The purpose of this study is to identify amino acid derivatives with potent anti-eumelanogenic activity. First, we compared the effects of twenty different amidated amino acids on tyrosinase (TYR)-mediated dopachrome formation in vitro and melanin content in dark-pigmented human melanoma MNT-1 cells. The results showed that only L-cysteinamide inhibited TYR-mediated dopachrome formation in vitro and reduced the melanin content of cells. Next, the antimelanogenic effect of L-cysteinamide was compared to those of other thiol compounds (L-cysteine, N-acetyl L-cysteine, glutathione, L-cysteine ethyl ester, N-acetyl L-cysteinamide, and cysteamine) and positive controls with known antimelanogenic effects (kojic acid and β-arbutin). The results showed the unique properties of L-cysteinamide, which effectively reduces melanin content without causing cytotoxicity. L-Cysteinamide did not affect the mRNA and protein levels of TYR, tyrosinase-related protein 1, and dopachrome tautomerase in MNT-1 cells. L-Cysteinamide exhibited similar properties in normal human epidermal melanocytes (HEMs). Experiments using mushroom TYR suggest that L-cysteinamide at certain concentrations can inhibit eumelanin synthesis through a dual mechanism by inhibiting TYR-catalyzed dopaquinone synthesis and by diverting the synthesized dopaquinone to the formation of DOPA-cysteinamide conjugates rather than dopachrome. Finally, L-cysteinamide was shown to increase pheomelanin content while decreasing eumelanin and total melanin contents in MNT-1 cells. This study suggests that L-cysteinamide has an optimal structure that can effectively and safely inhibit eumelanin synthesis in MNT-1 cells and HEMs, and will be useful in controlling skin hyperpigmentation.

Background: Most patients with chronic kidney disease develop variable degrees of secondary hyperparathyroidism, which is resolved after kidney transplantation (KT). However, persistent hyperparathyroidism after KT in adults is reported to occur in 50% patients undergoing KT; this has not been investigated thoroughly in children. Here, we analyzed the prevalence of hyperparathyroidism after KT and its risk factors among children in a single-referral hospital. Methods: This retrospective observational study analyzed medical records of children who underwent KT between 2007 and 2020. Persistent hyperparathyroidism was defined as the median PTH level of more than 65 pg/mL; its annual prevalence, risk factors, treatment status, and association with graft outcome, were analyzed. Results: Among 153 patients, 56% were boys and their mean age was 10.5 years. The prevalence of persistent hyperparathyroidism was about 36% after 1 year, which remained stable up to 4 years after KT. The occurrence of persistent hyperparathyroidism was associated with longer pretransplant dialysis duration and hyperphosphatemia. Of the enrolled children, one underwent parathyroidectomy and 15 received cinacalcet therapy. A total of 49.6% children either had a graft failure or their eGFR was less than 60ml/min/1.732 after a median of 4.6 years of KT; hyperparathyroidism status was associated with decreased kidney function. Conclusion: Prevalence of persistent hyperparathyroidism after KT is common in children, with a considerable portion of them being treated medically or surgically. The degree of secondary hyperparathyroidism before KT may be a risk factor for development of persistent hyperparathyroidism, which has been associated with decreased graft function.