RESUMEN
Hyperpigmentation is a common condition that causes darker spots or patches on the skin, which often look brown, black, gray, red, or pink. This results in unresolved psychological impact due to high anxiety, depression, and somatoform disorder. We aimed to repurpose an antidiabetic drug, miglitol, as an effective compound against hyperpigmentation when applied as a cosmeceutical agent. The present study investigated the antimelanogenic effects of miglitol and the trehalase inhibitor validamycin A. Miglitol in isolation exhibited no cytotoxicity and significantly reduced the melanin production and intracellular tyrosinase activity in B16F10 melanoma cells. The Western blotting results showed that miglitol reduces the expression of melanogenic regulatory factors, including tyrosinase, tyrosinase-related protein (TRP)-1, TRP-2, and microphthalmia-associated transcription factor (MITF). Mechanistically, miglitol appears to suppress melanin synthesis through cAMP-dependent protein kinase (PKA)-dependent downregulation of MITF, a master transcription factor in melanogenesis. The antimelanogenic effects of miglitol was mediated by downregulation of the p38 signaling pathway and upregulation of extracellular signal-regulated kinase (ERK). Moreover, miglitol decreases P-GSK3ß and ß-catenin levels compared to those in the untreated group. However, miglitol activated P-ß-catenin expression compared to that in the untreated group. Finally, we tested the potential of miglitol in topical application through primary human skin irritation tests on the normal skin (upper back) of 33 volunteers. In these assays, miglitol (125 and 250 µM) did not induce any adverse reactions. Taken together, these findings suggest that the regulation of melanogenesis by miglitol may be mediated by the PKA, MAPK, and GSK3ß/ß-Catenin signaling pathways and that miglitol might provide new insights into drug repurposing for the treatment of hyperpigmentation symptoms.
Asunto(s)
Hiperpigmentación , Melanoma Experimental , Melanoma , Animales , Humanos , beta Catenina/metabolismo , Línea Celular Tumoral , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Melaninas , Melanoma/tratamiento farmacológico , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/metabolismo , Monofenol Monooxigenasa/metabolismo , Transducción de Señal , Ratones , Proteínas Quinasas Activadas por MitógenosRESUMEN
PURPOSE: This study was done to compare breast feeding rates and factors influencing feeding practice between late preterm (34 ≤ GA < 37) and preterm infants (GA<34). METHODS: A survey was done of 207 late preterm and 117 preterm infants in neonatal intensive care units (NICU) of 4 university hospitals in D city. Data were collected from July 2009 to June 2010 from 324 medical records in the NICU. Breast-feeding at home was checked either by telephone survey or questioning during hospital visits. RESULTS: Rate of breast feeding for late preterm infants was significantly lower than for preterm infants. There was no significant difference in breast-feeding at home. We found differences in factors influencing breast feeding between the two groups. Factors influencing feeding for late preterm infants were type of delivery, mothers' occupation, feeding type during hospitalization, time elapse from hospital discharge, total admission days, infant's body weight at first feeding and length of NPO (nothing by mouth). Factors influencing feeding for preterm infants were birth order, maternal disease and obstetric complications, and one-minute Apgar score. CONCLUSION: Results of the study show low rates of breast-feeding for late preterm infants indicating a need for breast-feeding education for mothers of these infants.