Retinyl retinoate applied twice daily was significantly more effective than a placebo or retinol in treating periorbital wrinkles. Importantly, no severe side-effects were observed.
Leptin is a protein hormone produced by adipocytes. It is secreted into the blood stream and plays a key role in regulating body energy homeostasis by inhibiting feeding behavior followed by decreased body weight. Because protein aggregation is a major problem in therapeutic proteins, we previously demonstrated that a stabilizing peptide (SP) fusion protein of leptin (SP-leptin) appeared to resist aggregation induced by agitation, freezing/thawing, or heat stress. In this study, we fused mouse leptin with the stabilizing peptide and compared the biological activities of leptin and SP-leptin in vivo using a male C57Bl mouse model and ex vivo using MCF7 breast cancer cell lines. Each group of mice was treated with saline, leptin, and SP-leptin for 20 days and the differences in body weight, food intake, abdominal fat contents, and TG concentration were measured. The SP-leptin appeared to decrease the body weight and food intake in male C57Bl mice more significantly than wild type leptin, and the SP-leptin treated MCF7 cells displayed better cell proliferation than leptin. As a consequence of decreased body weight, the SP-leptin treated mouse group showed decreased abdominal fat contents and low triglyceride (TG) concentration. Moreover, the SP-leptin treated mouse group had fewer lipid droplets in liver and reduced lipid droplet size when analyzed by Oil red O and H & E staining. These results demonstrated that SP-leptin is more effective than wild type leptin in normal mice in lowering their body weight and fat contents in the abdominal region, the serum, and the liver.
Treatment with ruxolitinib cream (Janus kinase [JAK] 1/JAK2 inhibitor) in adult patients with vitiligo resulted in substantial repigmentation over 52 weeks in a phase 2 dose-ranging study (NCT03099304). We assessed maintenance of repigmentation among responders from the phase 2 study following ruxolitinib discontinuation after 104 weeks of treatment. Patients initially randomized to ruxolitinib cream (1.5% twice daily [BID], 1.5% once daily [QD], 0.5% QD, or 0.15% QD) with evidence of facial repigmentation at Week 24 who completed 1 follow-up visit 1, 3, or 6 months after an additional 52 weeks of 1.5% ruxolitinib cream BID (Weeks 52e104) were analyzed. Loss of repigmentation was defined as an increase in Vitiligo Area Severity Index score during the last follow-up visit vs Week 104 on ruxolitinib cream. The analysis included 16 patients (1.5% BID, n¼3; 1.5% QD, n¼5; 0.5% QD, n¼3; 0.15% QD, n¼5 [including 2 patients rerandomized to 1.5% BID/0.5% QD after Week 24]). Twelve patients (75.0%) maintained total body repigmentation and 13 (81.3%) maintained facial repigmentation during follow-up of 1e6 months; no patients from the 1.5% ruxolitinib BID treatment group (with 2 years' exposure) experienced repigmentation loss. There were no significant differences in baseline serum levels of chemokine (C-X-C motif) ligand (CXCL) 9, CXCL10, or interleukin-15 in patients who experienced loss vs maintenance of repigmentation after ruxolitinib cream discontinuation. This exploratory analysis suggests that some repigmentation with ruxolitinib cream may be maintained post-discontinuation; larger follow-up studies are required to confirm these findings.
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