Pigment Cell & Melanoma Research最新文献

Childhood vitiligo, distinct from its adult counterpart, presents unique treatment challenges. Glycyrrhizin inhibits the release of high-mobility group box 1 (HMGB1) protein from keratinocytes, preventing melanocyte apoptosis and autophagy. Furthermore, the orally administered compound glycyrrhizin (OCG) effectively treats various autoimmune disorders, demonstrating long-term efficacy, safety, and tolerability. This study compared the efficacy of OCG and oral prednisone (OP), followed by phototherapy, in patients with progressive childhood vitiligo at 52 weeks' follow-up. Fifty children with vitiligo were randomized into two groups according to treatment: OCG (50–150 mg/day) followed by phototherapy (n = 25) and OP (5–10 mg/day) followed by phototherapy (n = 25). At Week 24, a halt in disease progression (HDP) was observed in 20 (80%) patients in the OCG group and 21 (84%) in the OP group, with no significant difference (p > 0.99). However, the mean time to achieve HDP was significantly shorter in the OP group than in the OCG group (14.73 ± 4.84 vs. 19.13 ± 4.82 weeks; p < 0.01). In addition, serum HMGB1 concentrations were significantly reduced after treatment with OCG at Week 24 (3.02 ± 0.83 vs. 0.95 ± 0.36 ng/mL [p < 0.01]; OP, 2.79 ± 0.16 vs. 1.03 ± 0.34 ng/mL [p < 0.01]). The decline in Vitiligo Area Scoring Index (VASI) score at the end of follow-up (i.e., Week 52) did not show a statistically significant difference between the OCG and OP groups (52.31% ± 14.86% vs. 55.71% ± 21.23%; p = 0.55). The therapeutic response of the clinical markers of progression was good and comparable between the OCG and OP groups. OCG demonstrated similar efficacy to OP followed by phototherapy in controlling disease activity and promoting repigmentation in children with vitiligo at 52 weeks of follow-up.

Trial Registration: ChiCTR2400086844

Vitiligo pathogenesis is complex. There is some evidence in support of the neurohormonal pathways involved. Although considered a nonpruritic condition, some patients may experience itching, which can occur ahead of the appearance of the patches. We aimed to assess sensory symptoms in active and stable vitiligo patients and to measure 3 neuropeptide expressions in their lesional skin (neuropeptide Y [NPY], calcitonin gene–related peptide [CGRP], and nerve growth factors [NGF]) to correlate neuropeptide levels and sensory symptoms, with vitiligo activity. This case–control study included 85 patients, aged 18 years and older, analyzed into active or stable vitiligo groups. Patients were screened for itching or other abnormal neurological sensations such as paresthesia and numbness. The Vitiligo Disease Activity Score, Vitiligo Signs of Activity Score, and dermoscopic score were performed to assess disease activity. Three neuropeptides were quantified by enzyme-linked immunosorbent assay in skin biopsies from the edge of vitiligo lesions. A normal control group was also included. Results showed that 24.7% of patients had sensory symptoms: itching (18.8%), paresthesia (2.4%), and numbness (3.5%). The NGF, CGRP, and NPY levels were significantly higher in skin of normal controls compared to stable and active vitiligo patients. They were lowest in active vitiligo skin (p = 0.001, 0.016, and 0.01, respectively). NGF was the most relevant neuropeptide to vitiligo activity and sensory manifestations. In conclusion, almost one-third of the patients with active vitiligo reported sensory symptoms, predominantly itching, thus sensory manifestations may suggest a prodroma of activity and could be included in the screening tools for vitiligo activity.

Trial Registration: www.clinicaltrials.gov (NCT05390164).

Epidermal melanocytes form synaptic-like contacts with cutaneous nerve fibers, but the functional outcome of these connections remains elusive. In this pilot study we used our fully humanized re-innervated skin organ culture model to investigate melanocyte-nerve fiber interactions in UV-B-induced melanogenesis. UV-B-irradiation significantly enhanced melanin content and tyrosinase activity in re-innervated skin compared to non-innervated controls, indicating that neuronal presence is essential for exacerbating pigmentation upon UV-B irradiation in long-term culture. Comparative transcriptomic analysis between laser-capture-microdissected melanocytes from freshly embedded human skin and published microarray data on in vitro primary melanocytes identified Semaphorin-4A (SEMA4A) as possible mediator of melanocyte-nerve fibers interactions. SEMA4A protein levels in Gp100⁺-epidermal melanocytes were significantly higher in re-innervated skin, and reduced by UV-B treatment. Analysis of melanocytes in vitro showed reduced SEMA4A protein expression 24 h after UV-B-irradiation while SEMA4A secretion into the medium was increased. Beta-tubulin expression and axon growth in sensory neurons were stimulated by conditioned media (CM) from UV-B irradiated melanocytes. When this neuronal-conditioned medium was transferred to fresh melanocytes, melanin content increased, but only if neurons had been treated with CM from UV-B irradiated melanocytes. These findings highlight the importance of melanocyte-neuron interactions for UV-B-induced melanogenesis and suggest that secreted proteins (e.g., SEMA4A) can function as a novel target to treat hypo- and hyperpigmentation disorders.

Beta-blockers have generated an exciting discourse for their potential as a cheap, safe, and effective adjunctive therapy for cutaneous melanoma patients, but the field remains murky. This systematic review investigates the association between beta-blocker use and survival outcomes in cutaneous melanoma patients. We reviewed 12 studies with 21,582 patients in a network meta-analysis and found a benefit between beta-blocker use and disease-free survival but no other significant association for melanoma-specific or overall survival. However, some evidence suggests that pan-selective beta-blockers, rather than cardio-selective ones, may have a protective effect. We conclude that the current evidence is insufficient to recommend beta-blockers for melanoma treatment but suggest further research focusing on pan-selective beta-blockers to clarify their potential benefits.