Corrigendum: The Effect of Micro-Spicule Containing Epidermal Growth Factor on Periocular Wrinkles.

[This corrects the article on p. 187 in vol. 29, PMID: 28392646.].

The Effect of Micro-Spicule Containing Epidermal Growth Factor on Periocular Wrinkles.

BACKGROUND: Micro-needle patches have been recently used to increase skin permeability, which improves drug delivery, and for cosmetic purposes. However, these patches may often have limited efficacy due to insufficient skin penetration and reduced compliance caused by discomfort. OBJECTIVE: We evaluated the efficacy and the safety of soluble micro-spicule containing epidermal growth factor (MS-EGF) for the treatment of periocular wrinkles. METHODS: Twenty healthy volunteers aged 33 to 54 years were enrolled in a randomized, controlled, split-face study. For 4 weeks, a periocular wrinkle was treated daily with either a soluble MS-EGF cream or a cream containing EGF alone. All subjects underwent 8 weeks of follow-up. Efficacy was assessed using an ultrasonic measurement of dermal depth and density, digital skin image analysis, 5-point photonumeric scale for periocular wrinkles and subjective satisfaction. RESULTS: MS-EGF group showed statistically significant increase of dermal depth and density compared to EGF alone group after 4 and 8 weeks. In addition, there was a marked improvement shown in clinical and 3-dimensional skin image in MS-EGF group. The treatments were well-tolerated; no significant side-effect was noted. CONCLUSION: The MS-EGF formulation may represent an effective and biocompatible advance in the treatment of periocular wrinkles.

Congenital lipedematous alopecia: adding to the differential diagnosis of congenital alopecia.

Lipedematous alopecia is a rare condition of unknown etiology characterized by a thick boggy scalp with varying degrees of hair loss. It is usually seen in adult African-American females, and a case in a 9-year-old was the youngest patient reported thus far. We report on the appearance of this condition in two children, a 6-year-old child and a 10-year-old child. Each presented with congenital patchy hair loss on the occipital area and the left temple. A boggy hairless scalp with soft swelling was detected in both patients. Histological examination showed increased thickness of the subcutaneous fat tissue with a decrease in hair follicles. These features were consistent with a diagnosis of lipedematous alopecia. We report two cases of congenital lipedematous alopecia, which has not been reported previously. Although congenital, these distinct clinical features should be kept in mind in the diagnosis of alopecic hair loss.

Effect of adenosine on melanogenesis in b16 cells and zebrafish.

BACKGROUND: Adenosine is a nucleoside, in which an adenine molecule is attached to a ribofuranose sugar moiety. It can be released into the microenvironment by metabolically active cells, and then fulfills a multitude of functions in regulation of cell proliferation, by activating four subtypes of G protein-coupled adenosine receptors. OBJECTIVE: In this study, we investigated the effect of adenosine on melanogenesis, using B16 melanoma cells. METHODS: The toxic effects of adenosine on B16 melanoma cells were assessed. To understand the mechanism of the effect of adenosine on melanogenesis in B16 cells, melanin content and tyrosinase activity were measured. Tyrosinase, tyrosinase-related protein-1, and dopachrome tautomerase were monitored by Western blotting. Finally, adenosine was applied to zebrafish embryos, and its in vivo effect on pigmentation investigated. RESULTS: At a low concentration, adenosine increased melanin content and tyrosinase activity, while a high dose of adenosine resulted in inhibition of tyrosinase activity. Western blotting showed that adenosine increased tyrosinase protein levels slightly, while high-dose adenosine decreased the expression of tyrosinase. In zebrafish tests, adenosine slightly inhibited body pigmentation. CONCLUSION: In this study, we investigated the effect of adenosine on melanogenesis, using the well-established B16 melanoma cell and zebrafish models. The results suggest that adenosine may inhibit pigmentation, through negative regulation of tyrosinase.

Propionibacterium acnes activates the NLRP3 inflammasome in human sebocytes.

Propionibacterium acne and sebaceous glands are considered to have an important role in the development of acne. Although information regarding the activation of innate immunity by P. acnes in the sebaceous gland is limited, different P. acnes phylotypes and a higher prevalence of follicular P. acnes macrocolonies/biofilms in sebaceous follicles of skin biopsies from acne compared with control skin and occasionally single P. acnes clusters in single sebaceous glands have been detected. In this study, we investigated whether P. acnes activates the inflammasome in human sebaceous glands in vivo and in vitro. We found that IL-1ß expression was upregulated in sebaceous glands of acne lesions. After stimulation of human sebocytes with P. acnes, the activation of caspase-1 and secretion of IL-1ß were enhanced significantly. Moreover, knocking down the expression of NLRP3 abolished P. acnes-induced IL-1ß production in sebocytes. The activation of the NLRP3 inflammasome by P. acnes was dependent on protease activity and reactive oxygen species generation. Finally, we found that NALP3-deficient mice display an impaired inflammatory response to P. acnes. These results suggest that human sebocytes are important immunocompetent cells that induce the NLRP3 inflammasome, and that P. acnes-induced IL-1ß activation in sebaceous glands may have a role in combating skin infections and in acne pathogenesis.

Nrf2 negatively regulates melanogenesis by modulating PI3K/Akt signaling.

Nrf2 plays a role in protection of cells against oxidative stress and xenobiotic damage by regulating cytoprotective genes. In this study, we investigated the effect of Nrf2 on melanogenesis in normal human melanocytes (NHMCs). When NHMCs were transduced with a recombinant adenovirus expressing Nrf2, melanin synthesis was significantly decreased. Consistent with this result, overexpression of Nrf2 decreased the expression of tyrosinase and tyrosinase-related protein 1. The inhibitory effect of Nrf2 was reversed by overexpression of Keap1, an intracellular regulator of Nrf2. Interestingly, Nrf2 overexpression resulted in marked activation of PI3K/Akt signaling. Conversely, inhibition of PI3K activity by treatment with wortmannin reversed the depigmentary effects of Nrf2. Taken together, these results strongly suggest that Nrf2 negatively regulates melanogenesis by modulating the PI3K/Akt signaling pathway.

Clinical significance of serum high-mobility group box 1 level in alopecia areata.

BACKGROUND: Alopecia areata (AA), a chronic, relapsing hair-loss disorder, is considered to be a T-cell-mediated autoimmune disease. High-mobility group box 1 (HMGB1), released by necrotic cells and in response to various inflammatory stimuli, is currently considered to be a significant target antigen in diverse autoimmune diseases. OBJECTIVE: We sought to investigate the clinical significance of serum HMGB1 levels in AA. METHODS: We compared levels of HMGB1 in scalp specimens from 7 patients with AA and 8 healthy control subjects and in blood samples from 45 patients with AA and 10 healthy control subjects. Moreover, we evaluated the correlation between HMGB1 level and clinical severity. RESULTS: Immunohistochemical staining of scalp tissues from patients with AA revealed higher HMGB1 levels than in healthy control subjects. In addition, serum HMGB1 levels in the AA group were generally higher, and showed concordance with the patients' clinical characteristics, including onset, hair-pull test results, and treatment response. LIMITATIONS: The number of patients and healthy control subjects evaluated was small. CONCLUSION: These results suggest that HMGB1 plays a significant role in the pathogenesis of AA, and that it is a promising predictor of prognosis and treatment response. Moreover, this study identifies a new potential therapeutic target for the treatment of AA.

S100A8 and S100A9 are messengers in the crosstalk between epidermis and dermis modulating a psoriatic milieu in human skin.

S100A8 and S100A9 are members of the S100A8 protein family that exist as homodimers and heterodimers in neutrophils, monocytes, and macrophages. Recent studies have shown the pivotal roles of S100A8 and S100A9 in the propagation of inflammation and keratinocyte proliferation in psoriasis. We found significant up-regulation of S100A8 and S100A9 secretion from keratinocytes in psoriatic lesions. To mimic the in vivo secretory conditions of S100A8 and S100A9 from psoriatic epidermal keratinocytes, we used the culture medium (CM) of S100A8 and S100A8/A9 adenovirus-transduced keratinocytes to investigate the functions of S100A8 and S100A9. We detected increased levels of various pro-inflammatory cytokines in the CM, including IL-8 and TNF-α, which are involved in aggravating psoriatic skin lesions, and IL-6 and members of the CXCL family of pro-angiogenic cytokines. The CM increased immune cell migration and increased angiogenesis in human umbilical vein endothelial cells. In conclusion, we found that the upregulated production of S100A8 and S100A9 by psoriatic epidermal keratinocytes activated adjacent keratinocytes to produce several cytokines. Moreover, S100A8 and S100A9 themselves function as pro-angiogenic and chemotactic factors, generating a psoriatic milieu in skin.