RESUMEN
Exposure through arsenic-contaminated air and food caused by the burning of coal is a major environmental public health concern in Guizhou Province of China. Previous studies have shown that immunological dysfunction is involved in the pathogenesis and carcinogenesis of arsenic; however, knowledge regarding effective prevention measures have not been fully examined. The effect of Ginkgo biloba extract (EGb761) on arsenic-induced skin damage of human immortalized keratinocyte cells (HaCaT) was first evaluated in this study. The results showed that 200 µg/mL EGb761 can reduce the expression of miR-155-5p, and the indicators reflecting arsenic-induced skin damage (Krt1, Krt6c and Krt10) in arsenic-exposed cells (P < 0.05), the expression levels of NF-AT1; the indicators reflecting arsenic-induced immunological dysfunction (IL-2, IFN-γ) in cells; and the levels of secreted IL-2 and IFN-γ in cell supernatants were significantly increased (P < 0.05). Further randomized controlled double-blind experiments showed that compared to the placebo control group, the expression level of miR-155-5p in the plasma of the Ginkgo biloba intervention group, the indicators in the serum reflecting arsenic-induced skin damage (Krt1, Krt6c, and Krt10) and the epithelial-mesenchymal transformation (EMT) vimentin were significantly reduced (P < 0.05), but the levels of NF-AT1 and the indicators reflecting arsenic-induced immunological dysfunction (IL-2, IFN-γ) and EMT (E-cadherin) in serum were significantly increased (P < 0.05). Our study provides some limited evidence that Ginkgo biloba L. can increase the expression of NF-AT1 by downregulating the level of miR-155-5p, alleviating immunological dysfunction, and decreasing the expression of EMT biomarkers, thus indirectly improving arsenic-induced skin damage.
Asunto(s)
Intoxicación por Arsénico/tratamiento farmacológico , Queratinocitos/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Enfermedades de la Piel/tratamiento farmacológico , Adulto , Anciano , Intoxicación por Arsénico/sangre , Intoxicación por Arsénico/complicaciones , Intoxicación por Arsénico/genética , Línea Celular , Proliferación Celular/efectos de los fármacos , Método Doble Ciego , Femenino , Ginkgo biloba , Humanos , Interferón gamma/sangre , Interferón gamma/genética , Interleucina-2/sangre , Interleucina-2/genética , Queratinocitos/metabolismo , Masculino , MicroARNs/sangre , Persona de Mediana Edad , Factores de Transcripción NFATC/sangre , Factores de Transcripción NFATC/genética , Factores de Transcripción NFATC/metabolismo , Enfermedades de la Piel/sangre , Enfermedades de la Piel/inducido químicamente , Enfermedades de la Piel/genéticaRESUMEN
In light of Medical Hydrology, thermal waters (TW) are all-natural mineral waters that emerge inside a thermal resort and have therapeutic applications. Their beneficial effect has been empirically recognized for centuries, being indicated for symptom alleviation and/or treatment of several diseases, almost all associated with inflammation. Indeed, an anti-inflammatory effect has been attributed to many different Portuguese TW but there is no scientific validation supporting this empiric knowledge. In the present study, we aimed to investigate the anti-inflammatory properties of 14 TW pertaining to thermal centers located in the Central Region of Portugal, and grouped according to their ionic profile. Mouse macrophage cells stimulated with lipopolysaccharide (LPS), a Toll-like receptor 4 agonist, were exposed to culture medium prepared in TW. Metabolism, nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression levels and the scavenging capacity of TW, were investigated in vitro. 11 out of 14 TW reduced NO production and/or iNOS expression, and/or scavenging activity, in macrophages exposed to LPS. The sulphated/calcic TW did not show any effect on at least one of the inflammatory parameters evaluated. Two sulphurous/bicarbonate/sodic TW and the sulphurous/chlorinated/sodic TW promoted an increase in NO production and/or iNOS expression. Our results validate, for the first time, the anti-inflammatory properties of Portuguese TW, supporting their therapeutic use in the treatment of inflammation-related diseases and promoting their putative application in cosmetic products and medical devices.
Asunto(s)
Antiinflamatorios/farmacología , Agua Subterránea/química , Calor/uso terapéutico , Inflamación/tratamiento farmacológico , Enfermedades de la Piel/tratamiento farmacológico , Animales , Antiinflamatorios/química , Línea Celular , Depuradores de Radicales Libres/metabolismo , Expresión Génica/efectos de los fármacos , Humanos , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/patología , Lipopolisacáridos/toxicidad , Macrófagos/efectos de los fármacos , Ratones , Óxido Nítrico/genética , Óxido Nítrico Sintasa de Tipo II/genética , Portugal , Enfermedades de la Piel/genética , Enfermedades de la Piel/patologíaRESUMEN
Skin toxicities induced by epidermal growth factor receptor inhibitors such as Erlotinib plagues clinical challenges. Chinese formulas have a unique advantage in reducing side effects. Here, we aim to investigate the skin protecting function of XiaoZhenFang (XZF), a clinical adjuvant prescription made up of Lonicerae Japonicae Flos, Lithospermum Erythrorhizon, Smilacis Glabrae Rhizoma, Forsythiae Fructus, Spirodelae Herba, Cortex Moutan and Prunellae Spica. Our data showed that XZF aqueous extract effectively reduced skin toxicities induced by Erlotinib in vivo using established mice model. Next, we used a systems pharmacology approach to investigate the pharmacological mechanism of XZF with the goal of understanding its effects at the system, organ, and molecular levels. 44 candidate compounds and 103 potential targets were identified by network pharmacology. Inflammation, cell stress and the EGFR-related signal pathways, which may participate in the skin protection afforded by XZF, were analyzed by gene enrichment. Importantly, our in vivo experimental results largely validated XZF's mechanism of action, as predicted by the system pharmacology analysis. Our study uncovered the effect and mechanism of XZF in attenuating skin toxicities induced by EGFRI, providing a basis for the development of in-hospital preparations and new drugs for the prevention of skin toxicities.
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Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Receptores ErbB/antagonistas & inhibidores , Clorhidrato de Erlotinib/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos , Enfermedades de la Piel/metabolismo , Animales , Femenino , Ratones , Ratones Endogámicos BALB C , Transducción de Señal/efectos de los fármacos , Piel/efectos de los fármacos , Piel/patología , Enfermedades de la Piel/inducido químicamente , Enfermedades de la Piel/genética , Enfermedades de la Piel/patologíaAsunto(s)
Quiste Epidérmico/patología , Síndromes Neoplásicos Hereditarios/diagnóstico , Enfermedades de la Piel/patología , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/terapia , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Apendicectomía , Neoplasias del Apéndice/diagnóstico , Neoplasias del Apéndice/genética , Neoplasias del Apéndice/terapia , Enfermedades Asintomáticas , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/genética , Tumor Carcinoide/terapia , Quimioterapia Adyuvante , Terapia Combinada , Diagnóstico Diferencial , Endoscopía del Sistema Digestivo , Quiste Epidérmico/genética , Quiste Epidérmico/cirugía , Fluorouracilo/administración & dosificación , Síndrome de Gardner/diagnóstico , Síndrome de Gardner/genética , Cabeza , Hepatectomía , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Masculino , Terapia Neoadyuvante , Síndromes Neoplásicos Hereditarios/patología , Oxaliplatino/administración & dosificación , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/genética , Neoplasias del Recto/cirugía , Enfermedades de la Piel/genética , Enfermedades de la Piel/cirugíaRESUMEN
Excessive alternative macrophage activation contributes to fibrosis. We studied the effects of nortrachelogenin, the major lignan component of Pinus sylvestris knot extract, on alternative (M2) macrophage activation. J774 murine and THP-1 human macrophages were cultured with IL-4+IL-13 to induce alternative activation, together with the extract and its components. Effects of nortrachelogenin were also studied in bleomycin-induced murine dermal fibrosis model. Knot extract significantly decreased the expression of alternative activation markers-arginase 1 in murine macrophages (97.4 ± 1.3% inhibition at 30 µg/mL) and CCL13 and PDGF in human macrophages-as did nortrachelogenin (94.9 ± 2.4% inhibition of arginase 1 at 10 µM). Nortrachelogenin also decreased PPARγ expression but had no effect on STAT6 phosphorylation. In vivo, nortrachelogenin reduced bleomycin-induced increase in skin thickness as well as the expression of collagens COL1A1, COL1A2, and COL3A1 (all by >50%). In conclusion, nortrachelogenin suppressed IL-4+IL-13-induced alternative macrophage activation and ameliorated bleomycin-induced fibrosis, indicating therapeutic potential in fibrosing conditions.
Asunto(s)
Bleomicina/efectos adversos , Furanos/administración & dosificación , Interleucina-13/inmunología , Interleucina-4/inmunología , Lignanos/administración & dosificación , Activación de Macrófagos/efectos de los fármacos , Pinus sylvestris/química , Extractos Vegetales/administración & dosificación , Enfermedades de la Piel/tratamiento farmacológico , Animales , Colágeno/inmunología , Fibrosis/inducido químicamente , Fibrosis/tratamiento farmacológico , Fibrosis/etiología , Fibrosis/inmunología , Humanos , Interleucina-13/genética , Interleucina-4/genética , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedades de la Piel/inducido químicamente , Enfermedades de la Piel/genética , Enfermedades de la Piel/inmunologíaRESUMEN
The characteristics of tongue coating are very important symbols for disease diagnosis in traditional Chinese medicine (TCM) theory. As a habitat of oral microbiota, bacteria on the tongue dorsum have been proved to be the cause of many oral diseases. The high-throughput next-generation sequencing (NGS) platforms have been widely applied in the analysis of bacterial 16S rRNA gene. We developed a methodology based on genus-specific multiprimer amplification and ligation-based sequencing for microbiota analysis. In order to validate the efficiency of the approach, we thoroughly analyzed six tongue coating samples from lung cancer patients with different TCM types, and more than 600 genera of bacteria were detected by this platform. The results showed that ligation-based parallel sequencing combined with enzyme digestion and multiamplification could expand the effective length of sequencing reads and could be applied in the microbiota analysis.
Asunto(s)
Bacterias/genética , ARN Ribosómico 16S/genética , Enfermedades de la Piel/microbiología , Lengua/microbiología , Adulto , Anciano , Bacterias/clasificación , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Piel/genéticaAsunto(s)
Antirreumáticos/efectos adversos , Terapia Biológica/efectos adversos , Predisposición Genética a la Enfermedad , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades de la Piel/inducido químicamente , Enfermedades de la Piel/genética , Adulto , Antirreumáticos/uso terapéutico , Proteínas Ricas en Prolina del Estrato Córneo/genética , Femenino , Marcadores Genéticos , Antígenos HLA/genética , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Enfermedades Reumáticas/genéticaRESUMEN
BACKGROUND: Dermatoporosis is an emerging clinical condition caused by chronological skin aging, long-term sun exposure and chronic use of corticosteroids; however, genomic expression in dermatoporosis and the efficacy of different therapeutic approaches to prevent and treat dermatoporosis have not been investigated so far. OBJECTIVE: We examined the possible effect of topical retinaldehyde (RAL) and defined-size hyaluronate fragments (HAFi) on the expression of hyalurosome genes potentially involved in the pathogenesis of dermatoporosis. We also explored the effect of different concentrations of HAFi on skin thickness. METHODS: 13 persons were separated into a young control group (n = 8) and a dermatoporosis group (n = 5). Topical treatment of both groups with a combination of 0.05% RAL and 1 or 0.2% HAFi was applied on the forearm twice daily for 30 days. Forearm skin biopsies of both groups were performed before and after application. Hyalurosome genes CD44, heparin-binding epidermal growth factor (HB-EGF), ErbB1, hyaluronate synthase 3 (HAS3) and Hyal2 were chosen as potential markers of dermatoporosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed for quantification of mRNA expression of the target hyalurosome genes. Measurement of forearm skin thickness before and after treatment was performed by ultrasonography. Analysis of the results was done by Student's t test. A p value <0.05 was considered statistically significant. RESULTS: In qRT-PCR analysis the relative expression of hyalurosome (CD44, HAS3, HB-EGF) genes was found to be reduced in patients prior to topical treatment and to be notably increased following treatment. The reduced expression of CD44 and HAS3 in patients was specifically restored in dermatoporotic patients after treatment. No difference in skin thickness was observed in controls after treatment. The treatment caused a significant increase in skin thickness in dermatoporotic patients. This increase was more significant with 1% HAFi when compared to 0.2% HAFi. RAL and HAFi also caused a significant reduction in purpuric lesions in patients with dermatoporosis. CONCLUSION: Our results indicate that topically applied RAL and HAFi regulate hyalurosome gene expression in dermatoporosis and that they show a dose-dependent effect on the correction of skin atrophy in dermatoporotic patients.
Asunto(s)
Moléculas de Adhesión Celular/genética , Regulación de la Expresión Génica , Factor de Crecimiento Similar a EGF de Unión a Heparina/genética , Receptores de Hialuranos/genética , Ácido Hialurónico/administración & dosificación , Hialuronoglucosaminidasa/genética , Retinaldehído/administración & dosificación , Enfermedades de la Piel/genética , Adyuvantes Inmunológicos/administración & dosificación , Administración Tópica , Atrofia/diagnóstico por imagen , Atrofia/patología , Biopsia , Moléculas de Adhesión Celular/biosíntesis , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Estudios de Seguimiento , Antebrazo , Factor de Crecimiento Similar a EGF de Unión a Heparina/biosíntesis , Humanos , Receptores de Hialuranos/biosíntesis , Hialuronoglucosaminidasa/biosíntesis , Queratinocitos/metabolismo , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Retrospectivos , Piel/diagnóstico por imagen , Piel/patología , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/metabolismo , Factores de Tiempo , Resultado del Tratamiento , UltrasonografíaRESUMEN
During the past years, significant progress in the understanding of the complexity, regulation, and relevance of innate immune responses underlying several inflammatory conditions with neutrophilic skin involvement has been made. These diseases belong to the novel class of autoinflammatory diseases, and several are caused by mutations in genes regulating the function of innate immune complexes, termed inflammasomes, leading to enhanced secretion of the proinflammatory cytokine IL-1ß. Consequently, targeting of IL-1ß has proven successful in the treatment of these diseases, and the identification of related pathogenic mechanisms in other more common skin diseases characterized by autoinflammation and neutrophilic tissue damage also provides extended opportunities for therapy by interfering with IL-1 signaling.
Asunto(s)
Enfermedades Autoinmunes/inmunología , Terapia Biológica , Inflamasomas/inmunología , Queratinocitos/inmunología , Enfermedades de la Piel/inmunología , Acné Vulgar/genética , Acné Vulgar/inmunología , Acné Vulgar/terapia , Síndrome de Hiperostosis Adquirido/genética , Síndrome de Hiperostosis Adquirido/inmunología , Síndrome de Hiperostosis Adquirido/terapia , Animales , Artritis Infecciosa/genética , Artritis Infecciosa/inmunología , Artritis Infecciosa/terapia , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/terapia , Humanos , Inflamasomas/genética , Ratones , Piodermia Gangrenosa/genética , Piodermia Gangrenosa/inmunología , Piodermia Gangrenosa/terapia , Síndrome de Schnitzler/genética , Síndrome de Schnitzler/inmunología , Síndrome de Schnitzler/terapia , Enfermedades de la Piel/genética , Enfermedades de la Piel/terapiaRESUMEN
Nuclear factor-κB (NF-κB) regulates cellular responses to inflammation and aging, and alterations in NF-κB signaling underlie the pathogenesis of multiple human diseases. Effective clinical therapeutics targeting this pathway remain unavailable. In primary human keratinocytes, we found that hypochlorite (HOCl) reversibly inhibited the expression of CCL2 and SOD2, two NF-κB-dependent genes. In cultured cells, HOCl inhibited the activity of inhibitor of NF-κB kinase (IKK), a key regulator of NF-κB activation, by oxidizing cysteine residues Cys114 and Cys115. In NF-κB reporter mice, topical HOCl reduced LPS-induced NF-κB signaling in skin. We further evaluated topical HOCl use in two mouse models of NF-κB-driven epidermal disease. For mice with acute radiation dermatitis, topical HOCl inhibited the expression of NF-κB-dependent genes, decreased disease severity, and prevented skin ulceration. In aged mice, topical HOCl attenuated age-dependent production of p16INK4a and expression of the DNA repair gene Rad50. Additionally, skin of aged HOCl-treated mice acquired enhanced epidermal thickness and proliferation, comparable to skin in juvenile animals. These data suggest that topical HOCl reduces NF-κB-mediated epidermal pathology in radiation dermatitis and skin aging through IKK modulation and motivate the exploration of HOCl use for clinical aims.
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Regulación de la Expresión Génica/efectos de los fármacos , Ácido Hipocloroso/uso terapéutico , FN-kappa B/fisiología , Oxidantes/uso terapéutico , Envejecimiento de la Piel/efectos de los fármacos , Enfermedades de la Piel/tratamiento farmacológico , Transportadoras de Casetes de Unión a ATP/biosíntesis , Transportadoras de Casetes de Unión a ATP/genética , Ácido Anhídrido Hidrolasas , Administración Cutánea , Sustitución de Aminoácidos , Animales , Células Cultivadas , Quimiocina CCL2/biosíntesis , Quimiocina CCL2/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/biosíntesis , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Cisteína/efectos de los fármacos , Reparación del ADN/efectos de los fármacos , Proteínas de Unión al ADN , Evaluación Preclínica de Medicamentos , Femenino , Genes Reporteros , Humanos , Ácido Hipocloroso/administración & dosificación , Quinasa I-kappa B/antagonistas & inhibidores , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , FN-kappa B/genética , Oxidantes/administración & dosificación , Oxidación-Reducción , Radiodermatitis/tratamiento farmacológico , Radiodermatitis/patología , Enfermedades de la Piel/genética , Enfermedades de la Piel/metabolismo , Enfermedades de la Piel/patología , Úlcera Cutánea/prevención & control , Superóxido Dismutasa/biosíntesis , Superóxido Dismutasa/genética , Transcripción Genética/efectos de los fármacos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Resonance Raman spectroscopy (RRS) is a non-invasive method that has been developed to assess carotenoid status in human tissues including human skin in vivo. Skin carotenoid status has been suggested as a promising biomarker for human studies. This manuscript describes research done relevant to the development of this biomarker, including its reproducibility, validity, feasibility for use in field settings, and factors that affect the biomarker such as diet, smoking, and adiposity. Recent studies have evaluated the response of the biomarker to controlled carotenoid interventions, both supplement-based and dietary [e.g., provision of a high-carotenoid fruit and vegetable (F/V)-enriched diet], demonstrating consistent response to intervention. The totality of evidence supports the use of skin carotenoid status as an objective biomarker of F/V intake, although in the cross-sectional setting, diet explains only some of the variation in this biomarker. However, this limitation is also a strength in that skin carotenoids may effectively serve as an integrated biomarker of health, with higher status reflecting greater F/V intake, lack of smoking, and lack of adiposity. Thus, this biomarker holds promise as both a health biomarker and an objective indicator of F/V intake, supporting its further development and utilization for medical and public health purposes.
Asunto(s)
Carotenoides/metabolismo , Enfermedades de la Piel/metabolismo , Espectrometría Raman/métodos , Envejecimiento/genética , Envejecimiento/metabolismo , Envejecimiento/fisiología , Biomarcadores/química , Biomarcadores/metabolismo , Carotenoides/genética , Carotenoides/fisiología , Dietoterapia/tendencias , Estudios de Factibilidad , Humanos , Dispersión de Radiación , Enfermedades de la Piel/genética , Enfermedades de la Piel/fisiopatologíaRESUMEN
Plate-like osteoma cutis is a rare disorder that has been historically classified as a congenital syndrome. It has a possible relationship to a mutation in the gene (GNAS1) that encodes the α-subunit of the stimulatory G protein, which regulates adenyl cyclase activity. We report a case of extensive plaque-like masses on the scalp and face with no abnormalities in calcium or phosphate metabolism and no preceding inflammatory cutaneous conditions. With less than ten reported cases, to our knowledge, this is one the few cases of acquired plate-like osteoma cutis described in the literature.
Asunto(s)
Osificación Heterotópica/patología , Osteoma/patología , Enfermedades de la Piel/patología , Calcio/metabolismo , Cromograninas , Dermatosis Facial/diagnóstico , Dermatosis Facial/patología , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Humanos , Masculino , Persona de Mediana Edad , Osificación Heterotópica/diagnóstico , Osificación Heterotópica/genética , Osificación Heterotópica/terapia , Osteoma/genética , Osteoma/terapia , Fósforo/metabolismo , Dermatosis del Cuero Cabelludo/diagnóstico , Dermatosis del Cuero Cabelludo/patología , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/genética , Enfermedades de la Piel/terapia , Muslo , TóraxRESUMEN
Lipid storage myopathy (LSM) is pathologically characterized by prominent lipid accumulation in muscle fibers due to lipid dysmetabolism. Although extensive molecular studies have been performed, there are only four types of genetically diagnosable LSMs: primary carnitine deficiency (PCD), multiple acyl-coenzyme A dehydrogenase deficiency (MADD), neutral lipid storage disease with ichthyosis, and neutral lipid storage disease with myopathy. Making an accurate diagnosis, by specific laboratory tests including genetic analyses, is important for LSM as some of the patients are treatable: individuals with PCD show dramatic improvement with high-dose oral L-carnitine supplementation and increasing evidence indicates that MADD due to ETFDH mutations is riboflavin responsive.
Asunto(s)
Metabolismo de los Lípidos , Músculo Esquelético/patología , Acil-CoA Deshidrogenasa/deficiencia , Acil-CoA Deshidrogenasa/genética , Carnitina/deficiencia , Carnitina/genética , Diagnóstico Diferencial , Humanos , Eritrodermia Ictiosiforme Congénita/genética , Eritrodermia Ictiosiforme Congénita/patología , Eritrodermia Ictiosiforme Congénita/fisiopatología , Eritrodermia Ictiosiforme Congénita/terapia , Errores Innatos del Metabolismo Lipídico/genética , Errores Innatos del Metabolismo Lipídico/patología , Errores Innatos del Metabolismo Lipídico/fisiopatología , Errores Innatos del Metabolismo Lipídico/terapia , Músculo Esquelético/fisiopatología , Enfermedades Musculares/genética , Enfermedades Musculares/patología , Enfermedades Musculares/fisiopatología , Enfermedades Musculares/terapia , Enfermedades de la Piel/enzimología , Enfermedades de la Piel/genética , Enfermedades de la Piel/patología , Enfermedades de la Piel/fisiopatologíaRESUMEN
In autosomal dominant skin disorders, a superimposed mosaic involvement arranged in a linear or otherwise segmental pattern is sometimes noted. Molecular proof of such "type 2 segmental manifestation" has so far been provided in Hailey-Hailey disease and Cowden syndrome. A similar superimposed segmental involvement can be found in numerous common disorders with a polygenic background, such a psoriasis, lichen planus, or vitiligo. In polygenic diseases, however, we can never recognize with certainty a "type 1 segmental manifestation", which is why we should use more neutral terms in the form of "isolated" versus "superimposed" segmental involvement. In the near future, the new paradigm of superimposed segmental manifestation may hopefully help elucidate the molecular basis of both monogenic and polygenic skin disorders (AU)
En los trastornos cutáneos autosómicos dominantes a veces se aprecia un mosaicismo sobreimpuesto con una disposición en patrón lineal o segmentario. La prueba molecular de ese tipo de «manifestación segmentaria tipo 2» la han proporcionado la enfermedad de Hailey-Hailey y el síndrome de Cowden. En numerosos trastornos frecuentes con una herencia poligénica como la psoriasis, el liquen plano o el vitíligo, se puede encontrar una afectación segmentaria sobreimpuesta similar. Sin embargo, en las enfermedades poligénicas nunca podemos reconocer con certeza una «manifestación segmentaria tipo 1», por 10 que utilizamos términos más neutrales, como afectación segmentaria «aislada» frente a «sobreimpuesta». En un futuro próximo el nuevo paradigma de manifestación segmentaria sobreimpuesta ayudará, en el mejor de los casos, a esclarecer la base molecular de los trastornos cutáneos monogénicos y poligénicos (AU)
Asunto(s)
Humanos , Enfermedades de la Piel/genética , Enfermedades Raras/genética , Duplicaciones Segmentarias en el Genoma/genética , Pénfigo Familiar Benigno/genética , Trastornos de los Cromosomas/genética , Leiomiomatosis/genética , Recombinación GenéticaRESUMEN
UV irradiation results in DNA damage, inflammation and immunosuppression, leading to the development of basal and squamous cell carcinomas. Earlier data show that topical treatment with nondenatured soy extracts reduced the incidence and delayed the development/progression of already-initiated skin tumors in high-risk hairless mice. Here we show that pretreatment with nondenatured soy extracts reduced UVB-induced Thymine-Thymine (TT) dimer formation. In vitro, nondenatured soy extracts enhanced UVB-induced checkpoint kinase-1 (Chk1) activation, suggesting a delay in cell cycle progression that enables longer time for DNA repair. Soy also reduced UVB-induced cyclo-oxygenase-2 (COX-2) expression and prostaglandin E2 secretion, and inhibited p38 MAP kinase activation, suggesting its anti-inflammatory activity. Mice pretreated topically with nondenatured soy extracts had reduced levels of UVB-induced TT dimers and COX-2 expression in their skins compared to UVB alone. The nondenatured soy extracts also inhibited vascular endothelial growth factor-induced endothelial tube formation in Matrigel, suggesting a possible inhibitory effect on angiogenesis and tumor progression. Taken together, nondenatured soy extracts could prevent or reduce UVB-induced skin damage via multiple mechanisms, affecting both the initiation and the progression of skin cancer. These data suggest that topical application of nondenatured soy extracts could potentially reduce the incidence of skin cancer.
Asunto(s)
Glycine max/química , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Enfermedades de la Piel/tratamiento farmacológico , Piel/efectos de la radiación , Rayos Ultravioleta , Animales , Línea Celular , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1) , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Daño del ADN , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Humanos , Inflamación/tratamiento farmacológico , Inflamación/patología , Ratones , Proteínas Quinasas/metabolismo , Piel/metabolismo , Enfermedades de la Piel/genética , Enfermedades de la Piel/metabolismo , Enfermedades de la Piel/patología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
INTRODUCTION: Polychlorinated biphenyls (PCBs) and dibenzofurans (PCDFs) are ubiquitous persistent pollutants in humans. Whether people with different genotypes are with different susceptibility to these chemicals are unknown. In a group of people highly exposed to PCBs/PCDFs, we tested the hypothesis that genotypic polymorphisms affected susceptibility for development of skin manifestations. METHODS: In 1979, approximately 2000 people in central Taiwan ingested cooking oil contaminated with PCBs/PCDFs. Skin disorder such as chloracne, abnormal nail, hyperkeratosis and skin allergy were found in PCBs/PCDFs exposed group. We recruited exposed and community background exposure subjects for blood testing and telephone-interview. Single nucleotide polymorphisms, AhR Arg554Lys, CYP1A1 Ile462Val, CYP1A1 T6235C, and GSTM1/T1 deletion, were determined. Occurrence of skin manifestations was compared among people with different genotypes while stratified by PCB exposure levels by logistic regression. RESULTS: Data on exposure, medical history, and genotypes were obtained from 393 exposed and 181 background exposure groups. Skin manifestations including chloracne, allergy, abnormal nail, and hyperkeratosis were more prevalent in exposed people in a dose-related manner. Among highly exposed individuals, combined CYP1A1-MspI mutant genotype and GSTM1-null genotype were associated with increased risk of chloracne (odds ratio 2.8, 95% confidence interval 1.1-7.6). Among intermediately exposed individuals, GSTM1 null genotype was associated with skin allergy. AhR Arg554Lys genotype and GSTT1 null genotype were not related to susceptibility to skin manifestations in PCB/PCDF-exposed population. CONCLUSION: CYP1A1 and GSTM1 genotypic polymorphisms might be related to the susceptibility to PCB/PCDF-induced skin manifestations.
Asunto(s)
Benzofuranos/toxicidad , Citocromo P-450 CYP1A1/genética , Predisposición Genética a la Enfermedad , Glutatión Transferasa/genética , Bifenilos Policlorados/toxicidad , Enfermedades de la Piel/genética , Adulto , Dibenzofuranos Policlorados , Exposición a Riesgos Ambientales , Contaminantes Ambientales/toxicidad , Femenino , Contaminación de Alimentos , Humanos , Masculino , Persona de Mediana Edad , Aceites de Plantas , Polimorfismo Genético , Enfermedades de la Piel/inducido químicamente , Taiwán/epidemiologíaRESUMEN
The effect of French maritime pine bark extract (PBE) on the gene expression profile of HaCaT human keratinocytes was studied using high density filter arrays. The expression profile of both control and PBE-treated cells was determined. Interestingly, PBE was shown to downregulate both calgranulin A and B genes which are known to be upregulated in psoriasis and various dermatoses. Thus, PBE could be considered in human dermatoses.