ABSTRACT
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.
Subject(s)
Alopecia , Hair Follicle , Male , Animals , Mice , Mice, Inbred C57BL , Alopecia/drug therapy , Hair Follicle/pathology , Skin/pathology , ScalpABSTRACT
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.
Subject(s)
Psoriasis , Sirtuins , Ultraviolet Therapy , Cytokines , Gene Expression Profiling , Humans , NF-kappa B , Psoriasis/drug therapy , Psoriasis/genetics , Psoriasis/radiotherapy , Ultraviolet Therapy/methodsABSTRACT
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.
Subject(s)
Gastrointestinal Microbiome , Psoriasis , Ultraviolet Therapy , Bacteroidetes , Dysbiosis , Humans , Psoriasis/radiotherapy , RNA, Ribosomal, 16S/genetics , Vitamin DABSTRACT
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.
ABSTRACT
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.
Subject(s)
MicroRNAs , Psoriasis , Ultraviolet Therapy , Apoptosis/genetics , Cell Proliferation , Down-Regulation , Humans , Keratinocytes , Methotrexate/pharmacology , MicroRNAs/genetics , Psoriasis/drug therapy , Psoriasis/geneticsSubject(s)
Alopecia Areata/therapy , Phototherapy/instrumentation , Adult , Female , Humans , Male , Middle AgedABSTRACT
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.