Treatment With Selumetinib for Café-au-Lait Macules and Plexiform Neurofibroma in Pediatric Patients With Neurofibromatosis Type 1.

This case report describes 4 patients with a rare autosomal dominant multisystem disorder resulting from NF1 variants that leads to café-au-lait macules and neurofibromas.

The Role of Mesenchymal Stem Cells in Hair Regeneration and Hair Cycle.

The health of hair is directly related to people's health and appearance. Hair has key physiological functions, including skin protection and temperature regulation. Hair follicle (HF) is a vital mini-organ that directly impacts hair growth. Besides, various signaling pathways and molecules regulate the growth cycle transition of HFs. Hair and its regeneration studies have attracted much interest in recent years with the increasing rate of alopecia. Mesenchymal stem cells (MSCs), as pluripotent stem cells, can differentiate into fat, bone, and cartilage and stimulate regeneration and immunological regulation. MSCs have been widely employed to treat various clinical diseases, such as bone and cartilage injury, nerve injury, and lung injury. Besides, MSCs can be used for treatment of hair diseases due to their regenerative and immunomodulatory abilities. This review aimed to assess MSCs' treatment for alopecia, pertinent signaling pathways, and new material for hair regeneration in the last 5 years.

TMT-Based Quantitative Proteomic Analysis Reveals the Effect of Bone Marrow Derived Mesenchymal Stem Cell on Hair Follicle Regeneration.

Hair loss (HL) is a common chronic problem of poorly defined etiology. Herein, we explored the functionality of bone marrow-derived mesenchymal stem cell (BMSC) and conditioned medium (MSC-CM) as regulators of hair follicle proliferation and regeneration, and the mechanistic basis for such activity. BMSC were cultured and identified in vitro through the induction of multilineage differentiation and the use of a CCK-8 kit. The dorsal skin of mice was then injected with BMSC and MSC-CM, and the impact of these injections on hair cycle transition and hair follicle stem cell (HFSC) proliferation was then evaluated via hematoxylin and eosin (H&E) staining and immunofluorescent (IF) staining. We then conducted a tandem mass tags (TMT)-based quantitative proteomic analysis of control mice and mice treated with BMSC or MSC-CM to identify differentially expressed proteins (DEPs) associated with these treatments. Parallel reaction monitoring (PRM) was utilized as a means of verifying our proteomic analysis results. Herein, we found that BMSC and MSC-CM injection resulted in the transition of telogen hair follicles to anagen hair follicles, and we observed the enhanced proliferation of HFSCs positive for Krt15 and Sox9. Our TMT analyses identified 1,060 and 770 DEPs (fold change＞1.2 or＜0.83 and p ＜ 0.05) when comparing the BMSC vs. control and MSC-CM vs. control groups, respectively. Subsequent PRM validation of 14 selected DEPs confirmed these findings, and led to the identification of Stmn1, Ncapd2, Krt25, and Ctps1 as hub DEPs in a protein-protein interaction network. Together, these data suggest that BMSC and MSC-CM treatment can promote the proliferation of HFSCs, thereby facilitating hair follicle regeneration. Our proteomics analyses further indicate that Krt25, Cpm, Stmn1, and Mb may play central roles in hair follicle transition in this context and may represent viable clinical targets for the treatment of HL.

Randomized trial of electrodynamic microneedle combined with 5% minoxidil topical solution for the treatment of Chinese male Androgenetic alopecia.

Background: In treating androgenetic alopecia, 5% minoxidil is a commonly used topical drug. By using electrodynamic microneedle at the same time may increase absorption of minoxidil and further stimulate hair growth.Objective: A 24-week, randomized, evaluator blinded, comparative study was performed to evaluate the efficacy of treating Chinese male androgenetic alopecia using microneedle combined with 5% minoxidil topical solution. Methods: Randomized subjects received topical 5% minoxidil (group 1, n = 20), local electrodynamic microneedle treatments (group 2, n = 20), or local electrodynamic microneedle treatments plus topical 5% minoxidil (group 3, n = 20). A total of 12 microneedle treatments were performed every 2 weeks with 2ml 5% minoxidil delivery in group three during each microneedle treatment. Patient receiving topical 5% minoxidil applied 1 ml of the solution twice daily over the course of the study. A total of 60 Chinese male subjects with Norwood-Hamilton type III-VI androgenetic alopecia were treated.Results: The mean improvement in total hair density from baseline to 24 weeks was 18.8/cm2 in group 1, 23.4/cm2 in group 2, and 38.3/cm2 in group 3. The hair growth in the three groups was significantly different (P = 0.002), but there were no significant differences in toxicity found between the three groups.Conclusions: Treatment with microneedle plus topical 5% minoxidil was associated with the best hair growth.

Resibufogenin suppresses tumor growth and inhibits glycolysis in ovarian cancer by modulating PIM1.

Ovarian cancer is a common human malignancy of the female reproductive system. However, chemotherapy has been proven to have limited effectiveness in a majority of patients. Resibufogenin (RB) is a major active ingredient in cinobufacini, which has been used in the treatment of human malignancies as adjunct agents. This study was designed to examine the anti-cancer effect of RB and the underlying mechanisms in ovarian cancer. Our results showed that RB treatment resulted in cell death, cell cycle arrest, and apoptosis in ovarian cancer cells. The anti-growth and pro-apoptotic effects of RB were also validated in xenograft mice models. Proteomics analysis indicated that RB was able to alter the expressions of several genes, which were involved in the regulation of glycolysis. The suppression effect of RB in the glycolysis pathway of ovarian cancer cells was validated by decreased glucose consumption, lactate production, and extracellular acidification rate (ECAR). We proposed that PIM1 functioned as the key target that mediated the anti-cancer effect of RB against ovarian cancer cells. Our results have revealed that RB downregulated PIM1 in ovarian cancer cells and its downstream genes involved in glycolysis. Moreover, our results indicated that the anti-growth activities and suppressing effect of RB on glycolysis were enhanced significantly by PIM1 knockdown but was attenuated by ectopic PIM1 expression. This provided evidence to support the role of PIM1 in the anti-cancer activities of RB.

Embryonic-like regenerative phenomenon: wound-induced hair follicle neogenesis.

Wound-induced hair follicle neogenesis (WIHN) is a regenerative phenomenon that occurs widely in the skin of adult mammalians. A fully functional follicle can regenerate in the center of a full-thickness wound with a large enough size. The cellular origin of this process is similar to embryonic process. Many growth and development-related pathways are involved in WIHN. Studying WIHN can deeply explore the mechanism of biological growth, development and regeneration, and can identify new treatments for hair-related disorders. Our review aims to enlighten future study by summarizing the clinical manifestation of WIHN, as well as the cellular and molecular mechanism of WIHN in recent studies.

Prostanoids and Hair Follicles: Implications for Therapy of Hair Disorders.

Prostanoids, including prostaglandins (PGs) and thromboxane A2 (TXA2), are a family of lipid-derived autacoids that modulate many physiological systems and pathological contexts. Prostanoids are generated by sequential metabolism of arachidonic acid, catalysed by cyclo-oxygenase, to PGH2, which is then converted to PGD2, PGE2, PGF2α, PGI2 and TXA2, catalysed by their specific synthases. Recent evidence suggests that prostanoids play a role in regulating hair growth. The PGF2α analogue is Food and Drug Administration-approved in the US and routinely used to enhance the growth of human eyelashes. PGE2 is reported to protect from radiation-induced hair loss in mice. Conversely, PGD2 inhibits hair growth. This paper reviews the metabolism of prostanoids and the expression pattern of prostanoid receptors in hair follicles, focussing on their different and opposing effects on hair growth and the underlying mechanisms. This has potential clinical relevance in the treatment and prevention of hair disorders.

A Split-Face Study of Dual-Wavelength Laser on Neck and Facial Port-Wine Stains in Chinese Patients.

BACKGROUND: Although pulsed dye laser (PDL) has long been regarded as the gold standard in treating port-wine stain (PWS), advanced PWS with deeper coloration may display resistance because of limited penetration depth of 585 or 595-nm light. Recently, a dual-wavelength laser system has been reported to achieve pronounced fading in many patients. OBJECTIVE: The objective was to evaluate the efficacy and safety of a dual-wavelength laser device in treatment of neck and facial PWS in a direct side-by-side comparison. METHODS: Sixteen Chinese patients with neck and/or facial PWSs were enrolled in the study. All lesions were randomly divided into two area, treated area and adjacent untreated area. Five successive treatments using a dual-wavelength laser system (595-nm PDL combined with 1,064-nm Nd:YAG laser) were delivered on treated areas at 4- to 6-week intervals. The adjacent area was not treated as self control. Two blinded dermatologists evaluated the clinical changes by comparing the before and after photos. Erythema index (EI) values were measured with a non-invasive instrument. RESULTS: After five sessions of treatment, over 62.5% (10/16) patients achieved more than 50% (moderate or significant) improvement. The efficacy maintained at the 3-month follow-up visit. The values of EI on treated area showed a significant decrease. Adverse effects of treated area were limited. CONCLUSION: Using this split-face module, the dual-wavelength laser system is proved to be effective and well tolerated in treating neck and facial PWSs in Chinese patients. Adverse effects were minimal and acceptable.

Endostatin inhibits the tumorigenesis of hemangioendothelioma via downregulation of CXCL1.

Hemangioendotheliomas could be repressed by various anti-angiogenic agents in animal models. It was unclear whether the agents target hemangioendothelioma cells directly. This study elucidated the mechanism by which endostatin inhibited hemangioendothelioma progression. Expression of the endostatin receptors nucleolin and integrin α5ß1 in hemangioendothelioma was assessed by immunohistochemistry. The effects of endostatin on the hemangioendothelioma-derived cells (EOMA) were evaluated by proliferation and apoptosis assays and by angiogenesis array screening. This revealed the contribution of the Chemokine (C-X-C motif) ligand 1 (CXCL1) to hemangioendothelioma progression, which was explored in vitro and in vivo. The clinical relevance of CXCL1 expression in hemangioendothelioma was also evaluated using tissue array. EOMA cells expressed nucleolin and integrin α5ß1 and bound to endostatin. Endostatin did not alter proliferation or hypoxia-induced apoptosis in EOMA cells but it did impair the pro-angiogenic capacity of the cells. Endothelial cell migration was induced by CXCL1 produced by EOMA cells and endostatin downregulated CXCL1 production by inactivating its transcriptional factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). In vivo, the knockdown of CXCL1 significantly impaired EOMA cell growth in nude mice; endostatin had no effect when CXCL1 was overexpressed. A strong correlation was observed between CXCL1 levels and hemangioendothelioma occurrence in patients. CXCL1, which was responsible for hemangioendothelioma progression by stimulating angiogenesis, was impaired by endostatin via inactivation of NF-κB in an animal model. In vascular lesions in patients, CXCL1 expression was a negative prognostic factor. CXCL1-inhibting agents such as endostatin may constitute a useful approach to treat the malignant or intermediate vascular lesions.

Shikonin suppresses IL-17-induced VEGF expression via blockage of JAK2/STAT3 pathway.

IL-17 signaling in keratinocytes plays an important role in psoriasis, which is a benign, chronic skin disease characterized by keratinocytes hyperproliferation and increased dermal vascularity. Shikonin, isolated from the traditional medical herbs Lithospermum erythrorhizon, has long been found to possess different medicinal properties such as antibacterial, improving wound healing, anti-inflammatory and anti-tumor effects. However, the effects and mechanisms of shikonin on VEGF expression in keratinocytes mediated by IL-17 signaling, are still not fully clarified. In the present study, we investigated the effects and regulatory mechanisms of shikonin on VEGF expression in keratinocytes induced by IL-17 by in vitro and in vivo experiments. Our results showed that shikonin significantly inhibited IL-17-induced VEGF mRNA and protein expression in HaCaT cells and the secretion of VEGF by HaCaT cells, inhibited IL-17-induced IL-17R, pJAK2 and pSTAT3 expression, while up-regulated the expression of SOCS1 in HaCaT cells. Additionally, shikonin effectively suppressed VEGF expression in the skin of IL-17 stimulated mice. Furthermore, shikonin suppressed VEGF-induced tube formation of HUVECs and CD34 expression in the skin of IL-17 stimulated mice. These results imply that shikonin suppresses IL-17-induced VEGF expression in vitro and in vivo and the mechanisms may be related to its effect in blockage of JAK2/STAT3 pathway. These data deepen our understanding of shikonin in the inhibition of angiogenesis in inflammatory skin diseases such as psoriasis.

Protective effects of a topical antioxidant complex containing vitamins C and E and ferulic acid against ultraviolet irradiation-induced photodamage in Chinese women.

OBJECTIVE: The objective of the study was to investigate whether a topical antioxidant complex containing vitamins C and E and ferulic acid can protect solar-simulated ultraviolet irradiation (ssUVR)-induced acute photodamage in human skin. METHOD: Twelve healthy female Chinese subjects were enrolled in this study. Four unexposed sites on dorsal skin were marked for the experiment. The products containing antioxidant complex and vehicle were applied onto 2 sites, respectively, for 4 consecutive days. On day 4, the antioxidant complex-treated site, the vehicle-treated site, and the untreated site (positive control) received ssUVR (5 times the minimal erythema dose). The fourth site (negative control) received neither ssUVR nor treatment. Digital photographs were taken, and skin color was measured pre- and postirradiation. Skin biopsies were obtained 24 hours after exposure to ssUVR, for hematoxylin and eosin and immunohistochemical staining. RESULTS: A single, 5 times the minimal erythema dose of ssUVR substantially induced large amounts of sunburn cell formation, thymine dimer formation, overexpression of p53 protein, and depletion of CD1a+ Langerhans cells. The antioxidant complex containing vitamins C and E and ferulic acid conferred significant protection against biological events compared with other irradiated sites. CONCLUSION: A topical antioxidant complex containing vitamins C and E and ferulic acid has potential photoprotective effects against ssUVR-induced acute photodamage in human skin.

Ultrapulse-mode versus superpulse-mode fractional carbon dioxide laser on normal back skin.

BACKGROUND AND OBJECTIVES: Ultrapulse-mode (UPCO2) and superpulse-mode (SPCO2) fractional carbon dioxide lasers have been widely used to treat photo-aged skin, acne scars, and other skin conditions. This study was designed to compare the efficacy of new SPCO2 and UPCO2 lasers. MATERIALS AND METHODS: Seven healthy Chinese women received one pass of UPCO2 treatment on the left back and SPCO2 treatment on the right back. Pulse energies were 15 mJ at a density of 5%. Clinical outcomes and side effects were evaluated. Dermatoscope, in vivo reflectance confocal microscopy (RCM), and high-frequency ultrasonic equipment were used to observe skin responses noninvasively. Biopsies were taken for histologic evaluation. RESULTS: There was no significant difference between the two sides with regard to pain, edema, crust formation, erythema, or pigmentation. Histopathology showed that SPCO2 treatment could penetrate as deep as UPCO2. The two modes have similar efficacy in stimulating the synthesis and remodeling of collagen and elastin according to hematoxylin and eosin and Verhoeff-iron-hematoxylin stains, and the ultrasonography images showed a remarkable increase in skin thickness and density on both sides. CONCLUSION: There is no significant difference between UPCO2 and SPCO2 treatment on back skin in clinical side effects, histologic findings, RCM, or ultrasonographic observation.

Treatment of neck port-wine stain with intense pulsed light in Chinese population.

BACKGROUND: Studies of lasers or intense pulsed light (IPL) on facial port wine stain (PWS) were frequently reported. Neck PWS was seldom concerned. OBJECTIVE: This paper was aimed to identify the efficacy and safety of IPL in the treatment of neck PWS in Chinese patients. METHODS: Twenty-nine Chinese patients with neck PWS were enrolled to receive IPL therapy for five sessions at an interval of 4- to 5 weeks. The parameters were set as cut-off filters of 560 nm, single pulse with pulse width of 6 ms and fluence of 20-24 J/cm(2) or double pulse with pulse width of 4.5-5.0 ms, pulse delay of 15-30 ms, and fluence of 18-25 J/cm(2). The efficacy was evaluated using subjective assessment and non-invasive measurement. The adverse effects were recorded. RESULTS: Over 60% patients achieved more than 50% improvement and over 50% participants were very satisfied or satisfied with the treatment. The participants less than 18 years old achieved better efficacy than the participants over 18 years old. The red or purple lesions gained better response to IPL treatment than the pink lesions. Adverse effects were limited. CONCLUSION: IPL is effective in neck PWS of Chinese population. Adverse effects were minimal and acceptable.

Kanglaite attenuates UVB-induced down-regulation of aquaporin-3 in cultured human skin keratinocytes.

Ultraviolet (UV) radiation plays an important role in the pathogenesis of skin photoaging. Depending on the wavelength of UV, the epidermis is affected primarily by UVB. One major characteristic of photoaging is the dehydration of the skin. Membrane-inserted water channels (aquaporins) are involved in this process. In this study we demonstrated that UVB radiation induced aquaporin-3 (AQP3) down-regulation in cultured human skin keratinocytes. Kanglaite is a mixture consisting of extractions of Coix Seed, which is an effective anti-neoplastic agent and can inhibit the activities of protein kinase C and NF-κB. We demonstrated that Kanglaite inhibited UVB-induced AQP3 down-regulation of cultured human skin keratinocytes. Our findings provide a potential new agent for anti-photoaging. The related molecular mechanisms remain to be further elucidated.