Exploring the role of growth factors as potential regulators in psoriatic plaque formation.

Psoriasis is a chronic inflammatory skin disease in which growth activity is more prominent than inflammatory activity at the centre of lesional skin (CE skin). This growth activity is partly influenced by growth factors (GFs) that play an important role in cell growth and inflammation during the plaque development. In this study, we identified potential GFs in CE skin and predicted their regulatory functions and biological activity in mediating transcripts in the plaques. Samples of uninvolved skin (UN skin) and CE skin were biopsied from patients with psoriasis vulgaris for RNA-sequencing analysis in order to identify differentially expressed genes (DEGs). Our finding revealed that epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF) and hepatocyte growth factor (HGF) signalling were enriched by CE/UN skin-derived DEGs. Additionally, several EGFR ligands, namely EGF, heparin-binding EGF like growth factor (HB-EGF), amphiregulin (AREG) and transforming growth factor (TGF)-α, as well as TGF-ß1, TGF-ß2, vascular endothelial growth factor-A, FGFs, PDGF-B and HGF, were predicted to be GF regulators. The regulatory pattern and biological activity of these GF regulators on mediating the CE/UN skin-derived DEGs was demonstrated. This study provides a novel hypothesis regarding the overall regulatory function of GFs, which appear to modulate the expression of the transcripts involved in inflammation and growth in the CE skin. In addition, some GFs may exert anti-inflammatory effects. Further investigations on the mechanisms underlying this regulation may contribute to a deeper understanding of psoriasis and the identification of potential therapeutic targets for patients with psoriasis.

Elucidating the NB-UVB mechanism by comparing transcriptome alteration on the edge and center of psoriatic plaques.

Narrow band-ultraviolet B (NB-UVB) is an effective treatment for psoriasis. We aim to generate a potential mechanism of NB-UVB through comparing the transcriptomic profile before and after NB-UVB treatment between the peripheral edge of lesional skin (PE skin) and the center of lesional skin (CE skin) on the basis of molecular mechanisms of these two areas display different downstream functions. More than one-fourth of the NB-UVB-altered genes were found to be plaque-specific. Some of them were psoriasis signature genes that were downregulated by NB-UVB in, both, PE and CE skin (core alteration), such as IL36G, DEFB4A/B, S100A15, KRT16, and KRT6A. After NB-UVB treatment, the activity score of upstream cytokines, such as interferons, interleukin (IL)-6, IL-17, and IL-22 in pathogenesis decreased. In addition, NB-UVB could restore normal keratinization by upregulating LORICRIN and KRT2, particularly in the CE skin. Finally, we illustrated that NB-UVB is capable of suppressing molecules from the initiation to maintenance phase of plaque formation, thereby normalizing psoriatic plaques. This finding supports the usefulness of NB-UVB treatment in clinical practice and may help in the development of new treatment approaches in which NB-UVB treatment is included for patients with psoriasis or other inflammatory skin diseases.

The efficacy of LED microneedle patch on hair growth in mice.

Light penetration depth in the scalp is a key limitation of low-level light therapy for the treatment of androgenetic alopecia (AGA). A novel light emitting diode (LED) microneedle patch was designed to achieve greater efficacy by enhancing the percutaneous light delivery. The study aimed to investigate the efficacy and safety of this device on hair growth in mice. Thirty-five male C57BL/6 mice which their dorsal skin was split into upper and lower parts to receive either LED irradiation alone or LED irradiation with a microneedle patch. Red (629 nm), green (513 nm), and blue light (465 nm) at an energy dose of 0.2 J/cm2 were applied once daily for 28 days. Outcomes were evaluated weekly using digital photographs. Histopathological findings were assessed using a 6 mm punch biopsy. A significant increase in hair growth was observed in the green light, moderate in the red light, and the lowest in the blue light group. The addition of the microneedle patch to LED irradiation enhanced greater and faster anagen entry in all the groups. Histopathology showed an apparent increase in the number of hair follicles, collagen bundles in the dermis, angiogenesis, and mononuclear cell infiltration after treatment with the green-light LED microneedle patches. No serious adverse effects were observed during the experiment. Our study provides evidence that the newly developed green-light LED microneedle patch caused the optimal telogen-to-anagen transition and could lead to new approaches for AGA. Microneedle stimulation may aid percutaneous light delivery to the target hair follicle stem cells.

Comparison of transcriptomic profiles in edge to center of plaque reveals chronological molecular events in psoriatic plaque formation.

BACKGROUND: Peripheral edge (PE) of plaques contains inflammatory molecules and has potential to initiate plaque formation, while the center (CE) of plaques has regression trends. OBJECTIVE: To elucidate the chronological molecular events by comparing the gene profiles in PE skin to those in CE skin. METHODS: Biopsied PE, CE, and uninvolved (UN) skin samples were analyzed by next-generation sequencing. Three groups of differentially expressed genes (DEGs) were analyzed, PE/UN-, CE/UN-, and PE/CE-skin-derived DEGs. RESULTS: PE skin contained inflammation-priming molecules, such as S100A7 and S100A15, and inflammatory drivers, such as interleukin (IL)-36α. IL-6 signaling was more active in PE than in CE skin. IL-8, S100A7, S100A8, S100A9, and human ß-defensin-2 were all regulated with the similar pattern in both areas. However, PE skin created a more active inflammatory network and downstream functions, including chemotaxis and angiogenesis, were more prominent than in CE skin. Conversely, CE skin, where epidermal growth factor and hepatocyte growth factor increased their activity, was found to be more stable. CONCLUSION: This is the first RNA-seq-based report to determine the chronological molecular events in plaque formation. In the early phase, inflammation might be initiated through molecules, such as IL-36α, S100A7, and S100A15, as observed in PE skin. The inflammation state in PE skin progresses to the more stable state found in CE skin. In CE skin, the growth factor activities are increased, which might lead to attenuation of initial inflammation and initiation of the regression phase. These molecular events may accelerate research towards developing novel therapies for psoriasis.

Skin Microbiota Profiles from Tape Stripping and Skin Biopsy Samples of Patients with Psoriasis Treated with Narrowband Ultraviolet B.

Purpose: Although the pathogenesis of psoriasis involves the dermis, most previous studies collected samples using the swab technique. A recent study examining the microbiomes obtained via both skin biopsies and swabs revealed a significant difference in normal skin. We hypothesized that the microbiome profile of patients with psoriasis from tape stripping and skin biopsy might be different. This study sought to contribute to microbiome research on psoriasis by investigating the changes in the microbiome during narrowband ultraviolet B (NBUVB) therapy by comparing the results from the different sampling techniques of tape stripping and skin biopsy. Patients and Methods: Twenty-three participants, including 14 patients with chronic plaque psoriasis and nine healthy controls, were recruited, and nine patients with psoriasis completed 20-sessions of NBUVB treatment. Skin microbiota from both techniques was analyzed using the 16S rRNA gene at baseline and after treatment. Results: A clear difference was observed between the results from the two sampling techniques. Alpha diversity of the microbiota obtained from tape stripping was higher than that of the microbiota from skin biopsy, whereas beta diversity was clustered into two groups by sampling technique. The microbiome was altered during NBUVB treatment using both sampling techniques. Conclusion: Different sampling techniques resulted in different microbiome profiles in patients with psoriasis. Tape stripping and swabs are feasible procedures and are mostly used in psoriasis and other skin microbiome studies; however, skin biopsy may also expand our understanding of psoriasis and other skin diseases that pathophysiology involves deeper to the dermis or subcutaneous tissue.

Efficacy of a novel microneedle patch for rejuvenation of the nasolabial fold.

BACKGROUND: Skin rejuvenation plays a significant role in the esthetic medicine market. Microneedle patches have been developed for a wide range of applications based on the principles of transdermal drug delivery; however, clinical trials of microneedle patches for skin rejuvenation remain limited. AIMS: This study was conducted to examine the efficacy of microneedle patches for improving nasolabial folds. METHODS: A total of 23 Thai women completed this prospective clinical trial. The participants were treated according to a split-face design, with application of microneedle patch plus 1.8% hyaluronic acid solution to the right nasolabial fold and microneedle patch alone to the left nasolabial fold. The treatments were applied to the nasolabial fold for 8 weeks. The test areas were measured before treatment and at 2, 4, 8, 12, and 16 weeks after the use of the test product. RESULTS: Combination treatment using the microneedle patch plus hyaluronic acid solution and use of the microneedle patch alone both significantly improved the Merz esthetic scales for nasolabial folds. Measurement of the nasolabial fold showed an improvement in the two groups, with no significant differences between the groups. No adverse effects were reported during the study period. CONCLUSIONS: Application of a microneedle patch with 1.8% hyaluronic acid solution or a microneedle patch alone were both effective treatments for improving facial wrinkles in the nasolabial folds.

Transcriptome profiling in psoriasis: NB-UVB treatment-associated transcriptional changes and modulation of autoinflammation in perilesional skin in early-phase disease.

BACKGROUND: Psoriasis is a chronic inflammatory skin condition. It is widely treated with phototherapy using narrowband ultraviolet B (NB-UVB). The therapeutic mechanisms of NB-UVB, however, remain unclear, particularly in the early phases of the disease. OBJECTIVE: To investigate the mechanisms underlying the effects of NB-UVB on psoriasis in a model of perilesional psoriasis. METHODS: Psoriatic patients that received NB-UVB treatment and were evaluated with the psoriasis area and severity index were included in the study. Skin biopsies obtained before and after treatment were subjected to RNA sequencing (RNA-seq) and Ingenuity Pathway Analyses for genome-wide transcriptome profiling to gain further insights into the signaling pathways underlying the improvement of psoriasis with therapeutic intervention. RESULTS: Our findings revealed that NB-UVB treatment may exert its effects by suppressing nuclear factor kappa B, which leads to upregulation of the sirtuin signaling pathway, as well as by decreasing the function of major upstream regulators associated with proinflammatory and inflammatory cytokines, which blocks the expression of downstream toll-like receptors. Psoriasis improvement after NB-UVB treatment was associated with decreased expression of NFKBIZ, SERPINB4, ATG13, and CTSS and increased expression of SKP1 gene. Our results also highlighted the expression of proposed genes associated with the modulation of autoinflammation. CONCLUSIONS: To the best of our knowledge, this is the first study to apply advanced molecular techniques to explore the effects of phototherapy on psoriasis in the early-phase, providing new insights into the disease pathogenesis and novel genetic information for the development of new therapeutic modalities and potential treatment targets.

Comparison of Malassezia spp. colonization between human skin exposed to high- and low-ambient air pollution.

The skin microbiota is essential for human health; altered skin microbiome colonization and homeostasis may be associated with several inflammatory skin conditions and other inflammatory diseases. Malassezia spp. are commensal fungi commonly found on the human skin, and they also play a pathogenic role in various skin diseases. It is hypothesized that the exposure of human skin to air pollution might be associated with Malassezia spp. colonization. The aim of this study was to compare Malassezia spp. colonization on healthy human skin between people living in two major cities in Thailand with different air qualities: one city with highly polluted ambient air and the other with less polluted air. Skin microbiome samples from 66 participants were collected using swabbing and scraping techniques. The skin fungal composition was analysed using high-throughput sequencing based on internal transcribed spacer 2 (ITS2) rDNA. A significant difference was found in alpha and beta diversities and the relative abundance of fungal profiles between the groups. The relative abundance of Malassezia spp. was found to be significantly higher in the highly polluted area than in the less polluted area. This study demonstrates that high-ambient air pollution may alter Malassezia spp. colonization on healthy human skin, which could lead to dysbiosis of the cutaneous ecosystem and eventually result in some skin disorders.

Alteration of gut microbiota during narrowband ultraviolet B therapy in psoriasis: A preliminary study.

Gut microbiome dysbiosis is associated with psoriasis development. A relationship between gut microbiota and psoriasis treatment response has been reported. No study has reported the effect of narrowband ultraviolet B (NBUVB) therapy, a standard treatment of psoriasis, on gut microbiota. This study aimed to evaluate gut microbiota change during NBUVB therapy. Stool samples from 22 participants, including 13 patients with chronic plaque psoriasis and nine healthy controls, were recruited. Faecal microbiota composition was analysed using 16S rRNA sequencing before and after NBUVB therapy. Serum 25-OH vitamin D of patients with psoriasis was evaluated simultaneously. The most abundant phyla of gut microbiota in patients with psoriasis were Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria in all participants. Bilophila, Paraprevotella, Alistipes, Sutterella, Romboutsia, Clostridium sensu stricto and Agathobacter are significantly more enriched in healthy controls. Lactobacillales and Ruminococus torques appeared more enriched after NBUVB treatment in responders but not non-responders. Serum vitamin D levels significantly increased after NBUVB treatment. The present study revealed that gut microbiota altered after NBUVB treatment. The change might be treatment-specific and influence the treatment response.

Transcriptomic Profiling of Peripheral Edge of Lesions to Elucidate the Pathogenesis of Psoriasis Vulgaris.

Elucidating transcriptome in the peripheral edge of the lesional (PE) skin could provide a better understanding of the molecules or signalings that intensify inflammation in the PE skin. Full-thickness biopsies of PE skin and uninvolved (UN) skin were obtained from psoriasis patients for RNA-seq. Several potential differentially expressed genes (DEGs) in the PE skin compared to those in the UN skin were identified. These DEGs enhanced functions such as angiogenesis, growth of epithelial tissue, chemotaxis and homing of cells, growth of connective tissues, and degranulation of myeloid cells beneath the PE skin. Moreover, the canonical pathways of IL-17A, IL-6, and IL-22 signaling were enriched by the DEGs. Finally, we proposed that inflammation in the PE skin might be driven by the IL-36/TLR9 axis or IL-6/Th17 axis and potentiated by IL-36α, IL-36γ, IL-17C, IL-8, S100A7, S100A8, S100A9, S100A15, SERPINB4, and hBD-2. Along with IL-36α, IL-17C, and IκBζ, ROCK2 could be an equally important factor in the pathogenesis of psoriasis, which may involve self-sustaining circuits between innate and adaptive immune responses via regulation of IL-36α and IL-36γ expression. Our finding provides new insight into signaling pathways in PE skin, which could lead to the discovery of new psoriasis targets.

High-Throughput RNA Sequencing Reveals the Effect of NB-UVB Phototherapy on Major Inflammatory Molecules of Lesional Psoriasis.

OBJECTIVE: To identify the narrowband ultraviolet B (NB-UVB)-induced molecular mechanisms that may account for their anti-inflammatory efficacy, gene expression and transcriptome profiling, which were performed using advanced molecular techniques. METHODS: This research was conducted on patients with moderate-to-severe plaque-type psoriasis who received NB-UVB treatment. RNA sequencing (RNA-Seq) was conducted to assay the transcriptomes and identify the differentially expressed transcripts that had been enriched during the major pathway analysis. RESULTS: Clinical improvement of psoriasis by NB-UVB therapy is linked to the suppression of the "immunological signaling pathways" and "cell cycle regulatory, growth and proliferation pathways" which are critical to the pathogenesis of the disease. In addition, these results were further substantiated by demonstrating that NB-UVB therapy has a significant effect on keratinocyte differentiation and affects the regulation of genes and inflammatory mediators that are related to cell proliferation and apoptosis. Moreover, NB-UVB phototherapy is also involved with the downregulation of toll-like receptors signaling in lesional psoriasis. CONCLUSION: NB-UVB is an effective treatment for psoriasis. Our study supports the conclusion that the clinical effectiveness of NB-UVB therapy is based on the suppression of a broad range of inflammatory signaling pathways, gene expression of inflammatory cytokines and increased expressions of anti-inflammatory signaling pathways in psoriatic skin. This is the first study that applied advanced molecular techniques to investigate phototherapy as a new key to unlock genetic knowledge and create novel information. Ultimately, the goal is to increase medical knowledge and improve the patient care of psoriasis.

Down-regulation of miR-155 after treatment with narrow-band UVB and methotrexate associates with apoptosis of keratinocytes in psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease arising from a complex interaction between genetics, epigenetics, the host's immune system and the environment. Recent accumulated data revealed the dysregulation of various microRNAs (miRNAs) in several diseases including psoriasis. OBJECTIVE: We explored the functional role and regulation of hsa-miR-155-5p (miR-155) in an immortalized keratinocyte cell line (HaCaT), in relation to the pathogenesis and treatment of psoriasis. METHODS: miR-155 expression in normal skin and psoriatic skin lesion before and after treatment with methotrexate (MTX) and narrow-band ultraviolet B phototherapy (NB-UVB) were analyzed using quantitative reverse transcription PCR (qRT-PCR). Apoptotic activity, cell cycle and viable cells of miR-155 transfected HaCaT were measured using flow cytometry and MTS assay. Since, caspase-3 (CASP3) gene was predicted as a target gene of miR-155, the expression of CASP3 was detected in transfected HaCaT using western blot. RESULTS: We discovered that both MTX and NB-UVB significantly down-regulated miR-155 expression in psoriatic skin lesions. We also found that overexpression of miR-155 in HaCaT led to suppression of cell apoptosis and induced cell arrest at G0/G1 phase. Moreover, CASP3 expression was down-regulated in miR-155 transfected HaCaT. CONCLUSIONS: This study demonstrates down-regulation of miR155 after treatment with MTX and NB-UVB in psoriatic skin lesion. miR155 plays significant role in apoptosis on HaCaT via CASP3. This finding provides a better understanding of the pathogenesis of psoriasis and might aid on developing the new monitoring tool or therapy for psoriasis in the future.

Comparative Study Of Photodynamic Therapy With Riboflavin-Tryptophan Gel And 13% 5-Aminolevulinic Acid In The Treatment Of Mild To Moderate Acne Vulgaris.

BACKGROUND: Non-invasive photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has been used as an alternative acne treatment for many years. Riboflavin and tryptophan are newly introduced photosensitizers. OBJECTIVE: To compare the efficacy of PDT with riboflavin-tryptophan (RT) gel with that of 13% ALA for the treatment of facial acne. METHODS: We performed a double-blind, split-face study of 37 subjects with mild to moderate facial acne vulgaris. RT gel was applied to half of the face, and 13% ALA was applied to the other half. Then, the whole face was irradiated using a blue light-emitting diode for 20 mins. Four treatment sessions were performed over a 4-week duration, at 1-week interval. The acne lesion counts and acne severity were assessed. Sebum secretion, Propionibacterium acne colonization, pore size, and skin texture were also evaluated. RESULTS: PDT with RT gel demonstrated good efficacy, non-inferior to ALA for acne treatment, with a significant reduction in acne lesion counts, severity grading, porphyrin, and sebum output. The pore size and skin texture were improved. Side-effects were minimal and well tolerated in all subjects. CONCLUSION: PDT therapy with RT gel is an effective alternative treatment for acne vulgaris.

Anti-inflammatory effect of naringin and sericin combination on human peripheral blood mononuclear cells (hPBMCs) from patient with psoriasis.

BACKGROUND: Several immunological pathways, particularly skin inflammation via various pro-inflammatory cytokines have been reported to be involved in the pathogenesis and clinical manifestations of psoriasis. The aim of the study was to investigate the potential role of naringin from Citrus maxima (Burm.) Merr and sericin from Bombyx mori combination in the treatment of psoriasis. Inhibitory effects on the expression of mRNA and the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-23, and IL-12p40) were investigated. METHODS: Human peripheral blood mononuclear cells (hPBMCs) were isolated from 10 healthy subjects and 10 patients with psoriasis. The hPBMCs from each group were exposed to naringin or sericin alone, and the combination of naringin and sericin. The expression levels of mRNA and the production of all cytokines were determined using quantitative RT-PCR and ELISA, respectively. RESULTS: Naringin/sericin combination significantly decreased the expression of mRNA and the production of all pro-inflammatory cytokines in hPBMCs from patients with psoriasis. The potency of inhibitory activity was markedly higher than naringin or sericin alone. CONCLUSION: The activity of naringin/sericin combination on down-regulation of these pro-inflammatory cytokines suggested its potential clinical use in psoriasis as well as other inflammation-associated diseases. The combination might be used as a complementary therapy with conventional treatment in psoriasis to improve clinical efficacy and tolerability.

Development of a Global Subjective Skin Aging Assessment score from the perspective of dermatologists.

OBJECTIVE: Several skin aging assessment scales exist but no standard scale is widely used. Dermatologists may be the most appropriate persons for skin assessment but their perceptions regarding the signs of skin aging are unexplored. To develop a simple global skin aging assessment score from the perspective of dermatologists, an online questionnaire, the Thai Dermatologist Survey of Skin Aging Assessment, was conducted from October to December, 2016. Twenty-nine signs with published evidence of their relevancy to skin aging were included. Certified dermatologists were asked to score each sign using a 5-point Likert scale. Descriptive statistics and exploratory factor analysis (EFA) were used for data analysis. RESULTS: Of 213 randomly selected dermatologists, 145 responded to the survey. EFA revealed 3 important factors related to skin aging: Factor 1 comprised 8 signs related to atrophy (deep/superficial wrinkles, eye bags, lax appearance, etc.); Factor 2 comprised 7 signs related to discoloration (freckles, lentigines, melasma, etc.); and Factor 3 comprised 3 malignant skin lesions. The Global Subjective Skin Aging Assessment (GS2A2) score is a simple numerical score that can be used to evaluate the anti-aging effects of a cosmetic product or dermatologic intervention. This score should be tested further for validity and reliability.