Clinicopathological characteristics of fibrosing alopecia in a pattern distribution: a single-center, retrospective study.

BACKGROUND: Fibrosing alopecia in a pattern distribution (FAPD) is a distinct entity of primary cicatricial alopecia (PCA), mimicking diffuse hair loss of androgenetic alopecia (AGA) with trichoscopic and histopathologic features of both AGA and lichen planopilaris (LPP). METHODS: Clinical, demographic, and histopathological data of 20 FAPD patients were retrospectively collected. RESULTS: All patients presented with female pattern hair loss with a median Sinclair grade of 3. Trichoscopic findings revealed hair diameter variability (20/20), perifollicular erythema (mild 7/20, moderate 11/20, severe 2/20), peripilar casts (none 2/20, mild 12/20, moderate 5/20, severe 1/20), and loss of follicular ostia (+12/20, ±7/20, -1/20). Histopathologic examination revealed perifollicular lymphocytic infiltration at the infundibulum or isthmus level and an increase of vellus-like hairs. All cases showed interface dermatitis with concentric perifollicular lamellar fibrosis and follicular scars. Infundibular or isthmic infiltration of mast cells was found. CONCLUSIONS: The uniqueness of our study lies in perifollicular mast cells and discovering that the young population is at higher risk than previously thought. Clinicopathological features of FAPD were identified, filling the void of much-needed details for FAPD diagnosis tailored to the Chinese population.

Safety and efficacy of Pimecrolimus in atopic dermatitis among Chinese infants: a sub-group analysis of a five-year open-label study.

INTRODUCTION: Atopic dermatitis (AD) exhibits difference in immune polarization between Caucasians and Asian races due to which an evaluation of the efficacy and safety of Pimecrolimus (PIM) in Asian population is called for. The current study addresses the need via a sub-group analysis of the PETITE study (NCT00120523) to evaluate the safety and efficacy of PIM in Chinese infants. MATERIALS AND METHODS: Patients with AD (≥3 months-<12 months of age) were randomized in a 1:1 ratio to either PIM 1% cream or topical corticosteroids (TCS). The primary endpoint was safety. The secondary endpoint was efficacy. RESULTS: 120 patients were randomized to either PIM 1% or TCS (n = 61 for PIM, n = 59 for TCS). The most often reported adverse events were reported by similar proportions of patients treated with PIM or TCS. There was a progressive increase in overall IGA treatment success in infants treated with PIM (82.9%, p < .05, 95% CI: 70.4, 95.3) after 26 weeks which was comparable to the TCS group (88.5%, p < .05, 95% CI: 79.8, 97.1). CONCLUSION: PIM showed an early and sustained efficacy in the Chinese sub-population with a substantial corticosteroid-sparing effect in patients with AD.

Disrupted citric acid metabolism inhibits hair growth.

Hair follicles (HFs) play an essential role in sustaining a persistent hair growth cycle. The activities of dermal papilla cells (DPCs) and other cells inside the HFs dominate the process of hair growth. However, the detailed molecular mechanisms remain largely unknown. To investigate the role of citric acid (CA) metabolism in hair growth, we evaluated the effect of citrate synthase (CS)-CA axis on hair growth in vivo and in vitro. Mice hair growth was evaluated by morphology and histopathology analysis. The inflammation and apoptosis levels in mice, HFs, and DPCs were detected by immunohistofluorescence, qPCR, ELISA, western blot, and TUNEL assay. Cell proliferation, cell cycle, and cell apoptosis in DPCs were analyzed by real-time cell analysis and flow cytometer. We found that subcutaneous injection of CA in mice caused significant hair growth suppression, skin lesion, inflammatory response, cell apoptosis, and promotion of catagen entry, compared with the saline control, by activating p-p65 and apoptosis signaling in an NLRP3-dependent manner. In cultured human HFs, CA attenuated the hair shaft production and accelerated HF catagen entry by regulating the above-mentioned pathways. Additionally, CA hampered the proliferation rate of DPCs via inducing cell apoptosis and cell cycle arrest. Considering that citrate synthase (CS) is responsible for CA production and is a rate-limiting enzyme of the tricarboxylic acid cycle, we also investigated the role of CS in CA metabolism and hair growth. As expected, knockdown of CS reduced CA production and reversed CA-induced hair growth inhibition, anagen shrink, inflammation, and apoptosis both in HFs and DPCs. Our experiments demonstrated that CS-CA axis serves as an important mediator and might be a potential therapeutic target in hair growth.

Insights into male androgenetic alopecia using comparative transcriptome profiling: hypoxia-inducible factor-1 and Wnt/ß-catenin signalling pathways.

BACKGROUND: The key pathophysiological changes in androgenetic alopecia (AGA) are limited to hair follicles (HFs) in frontal and vertex regions, sparing the occipital region. OBJECTIVES: To identify biological differences among HF subpopulations. METHODS: Paired vertex and occipital HFs from 10 male donors with AGA were collected for RNA sequencing assay. Furthermore, HF and cell experiments were conducted on the identified key genes to reveal their roles in AGA. RESULTS: Transcriptome profiles revealed that 506 mRNAs, 55 microRNAs and 127 long noncoding RNAs were differentially expressed in the AGA vertex HFs. Pathway analysis of mRNAs and microRNAs revealed involvement of the hypoxia-inducible factor (HIF)-1, Wnt/ß-catenin, and focal adhesion pathways. Differential expression of HIF-1 prolyl hydroxylase enzymes (EGLN1, EGLN3) and Wnt/ß-catenin pathway inhibitors (SERPINF1, SFRP2) was experimentally validated. In vitro studies revealed that reduction of EGLN1, EGLN3, SERPINF1 and SFRP2 stimulated proliferation of dermal papilla cells. Ex vivo HF studies showed that downregulation of EGLN1, EGLN3 and SERPINF1 promoted HF growth, postponed HF catagen transition, and prolonged the anagen stage, suggesting that these genes may be potentially utilized as therapeutic targets for AGA. CONCLUSIONS: We characterized key transcriptome changes in male AGA HFs, and found that HIF-1 pathway-related genes (EGLN1, EGLN3) and Wnt pathway inhibitors (SERPINF1, SFRP2) may play important roles in AGA. What is already known about this topic? Multiple differentially expressed genes and signalling pathways have been found between hair follicles (HFs) in the balding area (frontal and vertex regions) and nonbalding area (occipital region) of individuals with androgenetic alopecia (AGA). A whole-transcriptome atlas of the vertex and occipital region is lacking. What does this study add? We identified a number of differentially expressed genes and pathways between balding vertex and nonbalding occipital AGA HFs by using whole-transcriptome analyses. We identified pathways not previously reported in AGA, such as the hypoxia-inducible factor (HIF)-1 signalling pathway. We verified that HIF-1 pathway-related genes (EGLN1, EGLN3) and Wnt pathway inhibitors (PEDF, SFRP2) played important roles in dermal papilla cell activity, hair growth and the hair cycle. What is the translational message? The EGLN1, EGLN3, SERPINF1 and SFRP2 genes may be potentially utilized as therapeutic targets for AGA.

Hair Growth-Promoting Effect of Resveratrol in Mice, Human Hair Follicles and Dermal Papilla Cells.

BACKGROUND: Oxidative damage has been found in various types of hair loss. As a polyphenolic phytoalexin, resveratrol (RSV) is known as an antioxidant, anti-inflammatory and anti-apoptotic agent. OBJECTIVE: Thus, we aim to examine the effects of RSV on hair growth. METHODS: In vivo C57BL/6 mice were used to evaluate the effects of RSV on hair cycle, hair length, skin thickness, hair follicle diameter, hair cycle score and the percentage of hair cycle stage. Then hair shaft length and hair cycle were evaluated by human hair follicles (HFs) ex vivo. The proliferative activities of human dermal papilla cells (hDPCs) cultured in vitro with RSV were assessed using RTCA. The ability of RSV to protect hDPCs against H2O2-induced oxidative damage is examined by a ROS assay kit. RESULTS: Topical application of RSV significantly promoted hair growth and stimulated the transition of hair cycle from telogen into the anagen phase on shaved C57BL/6 mice. Ex vivo experiments showed that RSV increased the hair shaft length of HFs and delayed the entry into catagen. In vitro experiments indicated that RSV proliferated hDPCs and prevented hDPCs from oxidative damage caused by H2O2. CONCLUSION: RSV can promote hair growth and may be a potential candidate for the treatment of hair loss.

Fine Particulate Matter (PM2.5) is a Risk Factor for Dermatitis by Promoting the Expression of Thymic Stromal Lymphopoietin (TSLP) in Keratinocytes.

AIM: Common indoor pollutants, as fine particulate matter (PM2.5), can damage people's health and cause skin allergies. However, it remains unknown which common pollutants can lead to allergy, such as, in children atopic dermatitis, and what is the key molecule. This study aimed to investigate the thymic stromal lymphopoietin (TSLP) produced from keratinocytes after environmental pollutant stimulation. METHODS: PAM212 cells were treated by several pollutants, including PM2.5, formaldehyde, m-xylene, and 1,2,4-trimethylbenzene, and tried to analyze their relationships. The mRNA expression level of TSLP was determined by qPCR. The protein level of TSLP was detected by ELISA analysis. RESULTS: The mRNA expression of TSLP was significantly up-regulated when PAM212 cells were stimulated by PM2.5 at 25 µg/ml for 12 h. Meanwhile, the protein level of TSLP in culture supernatant was increased. However, TSLP protein production was not detected in culture supernatant treated with formaldehyde, m-xylene, and 1, 2, 4-trimethylbenzene. CONCLUSION: PM2.5 promotes the expression of TSLP and may aggravate allergic response using this pathway.

Sublingual immunotherapy of atopic dermatitis in mite-sensitized patients: a multi-centre, randomized, double-blind, placebo-controlled study.

Allergen-specific immunotherapy is widely used for allergic rhinitis and asthma treatment worldwide. This study explored the efficacy and safety of sublingual immunotherapy (SLIT) with the extracts of Dermatophagoides Farinae (D. farinae Drops) on house dust mites (HDM)-induced atopic dermatitis (AD). 239 patients with HDM-induced AD were recruited and exposure to a multi-centre, randomized, double-blind, and placebo-controlled clinical trials for 36 weeks, which were randomly divided into placebo and sublingual D. farinae Drops groups (high-dose, medium-dose and low-dose), respectively. Statistical analysis was performed in three groups: Full Analysis Set, Per Protocol Set and Safety Set. 48 cases have withdrawn from the study before the end of study. As primary outcomes, significant decreases in scoring atopic dermatitis and total medication score were showed in medium-dose and high-dose D. farinae Drops groups. In the sixth visit, the skin lesion area showed a statistically significant difference between high-dose/medium-dose D. farinae Drops group and placebo group (p < .05). Most adverse events are slight, and no life-threatening adverse drug reaction happened. Our research demonstrates the beneficial effect of SLIT with high or medium dose D. farinae Drops on AD, and the treatment was well tolerated.

IKULDAS: An Improved kNN-Based UHF RFID Indoor Localization Algorithm for Directional Radiation Scenario.

Ultra high frequency radio frequency identification (UHF RFID)-based indoor localization technology has been a competitive candidate for context-awareness services. Previous works mainly utilize a simplified Friis transmission equation for simulating/rectifying received signal strength indicator (RSSI) values, in which the directional radiation of tag antenna and reader antenna was not fully considered, leading to unfavorable performance degradation. Moreover, a k-nearest neighbor (kNN) algorithm is widely used in existing systems, whereas the selection of an appropriate k value remains a critical issue. To solve such problems, this paper presents an improved kNN-based indoor localization algorithm for a directional radiation scenario, IKULDAS. Based on the gain features of dipole antenna and patch antenna, a novel RSSI estimation model is first established. By introducing the inclination angle and rotation angle to characterize the antenna postures, the gains of tag antenna and reader antenna referring to direct path and reflection paths are re-expressed. Then, three strategies are proposed and embedded into typical kNN for improving the localization performance. In IKULDAS, the optimal single fixed rotation angle is introduced for filtering a superior measurement and an NJW-based algorithm is advised for extracting nearest-neighbor reference tags. Furthermore, a dynamic mapping mechanism is proposed to accelerate the tracking process. Simulation results show that IKULDAS achieves a higher positioning accuracy and lower time consumption compared to other typical algorithms.

Autophagy deficient melanocytes display a senescence associated secretory phenotype that includes oxidized lipid mediators.

Autophagy is a recycling program which allows cells to adapt to metabolic needs and to stress. Defects in autophagy can affect metabolism, aging, proteostasis and inflammation. Autophagy pathway genes, including autophagy related 7 (Atg7), have been associated with the regulation of skin pigmentation, and autophagy defects disturb the biogenesis and transport of melanosomes in melanocytes as well as transfer and processing of melanin into keratinocytes. We have previously shown that mice whose melanocytes or keratinocytes lack Atg7 (and thus autophagy) as a result of specific gene knockout still retained functioning melanosome synthesis and transfer, and displayed only moderate reduction of pigmentation. In cell culture the Atg7 deficient melanocytes were prone to premature senescence and dysregulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling. To elucidate the biochemical basis of this phenotype, we performed a study on global gene expression, protein secretion and phospholipid composition in Atg7 deficient versus Atg7 expressing melanocytes. In cell culture Atg7 deficient melanocytes showed a pro-inflammatory gene expression signature and secreted higher levels of C-X-C motif chemokine ligand -1,-2,-10 and -12 (Cxcl1, Cxcl2, Cxcl10, Cxcl12), which are implicated in the pathogenesis of pigmentary disorders and expressed higher amounts of matrix metalloproteinases -3 and -13 (Mmp3, Mmp13). The analysis of membrane phospholipid composition identified an increase in the arachidonic- to linoleic acid ratio in the autophagy deficient cells, as well as an increase in oxidized phospholipid species that act as danger associated molecular patterns (DAMPs). The secretion of inflammation related factors suggests that autophagy deficient melanocytes display a senescence associated secretory phenotype (SASP), and we propose oxidized lipid mediators as novel components of this SASP.

Suppression of autophagy dysregulates the antioxidant response and causes premature senescence of melanocytes.

Autophagy is the central cellular mechanism for delivering organelles and cytoplasm to lysosomes for degradation and recycling of their molecular components. To determine the contribution of autophagy to melanocyte (MC) biology, we inactivated the essential autophagy gene Atg7 specifically in MCs using the Cre-loxP system. This gene deletion efficiently suppressed a key step in autophagy, lipidation of microtubule-associated protein 1 light chain 3 beta (LC3), in MCs and induced slight hypopigmentation of the epidermis in mice. The melanin content of hair was decreased by 10-15% in mice with autophagy-deficient MC as compared with control animals. When cultured in vitro, MCs from mutant and control mice produced equal amounts of melanin per cell. However, Atg7-deficient MCs entered into premature growth arrest and accumulated reactive oxygen species (ROS) damage, ubiquitinated proteins, and the multi-functional adapter protein SQSTM1/p62. Moreover, nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent expression of NAD(P)H dehydrogenase, quinone 1, and glutathione S-transferase Mu 1 was increased, indicating a contribution of autophagy to redox homeostasis in MCs. In summary, the results of our study suggest that Atg7-dependent autophagy is dispensable for melanogenesis but necessary for achieving the full proliferative capacity of MCs.

Retrospective study of photopatch testing in a Chinese population during a 7-year period.

BACKGROUND: Photoallergic contact dermatitis (PACD) is of importance in a proportion of photodermatoses and can be evaluated through photopatch testing (PPT). OBJECTIVES: The objectives of this study were to evaluate the results of PPT and investigate the prevalence of PACD reactions to different photoallergens in Chinese patients at the Department of Dermatology of Huashan Hospital Fudan University during a 7-year period. METHODS: A retrospective PPT study was conducted. During the 7 years, 4957 patients attending for investigation of suspected photodermatoses were tested according to the European consensus methodology with up to 14 allergens prepared according to Chinese National Standards. The reactions were scored using the International Contact Dermatitis Research Group visual scoring system. RESULTS: A total of 3472 PACD reactions in 2454 subjects (49.5%) were recorded. The most common agents were chlorpromazine (44.3%), followed by para-aminobenzoic acid (14.7%), thimerosal (8.9%), and sulfanilamide (6.9%). Allergic contact dermatitis reactions comprised 409 reactions in 399 subjects (8%). Photoinhibition and photoaugmentation of allergic contact dermatitis compromised 3810 reactions in 2412 subjects and 11 reactions in 11 subjects, respectively. Irritant reactions (1928 reactions) were seen in 1140 subjects. CONCLUSIONS: The most predominant photoallergens in our region were chlorpromazine, para-aminobenzoic acid, thimerosal, and sulfanilamide, which likely reflected the particular exposures of this Chinese population.

Contact sensitization in Chinese patients with hand eczema.

BACKGROUND: Contact sensitization is an important cause of hand eczema, a common disease that affects both daily and occupational life. OBJECTIVE: To describe contact allergens in Chinese patients with hand eczema and to analyze the association between allergens and occupational exposure. METHODS: Three hundred sixty-six patients with hand eczema underwent patch testing with a modified North American standard series between September 1989 and December 2009. RESULTS: Positive patch-test reactions were observed in 74% of patients. The most frequent allergens were p-phenylenediamine (22.7%), nickel sulfate (21.9%), fragrance mix (19.9%), ammoniated mercury (19.7%), and carba mix (17.8%). Nickel and fragrance allergy in women, and carba mix and chromate allergy in men, showed gender predilection, and 64.2% of patients developed hand eczema from occupational exposure. Positive reactions to p-phenylenediamine in hairdressers and to chromate in metalworkers and construction workers presented higher frequencies (p < .05). CONCLUSIONS: p-Phenylenediamine, nickel, fragrance, mercury, and rubber chemicals are common allergens in Chinese patients with hand eczema. Gender and occupation may cause different exposures; thus, allergens may vary.

Prevalence of contact allergy at a dermatology clinic in China from 1990-2009.

BACKGROUND: The prevalence of contact allergy varies in different regions and populations. OBJECTIVE: To describe the frequency of sensitization in patients with dermatitis or eczema referred to Peking University First Hospital and analyze the trends in the prevalence of common allergens from January 1, 1990, to December 31, 2009. METHODS: A total of 1,858 patients were patch tested with the Chinese baseline series of contact allergens. Data were collected from retrospective charts and analyzed. RESULTS: Positive reactions to one or more allergens were shown in 1,374 patients (74.0%). The most common sensitizers were nickel sulfate (25.7%), fragrance mix I (25.6%), thiuram mix (25.5%), ammoniated mercury (20.5%), and p-phenylenediamine (19.1%). A statistically significant increase of sensitization over the 20-year period was seen for nickel sulfate, fragrance mix, ammoniated mercury, colophony, ethylenediamine, and potassium dichromate. Mercapto mix showed a trend of a statistically significant decrease in sensitizations from 1990 to 2009. CONCLUSIONS: The patterns of contact allergy in patients from Peking University Hospital are different from those of patients in other regions of China, in European countries, and in the United States. Nickel and fragrance mix were the most common allergens, and the sensitization rates of these two allergens had been increasing remarkably during the 20 years from 1990 to 2009.