Effectiveness and safety of tofacitinib combined with narrowband ultraviolet B phototherapy for patients with refractory vitiligo in real-world clinical practice.

Vitiligo is a chronic treatment-resistant autoimmune disorder characterized by circumscribed depigmented maculae. This study was conducted to evaluate the efficacy and safety of tofacitinib combined with narrowband ultraviolet B (NB-UVB) phototherapy for refractory nonsegmental vitiligo. Fifteen patients with nonsegmental vitiligo resistant to conventional therapies were administered oral tofacitinib at 5 mg twice daily plus topical halometasone cream, tacrolimus 0.1% ointment, or pimecrolimus cream twice daily and NB-UVB three times per week for 16 weeks. The control group comprised 19 patients with nonsegmental vitiligo treated with topical drugs plus NB-UVB same as the combination group. Treatment efficacy was measured by the percentage of repigmentation of vitiligo lesions at 4th, 8th, 12th, and 16th week after beginning treatment. From 8th week, the repigmentation level was significantly higher in the combination group than in the controls. From fourth week, the response rate was significantly higher in the combination group than in the controls. Only one patient in the combination group reported mild pain in the hand and foot joints, but the pain subsided with cessation of therapy. No other severe adverse effects occurred. So, tofacitinib in combination with NB-UVB phototherapy may be an effective and safe alternative modality for refractory vitiligo.

Systems toxicology used in nanotoxicology: mechanistic insights into the hepatotoxicity of nano-copper particles from toxicogenomics.

In some studies, nano-copper particles have been found to be acutely toxic to exposed mice, with the liver and kidney being the target tissues. However, the characteristics of subacute toxicity from repeated nano-copper exposure in rats and the molecular mechanism of its hepatotoxicity at the genomic level remain unclear. We investigated the mechanisms of nano-copper-induced hepatotoxicity, which were identified from hepatic gene expression profiles that were phenotypically anchored to conventional toxicological outcomes, and identified biomarkers of nanotoxicity caused by nano-copper. Male Wistar rats were administered nano-copper or micro-copper at different doses for five days. Subsequently, we examined conventional toxicological parameters including body weight, clinical chemistry, and histopathology, and also used microarrays to identify gene expression changes in rat liver. High dose nano-copper induced increases in alanine aminotransferase, aspartate aminotransferase, triglyceride, total bilirubin, total bile acid levels, and a decrease in body weight. Histopathological studies of the liver indicated scattered, dotted hepatocytic necrosis in all rats in the high dose nano-copper group. Identified genes from the group receiving the high dose were functionally categorized, and results showed that genes related to oxidoreductase activity, metabolism, and signal transduction were involved in the development of the observed phenotypes. The results also suggest that altered gene expression patterns induced by exposure to a low, subtoxic dose of nano-copper may reveal signs of cell stress or subtle cell injury indicative of overt toxicity at higher doses. Results in this study provide new insights into the toxicology of nano-copper particles and illustrate how toxicogenomic approaches are providing an unprecedented amount of mechanistic information on molecular responses to nano-copper, as well as how they are likely to impact hazard and risk assessment. Gene expression changes are likely to be more sensitive indicators of potential adverse effects than traditional measurements of toxicity.