Increased splicing of CXCR3 isoform B (CXCR3B) by impaired NRF2 signaling leads to melanocyte apoptosis in active vitiligo.

Apoptotic melanocytes (MCs) may release neoantigenic epitopes preceding epidermal infiltration by autoreactive CD8 T cells in early vitiligo. However, the mechanism by which vitiligo MCs are prone to apoptosis under oxidative stress remains elusive. Pro-apoptotic receptor C-X-C motif chemokine receptor 3 isoform B (CXCR3B) is critical for inducing MC apoptosis in the inflammatory microenvironment of lesional vitiligo skin.

Acceleration of melanocyte senescence by the proinflammatory cytokines IFNγ and TNFα impairs the repigmentation response of vitiligo patients to narrowband ultraviolet B (NBUVB) phototherapy.

Vitiligo is a chronic autoimmune disease characterized by the T helper 1 (Th1) cytokine-driven immune destruction of melanocytes (MCs). Although narrowband ultraviolet B (NBUVB) phototherapy has been proven to be an effective therapeutic option, the repigmentation response to that phototherapy varies greatly in different vitiligo patients. Here, we demonstrate that there is an increase of NBUVB-induced cellular senescence in vitiligo MCs exposed to Th1 cytokine interferon γ (IFNγ) and/or tumor necrosis factor α (TNFα) in lesional vitiligo skin from poor responders who had undergone NBUVB phototherapy.

Uncoupling melanogenesis from proliferation in epidermal melanocytes responding to stimulation with psoriasis-related proinflammatory cytokines.

Background: Few studies have addressed the impact of the psoriasis-related proinflammatory cytokines on the proliferation and melanogenesis of melanocytes (MCs) in lesional psoriatic skin.

Objective: We investigated the effects of TNFα, IL17A, and IL8 on the proliferation and melanin synthesis of MCs.

Methods: Skin specimens were biopsied from patients with psoriasis vulgaris at the active stage, or from the tail skin of Dct-LacZ mice with imiquimod (IMQ)-induced psoriasiform dermatitis.

sPmel17 Secreted by Ultraviolet B-Exposed Melanocytes Alters the Intercellular Adhesion of Keratinocytes.

Repigmentation of the skin in patients with vitiligo represents an intricate process in which the depigmented epidermis is replenished by functional melanocytes (MCs) that migrate from undamaged hair follicles and/or surrounding areas. We characterized whether MCs release a secreted form of Pmel17 (sPmel17) protein after exposure to UVB, thereby weakening the cell-cell adhesions of keratinocytes (KCs), which provides MCs the opportunity to migrate to areas devoid of MCs. At first, we examined the interactions of sPmel17 and FHL2 (four-and-a-half LIM domain protein 2) in KCs treated with the conditioned media (CM) from MCs exposed to UVB.

Metformin Promotes the Hair-Inductive Activity of Three-Dimensional Aggregates of Epidermal and Dermal Cells Self-Assembled in vitro.

Introduction: Although it has been reported that the antidiabetic drug metformin has multiple extra-hypoglycemic activities, such as anti-oxidation, antiaging, and even antitumor, topical metformin also can induce hair regeneration, but the precise mechanism involved in that process is still unclear.

Objectives: The aim of this study was to assess the effect of metformin on hair growth in a mouse hair-follicle reconstitution model generated by in vitro self-assembled three-dimensional aggregates of epidermal and dermal cells (DCs) (3D aggregates).

Methods: Epidermal cells and DCs were isolated and cultured from the mouse skin of 50 C57BL/6 mouse pups (1-day-old).

Botulinum toxin A promotes the transdifferentiation of primary keloid myofibroblasts into adipocyte-like cells.

Keloid is a type of unusually raised scar. Botulinum toxin A (BTX-A) has a great application potential in keloids treatment. Here, we investigated the functional role of BTX-A in keloids.

Pro-pigmentary action of 5-fluorouracil through the stimulated secretion of CXCL12 by dermal fibroblasts.

Background: There is growing evidence that 5-fluorouracil (5-FU) combined with therapeutic trauma can effectively induce skin repigmentation in vitiligo patients who are unresponsive to conventional treatments. Previous studies have mainly focused on identifying the antimitotic activity of 5-FU for the treatment of skin cancer, but few studies have investigated its extra-genotoxic actions favoring melanocyte recruitment.

Methods: We utilized the full thickness excisional skin wound model in Dct-LacZ transgenic mice to dynamically assess the migration of melanocytes in the margins of wounds treated with or without 5-FU.

[Updated Molecular Regulation of Hair Growth and Pigmentation by Dermal Papilla Cells].

There is growing evidence that dermal papilla cells(DPCs)act as the organizing center to induce the cyclic hair regeneration.On one hand,DPCs secrete cytokines or growth factors to regulate the differentiation,proliferation,and migration of epithelial stem cells(EpSCs)and melanocyte stem cells(MeSCs)residing in the bulge region.On the other hand,DPCs manipulate the microenvironment(also termed as niche)for both EpSCs and MeSCs,such as the size of dermal papilla,the distance between dermal papilla and the bulge region,and the lymphatic drainage and sympathetic nerve innervation surrounding the bulge region,thereby orchestrating the cycling hair growth.

The regional distribution of melanosomes in the epidermis affords a localized intensive photoprotection for basal keratinocyte stem cells.

Human skin is a highly efficient self-renewing barrier that is critical to withstanding environmental insults. Undifferentiated keratinocyte stem cells reside in the basal layer of the epidermis and in hair follicles that continuously give rise to progenies ensuring epidermal turnover and renewal. Ultraviolet (UV) radiation is a proven cause of skin keratinocyte cancers, which preferentially occur at sun-exposed areas of the skin.

Deciphering skin re-pigmentation patterns in vitiligo: an update on the cellular and molecular events involved.

Current treatment of vitiligo is still a great challenge, since most cases of vitiligo have variable re-pigmentation outcomes due to their unpredictable responses to existing therapeutic regimens. There is an urgent need to identify this re-pigmentation process and to develop novel therapies. This review illustrates the most current research and latest understanding of vitiligo skin re-pigmentation and related regulatory mechanisms.

Role of the p53‑TRPM1/miR‑211‑MMP9 axis in UVB‑induced human melanocyte migration and its potential in repigmentation.

Clinical studies have proven that ultraviolet B (UVB) based phototherapy can induce perifollicular and marginal repigmentation patterns in the skin of vitiligo patients. It is, however, difficult to conceive how melanocytes can easily exit from their tightly interconnected epidermal microenvironment to re‑enter a different location in the skin to establish a new network with neighboring keratinocytes. While it is known that matrix metalloprotease 9 (MMP9) is involved in the degradation of the extracellular matrix in physiological or pathological processes, little is known about whether MMP9 affects melanocyte migration in vitiligo repigmentation.

Intramelanocytic Acidification Plays a Role in the Antimelanogenic and Antioxidative Properties of Vitamin C and Its Derivatives.

Although vitamin C (VC, L-ascorbic acid) has been widely used as a skin lightening agent for a long time, the mechanism by which it inhibits melanogenesis remains poorly understood. It is well-documented that the intramelanocytic pH is an important factor in regulating tyrosinase function and melanosome maturation. The activity of tyrosinase, the rate-limiting enzyme required for melanin synthesis, is generally minimal in an acidic environment.

Abnormalities in endothelial form of nitric oxide synthase is pathogenic in limited cutaneous systemic sclerosis.

Background: Limited cutaneous systemic sclerosis is one subtype of systemic sclerosis which is characterized by a prototypic multisystem fibrotic disorder.

Objective: This study aimed to further investigate the pathological mechanism of limited cutaneous systemic sclerosis (lcSSc).

Methods: The dataset GSE76807 generated from 10 lcSSc patients and five healthy controls was used.

Inhibitory effect of timolol on topical glucocorticoid‑induced skin telangiectasia.

The aim of the present study wasto investigate the potential inhibitory effect of timolol on topical glucocorticoid‑induced skin telangiectasia. In rabbits, flumethasone ointment was used to induce skin telangiectasia in the inner ear. Subsequently, timolol maleate (0.

Degraded melanocores are incompetent to protect epidermal keratinocytes against UV damage.

Melanosomes are membrane-bound intracellular organelles that are uniquely generated by melanocytes (MCs) in the basal layer of human epidermis. Highly pigmented mature melanosomes are transferred from MCs to keratinocytes (KCs), and then positioned in the supra-nuclear region to ensure protection against ultraviolet radiation (UVR). However, the molecular mechanism underlying melanosome (or melanin pigment) transfer remains enigmatic.

Baicalin increases hair follicle development by increasing canonical Wnt/β‑catenin signaling and activating dermal papillar cells in mice.

Baicalin is a traditional Chinese herbal medicine commonly used for hair loss, the precise molecular mechanism of which is unknown. In the present study, the mechanism of baicalin was investigated via the topical application of baicalin to reconstituted hair follicles on mice dorsa and evaluating the effect on canonical Wnt/β‑catenin signaling in the hair follicles and the activity of dermal papillar cells. The results indicate that baicalin stimulates the expression of Wnt3a, Wnt5a, frizzled 7 and disheveled 2 whilst inhibiting the Axin/casein kinase 1α/adenomatous polyposis coli/glycogen synthase kinase 3β degradation complex, leading to accumulation of β‑catenin and activation of Wnt/β‑catenin signaling.

Induction of retinal-dependent calcium influx in human melanocytes by UVA or UVB radiation contributes to the stimulation of melanosome transfer.

Objectives: The transfer of melanosomes from melanocytes to neighbouring keratinocytes is critical to protect the skin from the deleterious effects of ultraviolet A (UVA) and ultraviolet B (UVB) irradiation; however, the initial factor(s) that stimulates melanosome transfer remains unclear. In this study, we investigated the induction of retinal-dependent calcium (Ca ) influx in melanocytes (MCs) by UVA or UVB irradiation and the effect of transient receptor potential cation channel subfamily M member 1 (TRPM1) (melastatin1)-related Ca influx on melanosome transfer.

Materials And Methods: Primary human epidermal MCs were exposed to physiological doses of UVB or UVA light and loaded with a calcium indicator Fluo-4 dye.

Deoxyarbutin Possesses a Potent Skin-Lightening Capacity with No Discernible Cytotoxicity against Melanosomes.

Safe and effective ingredients capable of removing undesired hyperpigmentation from facial skin are urgently needed for both pharmaceutical and cosmetic purposes. Deoxyarbutin (4-[(tetrahydro-2H-pyran-2-yl) oxy] phenol, D-Arb) is a glucoside derivative of hydroquinone. Here, we investigated the toxicity and efficacy of D-Arb at the sub-cellular level (directly on melanosomes) and skin pigmentation using in vivo and in vitro models to compare with its parent compound hydroquinone (1,4-benzenediol, HQ).

Efficacy of Ganglioside GM1 in the Treatment of Postherpetic Neuralgia.

Postherpetic neuralgia (PHN) is a commonest and difficult-to-manage complication of Herpes zoster. This comparative study included 140 cases of PHN admitted in the department of dermatology in Renmin Hospital of Wuhan University, Wuhan, China, from March 2014 to February 2015, divided into a control and a study group. In addition to the combination of antiviral, analgesic, and neurotrophic agents given to the control group, additional ganglioside GM1 was given to patients in the study group.

Adipose‑derived mesenchymal stem cell‑facilitated TRAIL expression in melanoma treatment in vitro.

Adipose-derived stem cells (ADSCs) may be useful as an efficient vehicle in cell-based gene therapy of human diseases due to their ability to migrate to disease lesions. This study investigated the ability of ADSC‑harbored human tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) cDNA to facilitate TRAIL expression and induce A375 melanoma cell apoptosis as observed using a Transwell co‑culture system. A cell migration assay was used to observe ADSC migration ability.

Asymmetric stem-cell division ensures sustained keratinocyte hyperproliferation in psoriatic skin lesions.

Excessive expansion of the transit-amplifying (TA) cell compartment is a distinct morphological characteristic of psoriatic epidermal hyperplasia. In order to examine the activation of basal stem cells and how they replenish such an enlarged compartment of TA cells in psoriatic epidermis, we utilized a BrdU labeling method to monitor mitotic stem cells in a mouse model of psoriasiform dermatitis, which was induced by imiquimod. Our results showed that perpendicular and parallel cell division characteristics of dividing stem cells existed in the inflamed epidermis.

The multi-lineage differentiation and angiogenesis ability of adipose-derived adult mesenchymal stem cells.

Background: To investigate the in vitro multi-lineage differentiation of adipose-derived adult stem cells and their ability to differentiate into endothelial cells.

Methods: Adipose-derived adult stem cells were isolated for detection of the immune phenotype, cell doubling time, cycle, and induction of endothelial cell differentiation in vitro. The expression of endothelial cell-specific surface markers was measured immunocytochemically.

Primary cutaneous nocardiosis.

Nocardiosis is a rare human infection due to ubiquitous soil born gram-positive, filametous aerobic bacteria. First signs are frequently cutaneous either as part of systemic infection disseminated to the skin, or as primary cutaneous inoculation. An 88 years old man presented with a 3-day history of red papules and pustules with pain on his forehead.