The diagnostic value of in vivo reflectance confocal microscopy in actinic keratosis.

BACKGROUND: Actinic keratosis (AK) is a pre-neoplastic skin damage caused by sun exposure with a risk of transforming squamous cell carcinoma (SCC) ranging from 0.1%-20%, while it should be differentiated with many diseases such as seborrheic keratosis (SK), discoid lupus erythematosus (DLE), Bowen's disease, and basal cell carcinoma(BCC) et al. Reflectance confocal microscopy (RCM) as a non-invasive method is showing an increasing diagnostic accuracy. Currently, there are a few studies that summarized the characteristics of AK with RCM. AIM: The study aimed to find the diagnostic value of diagnosing actinic keratosis by reflectance confocal microscopy. METHODS: A total of 92 patients with clinical suspicious diagnosis of actinic keratosis were enrolled in this study, and RCM device imaged their lesions. Fifty-three of these patients underwent skin biopsies to confirm the diagnosis. We retrospectively analyzed the results of RCM and histological diagnosis and then summarized the RCM characteristics of biopsy-confirmed lesions. RESULTS: Based on RCM images, 76 of 92 (82.6%) patients were diagnosed with AK, 9 of 92 (9.8%) patients could not be diagnosed by the dermatologist according to RCM. Of all 53 biopsied lesions, 42 (79.2%) were AK, 1 was seborrheic keratosis, 3 were basal cell carcinoma, three were discoid lupus erythematosus, 1 was Bowen's disease, and three were squamous cell carcinoma. CONCLUSION: The value of RCM in the diagnosis and differential diagnosis of AK is good and worthy of clinical application.

Successful and quick treatment of nevus of Ota with 755nm picosecond laser in Chinese.

Nevus of Ota, also known as nevus fusco-caeruleus ophthalmo-maxillaris, is a benign dermal melanocytosis. In the past, this disease was usually treated by Q-switched laser therapy, but the course of treatment was relatively long. In recent years, it has been reported that 755nm picosecond laser, which was firstly reported to treat tattoos, is also effective in the treatment of nevus of Ota. Here, we report six cases of nevus of Ota which were treated with 755nm picosecond laser in Chinese people. We find amazingly that these lesions almost disappeared after only one or two sessions of treatment.

Roles of inflammation factors in melanogenesis (Review).

The occurrence of hyperpigmentation or hypopigmentation after inflammation is a common condition in dermatology and cosmetology. Since the exact mechanism of its occurrence is not yet known, prevention and treatment are troublesome. Previous studies have confirmed that α­melanocyte­stimulating hormone, stem cell factor and other factors can promote melanogenesis­related gene expression through the activation of signaling pathways. Recent studies have revealed that a variety of inflammatory mediators can also participate in the regulation of melanogenesis in melanocytes. In this review, we summarized that interleukin­18, interleukin­33, granulocyte­macrophage colony stimulating factor, interferon­Î³, prostaglandin E2 have the effect of promoting melanogenesis, while interleukin­1, interleukin­4, interleukin­6, interleukin­17 and tumor necrosis factor can inhibit melanogenesis. Further studies have found that these inflammatory factors may activate or inhibit melanogenesis­related signaling pathways (such as protein kinase A and mitogen activated protein kinase) by binding to corresponding receptors, thereby promoting or inhibiting the expression of melanogenesis­related genes and regulating skin pigmentation processes. This suggests that the development of drugs or treatment methods from the perspective of regulating inflammation can provide new ideas and new targets for the treatment of pigmented dermatosis. This review outlines the current understanding of the inflammation factors' roles in melanogenesis.

The Long Noncoding RNA UCA1 Negatively Regulates Melanogenesis in Melanocytes.

The long noncoding RNA UCA1 was first discovered in bladder cancer and is known to regulate the proliferation and migration of melanoma. However, its role in melanogenesis is unclear. In this study, we aimed to explore the role and mechanism of UCA1 in melanogenesis. Our findings showed that the expression of UCA1 was negatively correlated with melanin content in melanocytes and pigmented nevus. Overexpression of UCA1 in melanocytes decreased melanin content and the expression of melanogenesis-related genes, whereas knockdown of UCA1 in melanocytes had the opposite effect. High-throughput sequencing revealed that microphthalmia-associated transcription factor (MITF), an important transcription factor affecting melanogenesis, was also negatively correlated with the expression of UCA1. Furthermore, the transcription factor CRE-binding protein (CREB), which promotes MITF expression, was negatively regulated by UCA1. The cAMP/protein kinase A (PKA), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) signaling pathways, which are upstream of the CREB/MITF/melanogenesis axis, were activated or inhibited in response to silencing or enhancing UCA1 expression, respectively. In addition, enhanced UCA1 expression downregulates the expression of melanogenesis-related genes induced by UVB in melanocytes. In conclusion, UCA1 may negatively regulate the CREB/MITF/melanogenesis axis through inhibiting the cAMP/PKA, ERK, and JNK signaling pathways in melanocytes. UCA1 may be a potential therapeutic target for the treatment of pigmented skin diseases.

Ganoderma lucidum polysaccharide reduces melanogenesis by inhibiting the paracrine effects of keratinocytes and fibroblasts via IL-6/STAT3/FGF2 pathway.

Our previous study found that Ganoderma lucidum polysaccharide (GLP), bioactive ingredients from Ganoderma lucidum, protected fibroblasts from photoaging. However, whether GLP can affect melanogenesis in melanocytes through regulating paracrine mediators that secreted by keratinocytes and fibroblasts is unclear. We aimed to investigate the efficacy and mechanisms of action of GLP in melanogenesis by regulating paracrine effects of keratinocytes and fibroblasts. The effect of GLP on cell viability affected by GLP was measured by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. After an immortal keratinocyte line (HaCaT) and primary fibroblasts (FB) were treated with GLP, the supernatants of HaCaT and FB cells were collected and cocultured with an immortalized melanocyte line (PIG1). The expression levels of melanogenesis-associated genes in PIG1 cells were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis. Furthermore, FRS-2, ERK, JNK, and p38 phosphorylation levels were measured. Then, major melanogenic paracrine mediators in HaCaT and FB cells treated with GLP were evaluated by qRT-PCR and enzyme-linked immunosorbent assay (ELISA). In addition, the expression of IL-6 and STAT3 was examined in HaCaT and FB cells. GLP was not cytotoxic to HaCaT and FB cells. The supernatants of GLP-treated HaCaT and FB cells downregulated the expression levels of MITF, TYR, TYRP1, TYRP2, RAB27A, and FSCN1 genes and inhibited the phosphorylation of FRS-2, ERK, JNK, and p38 in PIG1 cells. GLP also decreased FGF2 secretion in HaCaT and FB cells. Moreover, GLP reduced IL-6 expression and STAT3 phosphorylation in HaCaT and FB cells. GLP reduced melanogenesis in melanocytes by inhibiting the paracrine effects of keratinocytes and fibroblasts via IL-6/STAT3/FGF2 pathway.

Ganoderma lucidum polysaccharide inhibits UVB-induced melanogenesis by antagonizing cAMP/PKA and ROS/MAPK signaling pathways.

Ultraviolet (UV)-induced pigmentation is very common in clinical practice, but the current treatments are rarely effective, accompanied by some side effects. Ganoderma lucidum polysaccharide (GLP) is a natural antioxidant with no toxic side effects, which can antagonize UVB-induced fibroblast photo aging. The study aims to explore the role of GLP in inhibiting UVB-induced melanogenesis and its possible mechanism. The expression of melanogenesis genes such as microphthalmia-associated transcription factor (MITF), tyrosine (TYR), tyrosinase related protein 1 (TYRP1), tyrosinase related protein 2 (TYRP2), ras-related protein Rab-27A (Rab27A), and Myosin shows an upward trend after exposure of B16F10 and PIG1 cells to UVB irradiation, but GLP can downregulate the expression of genes related to UVB-induced melanogenesis. GLP can inhibit UVB-activated protein kinase A (PKA) and mitogen-activated protein kinase (MAPK) signaling pathways. Besides, GLP protects mitochondria from UVB damage and inhibits reactive oxygen species (ROS) production. Also, UVB-induced cyclic adenosine monophosphate (cAMP) can be inhibited. It has been found in the experiments of UVB-induced skin pigmentation in zebrafish that GLP is capable of inhibiting UVB-induced skin pigmentation. Meanwhile, it can greatly relieve erythema reaction in guinea pig skin caused by high-dosage UVB irradiation. In conclusion, this study shows that GLP can inhibit UVB-induced melanogenesis by antagonizing cAMP/PKA and ROS/MAPK signaling pathways and is a potential natural safe whitening sunscreen additive.

Functions and regulatory mechanisms of metastasis-associated lung adenocarcinoma transcript 1.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long noncoding RNA whose transcript is around 8 kb in length. As an important stress response molecule, MALAT1 can be expressed differently under stress conditions, such as hypoxia, high glucose, hydrogen peroxide, ultraviolet irradiation, infection, and chemical stimulation. MALAT1 is involved in regulating multiple cell behaviors, such as proliferation, apoptosis, differentiation, migration, epithelial-mesenchymal transition, autophagy, and morphological maintenance. Extensive evidence show that MALAT1 plays critical roles in the physiopathological process of embryo implantation, angiogenesis, tissue inflammation, tumor progression, liver fibrosis, cardiovascular remodeling, and diabetes progression by regulating gene transcription, forming RNA-protein complexes with proteins as a structural component, regulating protein activity, assisting protein localization, mediating epigenetic changes, or by acting as a competing endogenous RNA. Furthermore, MALAT1 can affect the sensitivity of chemotherapy and radiotherapy; therefore, it could be used as a potential drug target for chemotherapy and radiotherapy sensitization. The levels of MALAT1 are reported to be overexpressed in most tumor tissues or sera, and the expression levels of MALAT1 often affect the tumor size, stage, lymph node metastasis, and distant invasion. Therefore, MALAT1 can be used as a biomarker for early diagnosis, severity assessment, or prognostic assessment. This review outlines the current understanding of the biological role and function of MALAT1. In the meantime, we have summarized the mechanisms involved in the reulation of MALAT1 expression and the mechanisms by which MALAT1 regulates the physiological and pathological processes.

MALAT1 participates in ultraviolet B-induced photo-aging via regulation of the ERK/MAPK signaling pathway.

Long non-coding RNA (lncRNA), transcripts of >200 bp in length that do not appear to exhibit any coding capacity, are important in the occurrence and development of cancer, cardiovascular and neurological diseases. However, effects of lncRNAs on photo­aging remain to be elucidated. To explore the potential effects of the lncRNA metastasis­associated lung adenocarcinoma transcript 1 (MALAT1) on photo­aging in fibroblasts, MALAT1 expression was silenced in fibroblasts using small interference RNA. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was used to examine MALAT1 expression in normal and silenced fibroblasts following irradiation with 60 mJ/cm2 ultraviolet B (UVB) and an ELISA assay was used to identify matrix metalloproteinase­1 (MMP­1) content in the cellular supernatant. A ß-galactosidase kit was applied to measure the number of senescent cells and a western blot assay was used to detect extracellular signal­regulated kinase (ERK), c­Jun N­terminal kinase (JNK) and p38 phosphorylation levels. RT­qPCR was additionally used to detect changes in MALAT1 expression following suppression of UVB­induced reactive oxygen species (ROS) generation with N­acetyl­L­cysteine (NAC). Fibroblasts irradiated with 60 mJ/cm2 UVB demonstrated increased MALAT1 expression, MMP­1 secretory volume and number of senescent cells, and greater levels of ERK, p38 and JNK phosphorylation. Following silencing of MALAT1 expression in photo­aged fibroblasts, decreases were observed in MMP­1 secretory volume, number of senescent cells and phosphorylation levels of ERK. NAC reduced ROS content, however, it did not affect MALAT1 expression. Therefore, it was concluded that MALAT1 may participate in UVB­induced photo­aging via regulation of the ERK/mitogen­activated protein kinase signaling pathway and UVB­induced MALAT1 expression is independent of ROS generation.

Effect of borneol on the transdermal permeation of drugs with differing lipophilicity and molecular organization of stratum corneum lipids.

The aim of the present paper was to investigate the promoting activity of borneol on the transdermal permeation of drugs with differing lipophilicity, and probe its alterations in molecular organization of stratum corneum (SC) lipids. The toxicity of borneol was evaluated in epidermal keratinocyte HaCaT and dermal fibroblast CCC-HSF-1 cell cultures and compared to known enhancers, and its irritant profile was also assessed by transepidermal water loss (TEWL) evaluation. The promoting effect of borneol on the transdermal permeation of five model drugs, namely 5-fluorouracil, antipyrine, aspirin, salicylic acid and ibuprofen, which were selected based on their lipophilicity denoted by logp value, were performed using in vitro skin permeation studies. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) was employed to monitor the borneol-induced alteration in molecular organization of SC lipids. The enhancer borneol displayed lower cytotoxicity or irritation in comparison to the well-established and standard enhancer Azone. Borneol could effectively promote the transdermal permeation of five model drugs, and its enhancement ratios were found to be parabolic curve with the logp values of drugs, which exhibited the optimum permeation activity for relatively hydrophilic drugs (an estimated logp value of -0.5 ∼0.5). The molecular mechanism studies suggested that borneol could perturb the structure of SC lipid alkyl chains, and extract part of SC lipids, resulting in the alteration in the skin permeability barrier.

[Depression in patients with facial acne vulgaris and the influential factors].

OBJECTIVE: To understand the influential factors for depression in patients with facial acne vulgaris and to provide scientific evidence for a comprehensive and systematic treatment for acne vulgaris.
 METHODS: A total of 287 outpatients with facial acne vulgaris, who visited the dermatology of the Third Xiangya Hospital, were surveyed by Beck Depression Inventory (BDI). The data was collected by Epidata software (version 3.1) and processed by SPSS software package (version 18.0). The influential factors for the depression of outpatients with facial acne vulgaris were analyzed by multinomial logistic regression.
 RESULTS: A total of 181 patients with facial acne vulgaris showed various degrees of depression (BDI score≥5) and the rate was 63.1%. The symptoms for depression included sad and pessimistic attitude as well as the decreased attention to others (social withdrawal). The influential factors for mild, moderate or severe depression were gender, the degree and the course of acne. Female patients were more likely to suffer mild, moderate or severe depression (OR=3.62, 2.63, respectively); the risk of depression in acne patients was increased with the increase in degree of the severity (OR=2.31, 4.51, respectively); the patients with the acne course more than a year were more likely to show mild depression than those with a course less than a year (OR=4.30, 7.44, respectively). The patients with acne course more than 3 years were more likely to show moderate or severe depression compared to those with a course less than a year (OR=3.60).
 CONCLUSION: Most of facial acne patients show a different degree of depression. The acne course is longer in female patients. The more severe the acne vulgaris is, the more suffering of the depression is. Psychological care should be considered to improve the treatment and quality of life.

The combination of CO2 laser vaporation and photodynamic therapy in treatment of condylomata acuminata.

The aim of this study was to investigate the effectiveness of CO2 laser vaporation and topical PDT combination on condylomata acuminate (CA) located in the perianal and external genital area. A total of 119 patients (perianal CA=52 cases and external genital CA=67 cases) with at least one CA lesion >2mm were treated with monopulse CO2 laser followed by topical ALA-PDT. PDT was repeated till complete response was achieved. Approximately half of the patients only needed one session of PDT treatment and another half needed multiple PDT treatments to achieve complete response. During the 6-month follow-up 7.1% of patients relapsed. In terms of complete response rate and recurrence rate there were no statistical differences between perianal and genital groups. No severe adverse effects were observed. CO2 laser vaporation plus ALA-PDT is a highly effective modality for treating CA.