RESUMEN

BACKGROUND: Dysregulation of melanogenesis contributes to the development of skin hyperpigmentation diseases, which poses a treatment challenge. Following the establishment of CRTC3 screening methods to explore small molecules inhibiting melanogenesis for the topical treatment of hyperpigmentation diseases, we identified a candidate molecule, semaxanib. OBJECTIVE: To explore the antimelanogenic effects of semaxanib, a vascular endothelial growth factor receptor (VEGFR) 2 inhibitor, for potential applications in hyperpigmentation management and to unravel the role of VEGF signaling in melanocyte biology by investigating mechanism of action of semaxanib. METHODS: Mouse-derived spontaneously immortalized melanocytes, B16F10, and normal human primary epidermal melanocytes cells were treated with semaxanib, and cellular responses were assessed using cell viability assays and melanin content measurements. Molecular mechanisms were investigated using transcriptional activity assays, reverse-transcription polymerase chain reaction, and immunoblotting analysis. In vivo studies were conducted using an epidermis-humanized transgenic mouse model and ex vivo human skin tissues. RESULTS: Semaxanib ameliorated melanin content in cultured melanocytes by downregulating the expression of melanogenesis-associated genes by suppressing the CRTC3/microphthalmia-associated transcription factors. Topical application of semaxanib reduced melanin accumulation in the ultraviolet B-stimulated ex vivo human epidermis and tail of K14-stem cell factor transgenic mice. Mechanistically, the antimelanogenic effect induced by semaxanib was associated with SIK2-CRTC3-MITF rather than VEGF signaling in melanocytes. CONCLUSION: Semaxanib emerges as a promising candidate for the development of therapeutics for hyperpigmentation, potentially working independently of VEGF signaling in human melanocytes.

RESUMEN

α-Lactalbumin and ß-lactoglobulin are two major whey proteins that specifically bind immunoglobulin E and are suspected as major allergens causing cow's milk allergy (CMA). Recent studies have shown that thymic stromal lymphopoietin is a critical factor linking at the interface of the body and environment to the T-helper 2 response. However, it is not known whether thymic stromal lymphopoietin expression is changed by α-lactalbumin and ß-lactoglobulin in immune cells. Using RT-PCR and ELISA, the present study was conducted to examine if intravenous injection of α-lactalbumin and ß-lactoglobulin increased pro-inflammatory cytokines, T-helper 2 cytokines, and thymic stromal lymphopoietin expression in several immune cells, including macrophages, mast cells, and keratinocytes. Results showed that α-lactalbumin and ß-lactoglobulin induced thymic stromal lymphopoietin, interleukin-6, and tumor necrosis factor-α expression. It was concluded that the allergenicity of α-lactalbumin and ß-lactoglobulin may be attributed to thymic stromal lymphopoietin induction, T-helper 2 cytokines, and pro-inflammatory cytokines.

Asunto(s)

Citocinas/genética , Lactalbúmina/administración & dosificación , Lactoglobulinas/administración & dosificación , Alérgenos/inmunología , Animales , Bovinos , Línea Celular , Citocinas/análisis , Citocinas/sangre , Citocinas/inmunología , Citocinas/fisiología , Expresión Génica , Humanos , Interleucina-6/genética , Queratinocitos/metabolismo , Lactalbúmina/inmunología , Lactoglobulinas/inmunología , Macrófagos/metabolismo , Masculino , Mastocitos/metabolismo , Ratones , Ratones Endogámicos BALB C , FN-kappa B , Células RAW 264.7 , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/genética , Linfopoyetina del Estroma Tímico

RESUMEN

Printed circuit boards incorporated in most electrical and electronic equipment contain valuable metals such as Cu, Ni, Au, Ag, Pd, Fe, Sn, and Pb. In order to employ a hydrometallurgical route for the recycling of valuable metals from printed circuit boards, a mechanical pre-treatment step is needed. In this study, the metallic components from waste printed circuit boards have been enriched using a mechanical separation process. Waste printed circuit boards shredded to <10mm were milled using a stamp mill to liberate the various metallic components, and then the milled printed circuit boards were classified into fractions of <0.6, 0.6-1.2, 1.2-2.5, 2.5-5.0, and >5.0mm. The fractions of milled printed circuit boards of size <5.0mm were separated into a light fraction of mostly non-metallic components and a heavy fraction of the metallic components by gravity separation using a zig-zag classifier. The >5.0mm fraction and the heavy fraction were subjected to two-step magnetic separation. Through the first magnetic separation at 700 Gauss, 83% of the nickel and iron, based on the whole printed circuit boards, was recovered in the magnetic fraction, and 92% of the copper was recovered in the non-magnetic fraction. The cumulative recovery of nickel-iron concentrate was increased by a second magnetic separation at 3000 Gauss, but the grade of the concentrate decreased remarkably from 76% to 56%. The cumulative recovery of copper concentrate decreased, but the grade increased slightly from 71.6% to 75.4%. This study has demonstrated the feasibility of the mechanical separation process consisting of milling/size classification/gravity separation/two-step magnetic separation for enriching metallic components such as Cu, Ni, Al, and Fe from waste printed circuit boards.

Asunto(s)

Conservación de los Recursos Naturales , Electrónica , Residuos Industriales , Ensayo de Materiales , Fenómenos Mecánicos , Metales/química , Eliminación de Residuos , Magnetismo , Tamaño de la Partícula

RESUMEN

In view of the increasing importance of the waste processing and recycling to meet the strict environmental regulations, the present investigation reports an adsorption process using the cationic exchanger Amberlite IR 120 for the recovery/removal of copper from the synthetic sulphate solution containing copper

Asunto(s)

Cobre/aislamiento & purificación , Poliestirenos , Sulfatos , Contaminantes Químicos del Agua/aislamiento & purificación , Adsorción , Conservación de los Recursos Naturales , Soluciones , Purificación del Agua/métodos