUN ≤ 100 µM did not reduce HaCaT cell viability, and PUN ≥ 3 µM was sufficient to decrease interleukin-6 (IL-6), IL-8, monocyte chemoattractant protein-1 (MCP-1), chemokine ligand 5 (CCL5), CCL17 and CCL20 concentrations. We found that PUN ≥ 10 µM and ≥ 3 µM significantly increased sirtuin 1 (SIRT1) expression and inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation, respectively. PUN downregulated inflammation-related proteins cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), enhanced nuclear factor erythroid-2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) expression. Moreover, PUN decreased intercellular adhesion molecule-1 (ICAM-1) expression and inhibited monocyte adhesion to inflamed HaCaT cells. PUN also suppressed inflammatory-related pathways, including mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways in TNF-α/IFN-γ- stimulated HaCat cells. Collectively, there is significant evidence that PUN has effective protective defenses against TNF-α/IFN-γ-induced skin inflammation by enhancing SIRT1 to mediate STAT3 and Nrf2/HO-1 signaling pathway.
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Taninos Hidrolizables , Granada (Fruta) , Factor de Necrosis Tumoral alfa , Humanos , Factor de Necrosis Tumoral alfa/metabolismo , Sirtuina 1/metabolismo , Interferón gamma/metabolismo , Granada (Fruta)/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Hemo-Oxigenasa 1/metabolismo , Células HaCaT , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , FN-kappa B/metabolismo , Antiinflamatorios/uso terapéutico , Inflamación/metabolismoRESUMEN
Cervix cancer is the second most common cancer among women worldwide, whereas paclitaxel, the first line chemotherapeutic drug used to treat cervical cancer, shows low chemosensitivity on the advanced cervical cancer cell line. Tanshinone IIA (Tan IIA) exhibited strong growth inhibitory effect on CaSki cells (IC50 = 5.51 µM) through promoting caspase cascades with concomitant upregulating the phosphorylation of p38 and JNK signaling. Comprehensive proteomics revealed the global protein changes and the network analysis implied that Tan IIA treatment would activate ER stress pathways that finally lead to apoptotic cell death. Moreover, ER stress inhibitor could alleviate Tan IIA caused cell growth inhibition and ameliorate C/EBP-homologous protein as well as apoptosis signal-regulating kinase 1 mediated cell death. The therapeutic interventions targeting the mitochondrial-related apoptosis and ER stress responses might be promising strategies to conquer paclitaxel resistance.
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Abietanos/farmacología , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Proteoma/metabolismo , Adulto , Anciano , Secuencia de Aminoácidos , Línea Celular Tumoral , Femenino , Humanos , Concentración 50 Inhibidora , Persona de Mediana Edad , Datos de Secuencia Molecular , Estrés Oxidativo , Paclitaxel/farmacología , Proteoma/química , Transducción de Señal , Neoplasias del Cuello UterinoRESUMEN
Hepatic ischemia-reperfusion (IR) injury is a common clinical problem and ROS may be a contributing factor on IR injury. The current study evaluates the potential protective effect of saffron ethanol extract (SEE) in a rat model upon hepatic IR injury. Caspases 3 and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL) results showed increased cell death in the IR samples; reversely, minor apoptosis was detected in the SEE/IR group. Pretreatment with SEE significantly restored the content of antioxidant enzymes (SOD1 and catalase) and remarkably inhibited the intracellular ROS concentration in terms of reducing p47phox translocation. Proteome tools revealed that 20 proteins were significantly modulated in protein intensity between IR and SEE/IR groups. Particularly, SEE administration could attenuate the carbonylation level of several chaperone proteins. Network analysis suggested that saffron extract could alleviate IR-induced ER stress and protein ubiquitination, which finally lead to cell apoptosis. Taken together, SEE could reduce hepatic IR injury through modulating protein oxidation and our results might help to develop novel therapeutic strategies against ROS-caused diseases.
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Crocus/química , Hepatopatías/metabolismo , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Proteoma/metabolismo , Daño por Reperfusión/metabolismo , Animales , Catalasa/análisis , Catalasa/metabolismo , Electroforesis en Gel Bidimensional , Etanol , Histocitoquímica , Etiquetado Corte-Fin in Situ , Hígado/química , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Carbonilación Proteica , Proteínas/análisis , Proteínas/metabolismo , Proteoma/análisis , Proteómica , Ratas , Ratas Wistar , Superóxido Dismutasa/análisis , Superóxido Dismutasa/metabolismo , Proteínas UbiquitinadasRESUMEN
The objective of this study was to investigate the effects of two lasers (Er:YAG and CO2) in enhancing skin permeation of three vitamin C derivatives, L-ascorbic acid 2-phosphate sesquimagnesium salt (MAP-1), magnesium L-ascorbic acid-2-phosphate (MAP-2), and 2-phospho-L-ascorbic acid trisodium salt (SAP). Dorsal skin of 1-week-old pathogen-free pigs was used for this in vitro study. Changes in permeation in laser-treated skin treated by the lasers were examined by confocal scanning electron microscopy. Transdermal flux of vitamin C derivatives was examined with a Franz diffusion cell. Fluxes of MAP-1, MAP-2, and SAP across Er:YAG laser-treated skin were 15-27-fold, 48-123-fold, and 22-56-fold higher, respectively, than their fluxes across intact skin. The fluxes of MAP-1, MAP-2, and SAP across CO2 laser-treated skin were 28-36-fold, 116-156-fold, and 79-102-fold higher, respectively, than their fluxes across intact skin. Optimal fluency for the Er:YAG laser was 3.8 J/cm(2) for MAP-1 and 5 J/cm(2) for MAP-2 and SAP. Optimal fluency for the CO2 laser was 5 W for all three derivatives. In conclusion, optimal fluency for all derivatives was 5 W for the CO2 laser and 3.8 to 5 J/cm(2) for the Er:YAG laser.
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Ácido Ascórbico/análogos & derivados , Láseres de Gas , Láseres de Estado Sólido , Piel/efectos de los fármacos , Piel/efectos de la radiación , Administración Cutánea , Animales , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/farmacocinética , Técnicas In Vitro , Microscopía Confocal , Microscopía Electrónica de Rastreo , Permeabilidad/efectos de la radiación , Piel/metabolismo , PorcinosRESUMEN
BACKGROUND: Topical treatment with vitamin C has been used to treat photoaged skin and as a skin whitener, but no standard procedure exists for percutaneous delivery. OBJECTIVE: To compare skin histology and the permeation of ascorbic acid 2-glucoside (AA2G) after fractional and conventional carbon dioxide (CO(2) ) laser pretreatment. METHODS: The effect on porcine skin of treatment with different strengths of fractional and conventional CO(2) laser treatment was examined using scanning electron microscopy and transmission electron microscopy. Permeation of AA2G through porcine skin was tested in vitro using a Franz diffusion chamber. In vivo changes in fluorescein thiocyanate permeability in nude mice were examined using confocal laser scanning microscopy. RESULTS: Fractional CO(2) laser treatment with four or fewer passes caused less disruption than conventional laser treatment at the same fluence. AA2G permeation using four passes of fractional laser treatment was similar to that seen with conventional CO(2) laser treatment of the same fluence. Changes in permeability and in depth of permeation were higher with conventional than fractional laser treatment. CONCLUSION: Fractional CO(2) laser treatment can cause similar transdermal delivery of AA2G to conventional laser treatment with less skin disruption and a different pattern of histologic change.
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Ácido Ascórbico/análogos & derivados , Láseres de Gas , Absorción Cutánea/efectos de la radiación , Piel/ultraestructura , Administración Cutánea , Animales , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/farmacocinética , Femenino , Técnicas In Vitro , Ratones , Ratones Desnudos , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Piel/efectos de la radiación , Sus scrofaRESUMEN
Proinflammatory mediators such as interleukin (IL)-1ß cause retinal pigment epithelium (RPE) inflammation, which is related to visual deterioration, including age-related macular degeneration and diabetic retinopathy. Oleuropein is a polyphenol compound that shows potent anti-inflammatory, antioxidant, and anti-cancer activities, but its effects on IL-1ß-induced inflammation have not been examined in the adult RPE cell line ARPE-19. Here, we assessed the ability of oleuropein to attenuate this inflammation in ARPE-19 cells. IL-1ß induced secretion of the inflammatory cytokines IL-6, monocyte chemoattractant protein-1 (MCP)-1, and soluble intercellular adhesion molecule (sICAM)-1. As measured by enzyme-linked immunosorbent assay, oleuropein significantly inhibited levels of all three proteins and led to decreased monocyte adhesiveness to ARPE-19 cells. To clarify the underlying anti-inflammatory mechanisms, we used western blots to evaluate the effect of oleuropein on inactivation of the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. The results showed that oleuropein significantly decreased levels of the inflammatory mediator cyclooxygenase-2 and increased anti-inflammatory protein HO-1 expression. We next examined if the anti-inflammatory activity of oleuropein arises via inactivated NF-κB. We found that suppressing phosphorylation of the JNK1/2 and p38 MAPK signaling pathways inhibited IL-6, MCP-1, and sICAM-1 secretion, implicating these pathways and NF-κB suppression in the effects of oleuropein. These results indicate that oleuropein shows potential for the prevention and treatment of inflammatory diseases of the retina.
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Antiinflamatorios/farmacología , Células Epiteliales/efectos de los fármacos , Glucósidos Iridoides/farmacología , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Epitelio Pigmentado de la Retina/efectos de los fármacos , Retinitis/tratamiento farmacológico , Adulto , Antiinflamatorios/uso terapéutico , Biomarcadores/metabolismo , Línea Celular , Células Epiteliales/metabolismo , Humanos , Interleucina-1beta , Glucósidos Iridoides/uso terapéutico , Epitelio Pigmentado de la Retina/metabolismo , Retinitis/inducido químicamente , Retinitis/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
The objective of this study is to investigate the effects of two lasers (erbium:YAG and CO(2)) on the ability to enhance skin permeation of two vitamin C derivatives, 3-O-ethyl ascorbic acid (EAC) and ascorbic acid 2-glucoside (AA2G). The study was taken in the skin of a female nude mouse (Balb/c-nu strain, 8 weeks old) in vitro. The histologic and ultrastructural changes of the nude mouse skin treated by the lasers were examined under light microscopy and transmission electron microscopy, respectively. The in vitro permeation of vitamin C derivatives was performed in Franz cell. The stratum corneum (SC) layer in the skin was partly ablated by erbium:YAG laser treatment, resulting in greater permeation of both vitamin C derivatives. The flux of EAC and AA2G across erbium:YAG laser-treated skin was 105 to 189-fold and 35 to 78-fold higher, respectively, than their flux across intact skin. The increase in enhancement ratio with increase in fluency decreases markedly for both compounds at the last dose escalation (from 5.0 to 6.3 J/cm(2)). Both SC ablation and a thermal effect may contribute to the effect of the CO(2) laser on skin structure. The flux of EAC and AA2G across CO(2) laser-treated skin was 181 to 277-fold and 82 to 117-fold higher, respectively, than their flux across intact skin. We concluded that both erbium:YAG and CO(2) laser pretreatment increased the transdermal flux of two stable vitamin C derivatives, EAC and AA2G. The optimal fluency for the Er:YAG laser was 5 J/cm(2).
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Ácido Ascórbico/análogos & derivados , Láseres de Gas/uso terapéutico , Láseres de Estado Sólido/uso terapéutico , Piel/metabolismo , Piel/efectos de la radiación , Administración Cutánea , Animales , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/farmacocinética , Femenino , Técnicas In Vitro , Ratones , Ratones Desnudos , Permeabilidad/efectos de la radiación , Piel/efectos de los fármacosRESUMEN
Spilanthol has been reported to possess antioxidant, antiinflammatory, antimicrobial and antinociceptive properties. At present, the literature has reported the beneficial role of spilanthol on tumor necrosis factorα (TNFα)stimulated HaCaT cells. The present study investigated the effects of spilanthol on the expression of TNFαinduced intercellular adhesion molecule 1 (ICAM1) and cyclooxygenase (COX)2 in the human keratinocyte cell line HaCaT. Cells were pretreated with various concentrations of spilanthol (10150 µM) followed by TNFα to induce inflammation. Pretreatment with spilanthol decreased TNFαinduced COX2 expression by western blotting and suppressed the expression of proinflammatory mediators, including interleukin (IL)6, IL8 and monocyte chemotactic protein 1 using ELISA. Spilanthol also decreased the expression of TNFαinduced ICAM1 protein and mRNA assay by western blotting and RTqPCR, respectively, in addition to the monocyte adhesiveness of HaCaT cells. Furthermore, spilanthol significantly suppressed the phosphorylation of cJun Nterminal kinase (JNK), while pretreatment with spilanthol enhanced heme oxygenase (HO)1 protein expression by western blotting. These results demonstrated that spilanthol may exert its antiinflammatory activity by suppressing the TNFαinduced expression of ICAM1, COX2 and proinflammatory mediators by enhancing that of HO1, and inhibiting the activation of the phosphorylated JNK signaling pathway. It is hypothesized that spilanthol may be a natural antiinflammatory drug to attenuate skin inflammatory disease.
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Regulación de la Expresión Génica/efectos de los fármacos , Hemo-Oxigenasa 1/genética , Molécula 1 de Adhesión Intercelular/genética , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Queratinocitos/metabolismo , Alcamidas Poliinsaturadas/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Adhesión Celular/efectos de los fármacos , Línea Celular , Ciclooxigenasa 2/metabolismo , Citocinas/metabolismo , Hemo-Oxigenasa 1/metabolismo , Humanos , Inflamación/genética , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Queratinocitos/efectos de los fármacos , Monocitos/metabolismo , ARN Mensajero/genética , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Osthole is found in Cnidium monnieri (L.) and has anti-inflammatory and anti-oxidative properties. It also inhibits the proliferation of hepatocellular carcinoma cells. This study aimed to evaluate the osthole suppressive nonalcoholic fatty liver disease effects in oleic acid (OA)-induced hepatic steatosis and if it can modulate inflammatory responses and oxidative stress. FL83B cells were pretreated with OA (250µΜ) for 24h, and then added different concentrations of osthole (3-100µM) for 24h. Subsequently, lipolysis and transcription factors of adipogenesis and phosphorylation of AMP-activated protein kinase proteins were measured. In addition, cells with OA-induced steatosis were H2O2-stimulated, and then incubated with osthole to evaluated if it could suppress its progression to steatohepatitis. Osthole significantly enhanced glycerol release and lipolysis protein expression. Osthole also promoted phosphorylation of AMP-activated protein kinases and increased the activity of triglyceride lipase and hormone- sensitive lipase. Osthole suppressed the nuclear transcription factor kappa-B and the p38 mitogen-activated protein kinase pathway, and decreased the malondialdehyde concentration in FL83B cells with OA-induced steatosis that were treated with H2O2. These results suggest that osthole might suppress nonalcoholic fatty liver disease by decreasing lipid accumulation, and through its anti-oxidative and anti-inflammatory effects via blocked NF-κB and MAPK signaling pathways.
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Antioxidantes/metabolismo , Cumarinas/farmacología , Mediadores de Inflamación/metabolismo , Lípidos/química , Proteínas Quinasas Activadas por AMP/metabolismo , Adipogénesis/efectos de los fármacos , Adipogénesis/genética , Animales , Muerte Celular/efectos de los fármacos , Línea Celular , Cumarinas/química , Ciclooxigenasa 2/metabolismo , Ácido Graso Sintasas/metabolismo , Hígado Graso/patología , Regulación de la Expresión Génica/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Peróxido de Hidrógeno/toxicidad , Lipólisis/efectos de los fármacos , Lipólisis/genética , Ratones , FN-kappa B/metabolismo , Fosforilación/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Transcripción/metabolismoRESUMEN
Influenza virus remains an emerging virus and causes pandemics with high levels of fatality. After screening different plant extracts with potential anti-influenza activity, a water extract of Taxodium distichum stems (TDSWex) showed excellent activity against influenza viruses. The EC50 of TDSWex was 0.051 ± 0.024 mg/mL against influenza virus A/WSN/33. TDSWex had excellent antiviral efficacy against various strains of human influenza A and B viruses, particularly oseltamivir-resistant clinical isolates and a swine-origin influenza strain. We observed that the synthesis of viral RNA and protein were inhibited in the presence of TDSWex. The results of the time-of-addition assay suggested that TDSWex inhibited viral entry and budding. In the hemagglutination inhibition assay, TDSWex inhibited the hemagglutination of red blood cells, implying that the extract targeted hemagglutin-related functions such as viral entry. In the attachment and penetration assay, TDSWex showed antiviral activity with EC50s of 0.045 ± 0.026 and 0.012 ± 0.003 mg/mL, respectively. In addition, TDSWex blocked neuraminidase activity. We conclude that TDSWex has bimodal activities against both hemagglutinin and neuraminidase during viral replication.
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Hemaglutininas/metabolismo , Neuraminidasa/metabolismo , Orthomyxoviridae/metabolismo , Extractos Vegetales/metabolismo , Taxodium/química , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Perros , Hemaglutininas/química , Humanos , Células de Riñón Canino Madin Darby , Microscopía Fluorescente , Neuraminidasa/antagonistas & inhibidores , Orthomyxoviridae/enzimología , Extractos Vegetales/química , Extractos Vegetales/toxicidad , ARN Viral/química , ARN Viral/metabolismo , Taxodium/metabolismo , Proteínas Virales/metabolismo , Internalización del Virus/efectos de los fármacos , Liberación del Virus/efectos de los fármacosRESUMEN
Nanoparticles can be effective drug delivery systems for treating bacterial and fungal infections in the skin. The nanoparticles used for drug therapy give many advantages over conventional formulations, such as increased solubility and storage stability, improved permeability and bioavailability, prolonged half-life, tissue targeting, and minimal side effects. In recent years, the concept of using nanoparticles to treat skin-microbiomerelated diseases has attracted increasing attention. This review article aimed to introduce recent progress using nanomedical strategies for drug delivery. Various modalities of nanocarriers can be used for antimicrobial therapy of disease, including liposomes, microemulsions, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and polymeric nanoparticles. This review systematically describes the structures and physicochemical properties of different nanocarriers, emphasizing antibacterial activity of nanoparticles for inhibiting infection. Nanoparticles for treating appendageal bacteria have gained attention in recent years, in particular, nanomedical approaches for managing acne. Issues related to the treatment of non-appendageal bacteria and fungi are also discussed. Finally, current obstacles to using nanocarriers for delivering medicines aimed at inhibiting infection and future developments are addressed.
Asunto(s)
Microbiota , Piel/microbiología , Animales , Dermatomicosis/tratamiento farmacológico , Humanos , Nanomedicina , Permeabilidad , Piel/anatomía & histología , Piel/metabolismo , Enfermedades Cutáneas Bacterianas/tratamiento farmacológicoRESUMEN
The bioactive components extracted from Scutellariae radix and Rhei rhizoma (SR) have been commonly used to treat liver diseases. The aim of this study was to verify the underlying mechanisms and antifibrotic effects of ethanol extract from the herbal combinatorial formula (SRE) in a dimethylnitrosamine (DMN)-administered rat model, with functional proteome tools. Our results indicated that the hepatic collagen content and alpha-smooth muscle actin expression were obviously alleviated by treatment with SRE. Comprehensive proteomics revealed global protein changes, and the network analysis implied that SRE application would attenuate oxidative stress and cytoskeleton dysregulation caused by DMN exposure. Next, marked downregulation of antioxidant enzymes mediated by DMN treatment was restored in the presence of SRE, while SRE treatment contributed to decreased MDA content. Moreover, protein carbonylation and DNA adduction induced by oxidative stress finally leading to liver injury were also reduced under SRE administration. These findings demonstrate that SRE could effectively prevent hepatic fibrosis mainly through regulating the redox status, and subsequently modulating the modification of intracellular molecules. Our experiments might help in developing novel therapeutic strategies against oxidation-caused liver diseases.